''Iatrogenic Gilbert syndrome''- A strategy for reducing vascular and cancer risk by increasing plasma unconjugated bilirubin

Medical Hypotheses

Volumn 69, Issue 5, 2007, Pages 974-994

  McCarty, Mark F ^a  

^a Oasis of Hope Hospital   (Mexico)

Author keywords

[No Author keywords available]

Indexed keywords

BILIRUBIN; BILIVERDIN; C REACTIVE PROTEIN; GLUCURONIC ACID; GLUCURONOSYLTRANSFERASE; HEME OXYGENASE 1; PROBENECID; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE PHOSPHATE OXIDASE; RIFAMPICIN;

ANTIOXIDANT ACTIVITY; ARTICLE; ATHEROGENESIS; BILIRUBIN BINDING; BILIRUBIN BLOOD LEVEL; CANCER RISK; DIFFERENTIAL DIAGNOSIS; DRUG MECHANISM; GENETIC DISORDER; GILBERT DISEASE; HUMAN; HYPERBILIRUBINEMIA; HYPERTENSION; IATROGENIC DISEASE; ISCHEMIC HEART DISEASE; PRIORITY JOURNAL; PROGNOSIS; PROTEIN EXPRESSION; PROTEIN TARGETING; RISK FACTOR; VASCULAR DISEASE;

ANIMALS; BILIRUBIN; GILBERT DISEASE; HUMANS; MODELS, BIOLOGICAL; NEOPLASMS; RISK REDUCTION BEHAVIOR; SYNDROME; VASCULAR DISEASES;

ALGAE; RODENTIA;

EID: 34548761301     PISSN: 03069877     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.mehy.2006.12.069     Document Type: Article

References (311)

1. Morse D., and Choi A.M. Heme oxygenase-1: the ''emerging molecule'' has arrived. Am J Respir Cell Mol Biol 27 (2002) 8-16
2. Otterbein L.E., Soares M.P., Yamashita K., and Bach F.H. Heme oxygenase-1: unleashing the protective properties of heme. Trends Immunol 24 (2003) 449-455
3. Shibahara S. The heme oxygenase dilemma in cellular homeostasis: new insights for the feedback regulation of heme catabolism. Tohoku J Exp Med 200 (2003) 167-186
4. Alam J., Igarashi K., Immenschuh S., Shibahara S., and Tyrrell R.M. Regulation of heme oxygenase-1 gene transcription: recent advances and highlights from the International Conference (Uppsala, 2003) on Heme Oxygenase. Antioxid Redox Signal 6 (2004) 924-933
5. Stocker R., Yamamoto Y., McDonagh A.F., Glazer A.N., and Ames B.N. Bilirubin is an antioxidant of possible physiological importance. Science 235 (1987) 1043-1046
6. Stocker R., and Peterhans E. Antioxidant properties of conjugated bilirubin and biliverdin: biologically relevant scavenging of hypochlorous acid. Free Radic Res Commun 6 (1989) 57-66
7. Wagner J.R., Motchnik P.A., Stocker R., Sies H., and Ames B.N. The oxidation of blood plasma and low density lipoprotein components by chemically generated singlet oxygen. J Biol Chem 268 (1993) 18502-18506
8. Farrera J.A., Jauma A., Ribo J.M., Peire M.A., Parellada P.P., Roques-Choua S., et al. The antioxidant role of bile pigments evaluated by chemical tests. Bioorg Med Chem 2 (1994) 181-185
9. Kaur H., Hughes M.N., Green C.J., Naughton P., Foresti R., and Motterlini R. Interaction of bilirubin and biliverdin with reactive nitrogen species. FEBS Lett 543 (2003) 113-119
10. Stocker R. Antioxidant activities of bile pigments. Antioxid Redox Signal 6 (2004) 841-849
11. Wakabayashi N., Dinkova-Kostova A.T., Holtzclaw W.D., Kang M.I., Kobayashi A., Yamamoto M., et al. Protection against electrophile and oxidant stress by induction of the phase 2 response: fate of cysteines of the Keap1 sensor modified by inducers. Proc Natl Acad Sci USA 101 (2004) 2040-2045
12. Itoh K., Tong K.I., and Yamamoto M. Molecular mechanism activating Nrf2-Keap1 pathway in regulation of adaptive response to electrophiles. Free Radic Biol Med 36 (2004) 1208-1213
13. Otterbein L.E., and Choi A.M. Heme oxygenase: colors of defense against cellular stress. Am J Physiol Lung Cell Mol Physiol 279 (2000) L1029-L1037
14. Foresti R., Sarathchandra P., Clark J.E., Green C.J., and Motterlini R. Peroxynitrite induces haem oxygenase-1 in vascular endothelial cells: a link to apoptosis. Biochem J 339 Pt 3 (1999) 729-736
15. Olszanecki R., and Marcinkiewicz J. Taurine chloramine and taurine bromamine induce heme oxygenase-1 in resting and LPS-stimulated J774.2 macrophages. Amino Acids 27 (2004) 29-35
16. Polte T., Abate A., Dennery P.A., and Schroder H. Heme oxygenase-1 is a cGMP-inducible endothelial protein and mediates the cytoprotective action of nitric oxide. Arterioscler Thromb Vasc Biol 20 (2000) 1209-1215
17. Grosser N., Hemmerle A., Berndt G., Erdmann K., Hinkelmann U., Schurgerc S., et al. The antioxidant defense protein heme oxygenase 1 is a novel target for statins in endothelial cells. Free Radic Biol Med 37 (2004) 2064-2071
18. Grosser N., Erdmann K., Hemmerle A., Berndt G., Hinkelmann U., Smith G., et al. Rosuvastatin upregulates the antioxidant defense protein heme oxygenase-1. Biochem Biophys Res Commun 325 (2004) 871-876
19. Grosser N., Oberle S., Berndt G., Erdmann K., Hemmerle A., and Schroder H. Antioxidant action of l-alanine: heme oxygenase-1 and ferritin as possible mediators. Biochem Biophys Res Commun 314 (2004) 351-355
20. Deng Y.M., Wu B.J., Witting P.K., and Stocker R. Probucol protects against smooth muscle cell proliferation by upregulating heme oxygenase-1. Circulation 110 (2004) 1855-1860
21. Acquaviva R., Campisi A., Murabito P., Raciti G., Avola R., Mangiameli S., et al. Propofol attenuates peroxynitrite-mediated DNA damage and apoptosis in cultured astrocytes: an alternative protective mechanism. Anesthesiology 101 (2004) 1363-1371
22. Calabrese V, Ravagna A, Colombrita C, Scapagnini G, Guagliano E, Calvani M, et al. Acetylcarnitine induces heme oxygenase in rat astrocytes and protects against oxidative stress: involvement of the transcription factor Nrf2. J Neurosci Res 2005.
23. Sarady J.K., Otterbein S.L., Liu F., Otterbein L.E., and Choi A.M. Carbon monoxide modulates endotoxin-induced production of granulocyte macrophage colony-stimulating factor in macrophages. Am J Respir Cell Mol Biol 27 (2002) 739-745
24. Schmidt H.H. NO., CO and .OH. Endogenous soluble guanylyl cyclase-activating factors. FEBS Lett 307 (1992) 102-107
25. Stone J.R., and Marletta M.A. Synergistic activation of soluble guanylate cyclase by YC-1 and carbon monoxide: implications for the role of cleavage of the iron-histidine bond during activation by nitric oxide. Chem Biol 5 (1998) 255-261
26. Imai T., Morita T., Shindo T., Nagai R., Yazaki Y., Kurihara H., et al. Vascular smooth muscle cell-directed overexpression of heme oxygenase-1 elevates blood pressure through attenuation of nitric oxide-induced vasodilation in mice. Circ Res 89 (2001) 55-62
27. Johnson F.K., Durante W., Peyton K.J., and Johnson R.A. Heme oxygenase inhibitor restores arteriolar nitric oxide function in dahl rats. Hypertension 41 (2003) 149-155
28. Ndisang J.F., Tabien H.E., and Wang R. Carbon monoxide and hypertension. J Hypertens 22 (2004) 1057-1074
29. Ishikawa K., Navab M., Leitinger N., Fogelman A.M., and Lusis A.J. Induction of heme oxygenase-1 inhibits the monocyte transmigration induced by mildly oxidized LDL. J Clin Invest 100 (1997) 1209-1216
30. Yoshida T., Maulik N., Ho Y.S., Alam J., and Das D.K. H(mox-1) constitutes an adaptive response to effect antioxidant cardioprotection: a study with transgenic mice heterozygous for targeted disruption of the Heme oxygenase-1 gene. Circulation 103 (2001) 1695-1701
31. Mazza F., Goodman A., Lombardo G., Vanella A., and Abraham N.G. Heme oxygenase-1 gene expression attenuates angiotensin II-mediated DNA damage in endothelial cells. Exp Biol Med (Maywood) 228 (2003) 576-583
32. Zhang X., Shan P., Jiang D., Noble P.W., Abraham N.G., Kappas A., et al. Small interfering RNA targeting heme oxygenase-1 enhances ischemia-reperfusion-induced lung apoptosis. J Biol Chem 279 (2004) 10677-10684
33. Quan S., Kaminski P.M., Yang L., Morita T., Inaba M., Ikehara S., et al. Heme oxygenase-1 prevents superoxide anion-associated endothelial cell sloughing in diabetic rats. Biochem Biophys Res Commun 315 (2004) 509-516
34. Baranano D.E., Rao M., Ferris C.D., and Snyder S.H. Biliverdin reductase: a major physiologic cytoprotectant. Proc Natl Acad Sci USA 99 (2002) 16093-16098
35. Sedlak T.W., and Snyder S.H. Bilirubin benefits: cellular protection by a biliverdin reductase antioxidant cycle. Pediatrics 113 (2004) 1776-1782
36. Juan S.H., Lee T.S., Tseng K.W., Liou J.Y., Shyue S.K., Wu K.K., et al. Adenovirus-mediated heme oxygenase-1 gene transfer inhibits the development of atherosclerosis in apolipoprotein E-deficient mice. Circulation 104 (2001) 1519-1525
37. Ishikawa K., Sugawara D., Wang X., Suzuki K., Itabe H., Maruyama Y., et al. Heme oxygenase-1 inhibits atherosclerotic lesion formation in ldl-receptor knockout mice. Circ Res 88 (2001) 506-512
38. Ishikawa K., Sugawara D., Goto J., Watanabe Y., Kawamura K., Shiomi M., et al. Heme oxygenase-1 inhibits atherogenesis in Watanabe heritable hyperlipidemic rabbits. Circulation 104 (2001) 1831-1836
39. Lindenblatt N., Bordel R., Schareck W., Menger M.D., and Vollmar B. Vascular heme oxygenase-1 induction suppresses microvascular thrombus formation in vivo. Arterioscler Thromb Vasc Biol 24 (2004) 601-606
40. Peng L., Mundada L., Stomel J.M., Liu J.J., Sun J., Yet S.F., et al. Induction of heme oxygenase-1 expression inhibits platelet-dependent thrombosis. Antioxid Redox Signal 6 (2004) 729-735
41. Agarwal A., and Nick H.S. Renal response to tissue injury: lessons from heme oxygenase-1 GeneAblation and expression. J Am Soc Nephrol 11 (2000) 965-973
42. Bauer M., and Bauer I. Heme oxygenase-1: redox regulation and role in the hepatic response to oxidative stress. Antioxid Redox Signal 4 (2002) 749-758
43. Li L., Grenard P., Nhieu J.T., Julien B., Mallat A., Habib A., et al. Heme oxygenase-1 is an antifibrogenic protein in human hepatic myofibroblasts. Gastroenterology 125 (2003) 460-469
44. Nakahira K., Takahashi T., Shimizu H., Maeshima K., Uehara K., Fujii H., et al. Protective role of heme oxygenase-1 induction in carbon tetrachloride-induced hepatotoxicity. Biochem Pharmacol 66 (2003) 1091-1105
45. Liu L.G., Yan H., Zhang W., Yao P., Zhang X.P., Sun X.F., et al. Induction of heme oxygenase-1 in human hepatocytes to protect them from ethanol-induced cytotoxicity. Biomed Environ Sci 17 (2004) 315-326
46. Suttner D.M., Sridhar K., Lee C.S., Tomura T., Hansen T.N., and Dennery P.A. Protective effects of transient HO-1 overexpression on susceptibility to oxygen toxicity in lung cells. Am J Physiol 276 (1999) L443-L451
47. Otterbein L.E., Kolls J.K., Mantell L.L., Cook J.L., Alam J., and Choi A.M. Exogenous administration of heme oxygenase-1 by gene transfer provides protection against hyperoxia-induced lung injury. J Clin Invest 103 (1999) 1047-1054
48. Li L., Hamilton Jr. R.F., and Holian A. Protection against ozone-induced pulmonary inflammation and cell death by endotoxin pretreatment in mice: role of HO-1. Inhal Toxicol 12 (2000) 1225-1238
49. Clark J.E., Foresti R., Sarathchandra P., Kaur H., Green C.J., and Motterlini R. Heme oxygenase-1-derived bilirubin ameliorates postischemic myocardial dysfunction. Am J Physiol Heart Circ Physiol 278 (2000) H643-H651
50. Hangaishi M., Ishizaka N., Aizawa T., Kurihara Y., Taguchi J., Nagai R., et al. Induction of heme oxygenase-1 can act protectively against cardiac ischemia/reperfusion in vivo. Biochem Biophys Res Commun 279 (2000) 582-588
51. Masini E., Vannacci A., Marzocca C., Pierpaoli S., Giannini L., Fantappie O., et al. Heme oxygenase-1 and the ischemia-reperfusion injury in the rat heart. Exp Biol Med (Maywood) 228 (2003) 546-549
52. Attuwaybi B.O., Kozar R.A., Moore-Olufemi S.D., Sato N., Hassoun H.T., Weisbrodt N.W., et al. Heme oxygenase-1 induction by hemin protects against gut ischemia/reperfusion injury. J Surg Res 118 (2004) 53-57
53. Chen Y.H., Yet S.F., and Perrella M.A. Role of heme oxygenase-1 in the regulation of blood pressure and cardiac function. Exp Biol Med (Maywood) 228 (2003) 447-453
54. Hu C.M., Chen Y.H., Chiang M.T., and Chau L.Y. Heme oxygenase-1 inhibits angiotensin II-induced cardiac hypertrophy in vitro and in vivo. Circulation 110 (2004) 309-316
55. Yet S.F., Layne M.D., Liu X., Chen Y.H., Ith B., Sibinga N.E., et al. Absence of heme oxygenase-1 exacerbates atherosclerotic lesion formation and vascular remodeling. FASEB J 17 (2003) 1759-1761
56. Hayashi S., Takamiya R., Yamaguchi T., Matsumoto K., Tojo S.J., Tamatani T., et al. Induction of heme oxygenase-1 suppresses venular leukocyte adhesion elicited by oxidative stress: role of bilirubin generated by the enzyme. Circ Res 85 (1999) 663-671
57. Vachharajani T.J., Work J., Issekutz A.C., and Granger D.N. Heme oxygenase modulates selectin expression in different regional vascular beds. Am J Physiol Heart Circ Physiol 278 (2000) H1613-H1617
58. Soares M.P., Seldon M.P., Gregoire I.P., Vassilevskaia T., Berberat P.O., Yu J., et al. Heme oxygenase-1 modulates the expression of adhesion molecules associated with endothelial cell activation. J Immunol 172 (2004) 3553-3563
59. Kawamura K., Ishikawa K., Wada Y., Kimura S., Matsumoto H., Kohro T., et al. Bilirubin from heme oxygenase-1 attenuates vascular endothelial activation and dysfunction. Arterioscler Thromb Vasc Biol 25 (2005) 155-160
60. Kimpara T., Takeda A., Watanabe K., Itoyama Y., Ikawa S., Watanabe M., et al. Microsatellite polymorphism in the human heme oxygenase-1 gene promoter and its application in association studies with Alzheimer and Parkinson disease. Hum Genet 100 (1997) 145-147
61. Yamada N., Yamaya M., Okinaga S., Nakayama K., Sekizawa K., Shibahara S., et al. Microsatellite polymorphism in the heme oxygenase-1 gene promoter is associated with susceptibility to emphysema. Am J Hum Genet 66 (2000) 187-195
62. Chen Y.H., Lin S.J., Lin M.W., Tsai H.L., Kuo S.S., Chen J.W., et al. Microsatellite polymorphism in promoter of heme oxygenase-1 gene is associated with susceptibility to coronary artery disease in type 2 diabetic patients. Hum Genet 111 (2002) 1-8
63. Naylor L.H., and Clark E.M. d(TG)n.d(CA)n sequences upstream of the rat prolactin gene form Z-DNA and inhibit gene transcription. Nucleic Acids Res 18 (1990) 1595-1601
64. Exner M., Minar E., Wagner O., and Schillinger M. The role of heme oxygenase-1 promoter polymorphisms in human disease. Free Radic Biol Med 37 (2004) 1097-1104
65. Kikuchi A, Yamaya M, Suzuki S, Yasuda H, Kubo H, Nakayama K, et al. Association of susceptibility to the development of lung adenocarcinoma with the heme oxygenase-1 gene promoter polymorphism. Hum Genet 2005.
66. Endler G., Exner M., Schillinger M., Marculescu R., Sunder-Plassmann R., Raith M., et al. A microsatellite polymorphism in the heme oxygenase-1 gene promoter is associated with increased bilirubin and HDL levels but not with coronary artery disease. Thromb Haemost 91 (2004) 155-161
67. Yamaya M., Nakayama K., Ebihara S., Hirai H., Higuchi S., and Sasaki H. Relationship between microsatellite polymorphism in the haem oxygenase-1 gene promoter and longevity of the normal Japanese population. J Med Genet 40 (2003) 146-148
68. Schwertner H.A., Jackson W.G., and Tolan G. Association of low serum concentration of bilirubin with increased risk of coronary artery disease. Clin Chem 40 (1994) 18-23
69. Novotny L., and Vitek L. Inverse relationship between serum bilirubin and atherosclerosis in men: a meta-analysis of published studies. Exp Biol Med (Maywood) 228 (2003) 568-571
70. Breimer L.H., Wannamethee G., Ebrahim S., and Shaper A.G. Serum bilirubin and risk of ischemic heart disease in middle-aged British men. Clin Chem 41 (1995) 1504-1508
71. Temme E.H., Zhang J., Schouten E.G., and Kesteloot H. Serum bilirubin and 10-year mortality risk in a Belgian population. Cancer Causes Control 12 (2001) 887-894
72. Zucker S.D., Horn P.S., and Sherman K.E. Serum bilirubin levels in the U.S. population: gender effect and inverse correlation with colorectal cancer. Hepatology 40 (2004) 827-835
73. Ko W.F., Helzlsouer K.J., and Comstock G.W. Serum albumin, bilirubin, and uric acid and the anatomic site-specific incidence of colon cancer. J Natl Cancer Inst 86 (1994) 1874-1875
74. Ching S., Ingram D., Hahnel R., Beilby J., and Rossi E. Serum levels of micronutrients, antioxidants and total antioxidant status predict risk of breast cancer in a case control study. J Nutr 132 (2002) 303-306
75. Chang K.W., Lee T.C., Yeh W.I., Chung M.Y., Liu C.J., Chi L.Y., et al. Polymorphism in heme oxygenase-1 (HO-1) promoter is related to the risk of oral squamous cell carcinoma occurring on male areca chewers. Br J Cancer 91 (2004) 1551-1555
76. Brodersen R. Binding of bilirubin to albumin. CRC Crit Rev Clin Lab Sci 11 (1980) 305-399
77. Weisiger R.A., Ostrow J.D., Koehler R.K., Webster C.C., Mukerjee P., Pascolo L., et al. Affinity of human serum albumin for bilirubin varies with albumin concentration and buffer composition: results of a novel ultrafiltration method. J Biol Chem 276 (2001) 29953-29960
78. Ostrow J.D., Pascolo L., Shapiro S.M., and Tiribelli C. New concepts in bilirubin encephalopathy. Eur J Clin Invest 33 (2003) 988-997
79. Zucker S.D., Goessling W., and Hoppin A.G. Unconjugated bilirubin exhibits spontaneous diffusion through model lipid bilayers and native hepatocyte membranes. J Biol Chem 274 (1999) 10852-10862
80. Ko G.T., Chan J.C., Woo J., Lau E., Yeung V.T., Chow C.C., et al. Serum bilirubin and cardiovascular risk factors in a Chinese population. J Cardiovasc Risk 3 (1996) 459-463
81. Madhavan M., Wattigney W.A., Srinivasan S.R., and Berenson G.S. Serum bilirubin distribution and its relation to cardiovascular risk in children and young adults. Atherosclerosis 131 (1997) 107-113
82. Torgerson J.S., Lindroos A.K., Sjostrom C.D., Olsson R., Lissner L., and Sjostrom L. Are elevated aminotransferases and decreased bilirubin additional characteristics of the metabolic syndrome?. Obes Res 5 (1997) 105-114
83. Canepa E.T., Llambias E.B., and Grinstein M. Studies on regulatory mechanisms of heme biosynthesis in hepatocytes from normal and experimental-diabetic rats. Role of insulin. Biochem Cell Biol 68 (1990) 914-921
84. Bosma P.J., Chowdhury J.R., Bakker C., Gantla S., de Boer A., Oostra B.A., et al. The genetic basis of the reduced expression of bilirubin UDP-glucuronosyltransferase 1 in Gilbert's syndrome. N Engl J Med 333 (1995) 1171-1175
85. Seppen J., Bosma P.J., Goldhoorn B.G., Bakker C.T., Chowdhury J.R., Chowdhury N.R., et al. Discrimination between Crigler-Najjar type I and II by expression of mutant bilirubin uridine diphosphate-glucuronosyltransferase. J Clin Invest 94 (1994) 2385-2391
86. Vitek L., Jirsa M., Brodanova M., Kalab M., Marecek Z., Danzig V., et al. Gilbert syndrome and ischemic heart disease: a protective effect of elevated bilirubin levels. Atherosclerosis 160 (2002) 449-456
87. Pflueger A., Croatt A.J., Peterson T.E., Smith L.A., d'Uscio L.V., Katusic Z.S., et al. The hyperbilirubinemic gunn rat is resistant to the pressor effects of angiotensin II. Am J Physiol Renal Physiol (2004)
88. Belanger S., Lavoie J.C., and Chessex P. Influence of bilirubin on the antioxidant capacity of plasma in newborn infants. Biol Neonate 71 (1997) 233-238
89. Alvarez B., and Radi R. Peroxynitrite reactivity with amino acids and proteins. Amino Acids 25 (2003) 295-311
90. Minetti M., Mallozzi C., Di Stasi A.M., and Pietraforte D. Bilirubin is an effective antioxidant of peroxynitrite-mediated protein oxidation in human blood plasma. Arch Biochem Biophys 352 (1998) 165-174
91. Bokoch G.M., and Knaus U.G. NADPH oxidases: not just for leukocytes anymore!. Trends Biochem Sci 28 (2003) 502-508
92. Nakagawara A., Inokuchi K., Ikeda K., Kumashiro R., and Tamada R. Decreased superoxide (O2-)-generating activity of blood monocytes from patients with hepatic cirrhosis. Hepatogastroenterology 31 (1984) 201-203
93. Iwanaga M., Nakagawara A., Matsuo S., and Ikeda K. Impaired polymorphonuclear leukocyte function in biliary atresia: role of bilirubin and bile acids. J Pediatr Surg 22 (1987) 967-972
94. Nakamura H., Uetani Y., Komura M., Takada S., Sano K., and Matsuo T. Inhibitory action of bilirubin on superoxide production by polymorphonuclear leukocytes. Biol Neonate 52 (1987) 273-278
95. Taille C., Almolki A., Benhamed M., Zedda C., Megret J., Berger P., et al. Heme oxygenase inhibits human airway smooth muscle proliferation via a bilirubin-dependent modulation of ERK1/2 phosphorylation. J Biol Chem 278 (2003) 27160-27168
96. Samb A., Taille C., Almolki A., Megret J., Staddon J.M., Aubier M., et al. Heme oxygenase modulates oxidant-signaled airway smooth muscle contractility: role of bilirubin. Am J Physiol Lung Cell Mol Physiol 283 (2002) L596-L603
97. Taille C., el Benna J., Lanone S., Dang M.C., Ogier-Denis E., Aubier M., et al. Induction of heme oxygenase-1 inhibits NAD(P)H oxidase activity by down-regulating cytochrome b558 expression via the reduction of heme availability. J Biol Chem 279 (2004) 28681-28688
98. Morita T., Imai T., Yamaguchi T., Sugiyama T., Katayama S., and Yoshino G. Induction of heme oxygenase-1 in monocytes suppresses angiotensin II-elicited chemotactic activity through inhibition of CCR2: role of bilirubin and carbon monoxide generated by the enzyme. Antioxid Redox Signal 5 (2003) 439-447
99. Pflueger A., Croatt A.J., Peterson T.E., Smith L.A., d'Uscio L.V., Katusic Z.S., et al. The hyperbilirubinemic Gunn rat is resistant to the pressor effects of angiotensin II. Am J Physiol Renal Physiol 288 (2005) F552-F558
100. Berndt G., Grosser N., Hoogstraate J., and Schroder H. AZD3582 increases heme oxygenase-1 expression and antioxidant activity in vascular endothelial and gastric mucosal cells. Eur J Pharm Sci 25 (2005) 229-235
101. Keshavan P., Deem T.L., Schwemberger S.J., Babcock G.F., Cook-Mills J.M., and Zucker S.D. Unconjugated bilirubin inhibits VCAM-1-mediated transendothelial leukocyte migration. J Immunol 174 (2005) 3709-3718
102. Lanone S., Bloc S., Foresti R., Almolki A., Taille C., Callebert J., et al. Bilirubin decreases NOS2 expression via inhibition of NAD(P)H oxidase: implications for protection against endotoxic shock in rats. FASEB J (2005)
103. Kwak J.Y., Takeshige K., Cheung B.S., and Minakami S. Bilirubin inhibits the activation of superoxide-producing NADPH oxidase in a neutrophil cell-free system. Biochim Biophys Acta 1076 (1991) 369-373
104. Matsumoto H., Ishikawa K., Itabe H., and Maruyama Y. Carbon monoxide and bilirubin from heme oxygenase-1 suppresses reactive oxygen species generation and plasminogen activator inhibitor-1 induction. Mol Cell Biochem 291 (2006) 21-28
105. Jiang F., Roberts S.J., Datla S., and Dusting G.J. NO modulates NADPH oxidase function via heme oxygenase-1 in human endothelial cells. Hypertension 48 (2006) 950-957
106. Taille C., el Benna J., Lanone S., Boczkowski J., and Motterlini R. Mitochondrial respiratory chain and NAD(P)H oxidase are targets for the antiproliferative effect of carbon monoxide in human airway smooth muscle. J Biol Chem 280 (2005) 25350-25360
107. Haga Y., Tempero M.A., and Zetterman R.K. Unconjugated bilirubin inhibits in vitro cytotoxic T lymphocyte activity of human lymphocytes. Biochim Biophys Acta 1317 (1996) 65-70
108. Haga Y., Tempero M.A., Kay D., and Zetterman R.K. Intracellular accumulation of unconjugated bilirubin inhibits phytohemagglutin-induced proliferation and interleukin-2 production of human lymphocytes. Dig Dis Sci 41 (1996) 1468-1474
109. Simon B.C., Haudenschild C.C., and Cohen R.A. Preservation of endothelium-dependent relaxation in atherosclerotic rabbit aorta by probucol. J Cardiovasc Pharmacol 21 (1993) 893-901
110. Plane F., Jacobs M., McManus D., and Bruckdorfer K.R. Probucol and other antioxidants prevent the inhibition of endothelium-dependent relaxation by low density lipoproteins. Atherosclerosis 103 (1993) 73-79
111. Keaney Jr. J.F., Xu A., Cunningham D., Jackson T., Frei B., and Vita J.A. Dietary probucol preserves endothelial function in cholesterol-fed rabbits by limiting vascular oxidative stress and superoxide generation. J Clin Invest 95 (1995) 2520-2529
112. Hoshida S., Yamashita N., Igarashi J., Aoki K., Kuzuya T., and Hori M. Long-term probucol treatment reverses the severity of myocardial injury in watanabe heritable hyperlipidemic rabbits. Arterioscler Thromb Vasc Biol 17 (1997) 2801-2807
113. Jiang J.L., Li Ns N.S., Li Y.J., and Deng H.W. Probucol preserves endothelial function by reduction of the endogenous nitric oxide synthase inhibitor level. Br J Pharmacol 135 (2002) 1175-1182
114. Tagawa T., Urabe Y., Kimura Y., Suzuki S., Ono H., and Takeda K. Long-term treatment with probucol improves endothelial function in patients with coronary artery disease. Hypertens Res 27 (2004) 311-318
115. Vitek L., and Carey M.C. Enterohepatic cycling of bilirubin as a cause of 'black' pigment gallstones in adult life. Eur J Clin Invest 33 (2003) 799-810
116. Nakagami T., Toyomura K., Kinoshita T., and Morisawa S. A beneficial role of bile pigments as an endogenous tissue protector: anti-complement effects of biliverdin and conjugated bilirubin. Biochim Biophys Acta 1158 (1993) 189-193
117. Yamashita K., McDaid J., Ollinger R., Tsui T.Y., Berberat P.O., Usheva A., et al. Biliverdin, a natural product of heme catabolism, induces tolerance to cardiac allografts. FASEB J 18 (2004) 765-767
118. Meyer U.A. Heme biosynthesis. Schweiz Med Wochenschr 105 (1975) 1165-1168
119. Brown S.B., Houghton J.D., and Vernon D.I. Biosynthesis of phycobilins. Formation of the chromophore of phytochrome, phycocyanin and phycoerythrin. J Photochem Photobiol B 5 (1990) 3-23
120. Romay C., Armesto J., Remirez D., Gonzalez R., Ledon N., and Garcia I. Antioxidant and anti-inflammatory properties of C-phycocyanin from blue-green algae. Inflamm Res 47 (1998) 36-41
121. Romay C., and Gonzalez R. Phycocyanin is an antioxidant protector of human erythrocytes against lysis by peroxyl radicals. J Pharm Pharmacol 52 (2000) 367-368
122. Lissi E.A., Pizarro M., Aspee A., and Romay C. Kinetics of phycocyanine bilin groups destruction by peroxyl radicals. Free Radic Biol Med 28 (2000) 1051-1055
123. Bhat V.B., and Madyastha K.M. C-phycocyanin: a potent peroxyl radical scavenger in vivo and in vitro. Biochem Biophys Res Commun 275 (2000) 20-25
124. Bhat V.B., and Madyastha K.M. Scavenging of peroxynitrite by phycocyanin and phycocyanobilin from Spirulina platensis: protection against oxidative damage to DNA. Biochem Biophys Res Commun 285 (2001) 262-266
125. Pinero Estrada J.E., Bermejo B.P., and Villar del Fresno A.M. Antioxidant activity of different fractions of Spirulina platensis protean extract. Farmaco 56 (2001) 497-500
126. Benedetti S., Benvenuti F., Pagliarani S., Francogli S., Scoglio S., and Canestrari F. Antioxidant properties of a novel phycocyanin extract from the blue-green alga Aphanizomenon flos-aquae. Life Sci 75 (2004) 2353-2362
127. Terry M.J., Maines M.D., and Lagarias J.C. Inactivation of phytochrome- and phycobiliprotein-chromophore precursors by rat liver biliverdin reductase. J Biol Chem 268 (1993) 26099-26106
128. Remirez D., Gonzalez R., Merino N., Rodriguez S., and Ancheta O. Inhibitory effects of Spirulina in zymosan-induced arthritis in mice. Mediators Inflamm 11 (2002) 75-79
129. Upasani C.D., and Balaraman R. Protective effect of Spirulina on lead induced deleterious changes in the lipid peroxidation and endogenous antioxidants in rats. Phytother Res 17 (2003) 330-334
130. Romay C., Gonzalez R., Ledon N., Remirez D., and Rimbau V. C-phycocyanin: a biliprotein with antioxidant, anti-inflammatory and neuroprotective effects. Curr Protein Pept Sci 4 (2003) 207-216
131. Remirez D., Ledon N., and Gonzalez R. Role of histamine in the inhibitory effects of phycocyanin in experimental models of allergic inflammatory response. Mediators Inflamm 11 (2002) 81-85
132. Romay C., Delgado R., Remirez D., Gonzalez R., and Rojas A. Effects of phycocyanin extract on tumor necrosis factor-alpha and nitrite levels in serum of mice treated with endotoxin. Arzneimittelforschung 51 (2001) 733-736
133. Troxler R.F., and Bogorad L. Studies on the formation of phycocyanin, porphyrins, and a blue phycobilin by wild-type and mutant strains of Cyanidium caldarium. Plant Physiol 41 (1966) 491-499
134. Fujita Y., and Hattori A. Preliminary note on a new phycobilin pigment isolated from blue-green algae. J Biochem (Tokyo) 51 (1962) 89-91
135. O Carra P., and O hEocha C. Bilins released from algae and biliproteins by methanolic extraction. Phytochemistry 5 (1966) 993-997
136. Bishop J.E., Lagarias J.C., Nagy J.O., Schoenleber R.W., Rapoport H., Klotz A.V., et al. Phycobiliprotein-bilin linkage diversity. I. Structural studies on A- and D-ring-linked phycocyanobilins. J Biol Chem 261 (1986) 6790-6796
137. Patel A., Mishra S., Pawar R., and Ghosh P.K. Purification and characterization of C-Phycocyanin from cyanobacterial species of marine and freshwater habitat. Protein Expr Purif 40 (2005) 248-255
138. Bhaskar S.U., Gopalaswamy G., and Raghu R. A simple method for efficient extraction and purification of C-phycocyanin from Spirulina platensis Geitler. Indian J Exp Biol 43 (2005) 277-279
139. Houghton J.D., Turner L., and Brown S.B. The effect of gabaculine on tetrapyrrole biosynthesis and heterotrophic growth in Cyanidium caldarium. Biochem J 254 (1988) 907-910
140. Schmidt R.A., Wiebe M.G., and Eriksen N.T. Heterotrophic high cell-density fed-batch cultures of the phycocyanin-producing red alga Galdieria sulphuraria. Biotechnol Bioeng 90 (2005) 77-84
141. Davis S.J., Bhoo S.H., Durski A.M., Walker J.M., and Vierstra R.D. The heme-oxygenase family required for phytochrome chromophore biosynthesis is necessary for proper photomorphogenesis in higher plants. Plant Physiol 126 (2001) 656-669
142. Cornah J.E., Terry M.J., and Smith A.G. Green or red: what stops the traffic in the tetrapyrrole pathway?. Trends Plant Sci 8 (2003) 224-230
143. Walker C.J., and Willows R.D. Mechanism and regulation of Mg-chelatase. Biochem J 327 Pt 2 (1997) 321-333
144. Gora M., Grzybowska E., Rytka J., and Labbe-Bois R. Probing the active-site residues in Saccharomyces cerevisiae ferrochelatase by directed mutagenesis. In vivo and in vitro analyses. J Biol Chem 271 (1996) 11810-11816
145. Zavgorodnyaya A., Papenbrock J., and Grimm B. Yeast 5-aminolevulinate synthase provides additional chlorophyll precursor in transgenic tobacco. Plant J 12 (1997) 169-178
146. Vothknecht U.C., Kannangara C.G., and von Wettstein D. Barley glutamyl tRNAGlu reductase: mutations affecting haem inhibition and enzyme activity. Phytochemistry 47 (1998) 513-519
147. Mukougawa K., Kanamoto H., Kobayashi T., Yokota A., and Kohchi T. Metabolic engineering to produce phytochromes with phytochromobilin, phycocyanobilin, or phycoerythrobilin chromophore in Escherichia coli. FEBS Lett 580 (2006) 1333-1338
148. Kery V., Elleder D., and Kraus J.P. Delta-aminolevulinate increases heme saturation and yield of human cystathionine beta-synthase expressed in Escherichia coli. Arch Biochem Biophys 316 (1995) 24-29
149. Abernethy D.R., Greenblatt D.J., Ameer B., and Shader R.I. Probenecid impairment of acetaminophen and lorazepam clearance: direct inhibition of ether glucuronide formation. J Pharmacol Exp Ther 234 (1985) 345-349
150. Vree T.B., Biggelaar-Martea M., Verwey-van Wissen C.P., and van Ewijk-Beneken Kolmer E.W. Probenecid inhibits the glucuronidation of indomethacin and O-desmethylindomethacin in humans. A pilot experiment. Pharm World Sci 16 (1994) 22-26
151. Turner K.C., and Brouwer K.L. In vitro mechanisms of probenecid-associated alterations in acetaminophen glucuronide hepatic disposition. Drug Metab Dispos 25 (1997) 1017-1021
152. Uchaipichat V., Mackenzie P.I., Guo X.H., Gardner-Stephen D., Galetin A., Houston J.B., et al. Human udp-glucuronosyltransferases: isoform selectivity and kinetics of 4-methylumbelliferone and 1-naphthol glucuronidation, effects of organic solvents, and inhibition by diclofenac and probenecid. Drug Metab Dispos 32 (2004) 413-423
153. Hauser S.C., Ziurys J.C., and Gollan J.L. A membrane transporter mediates access of uridine 5'-diphosphoglucuronic acid from the cytosol into the endoplasmic reticulum of rat hepatocytes: implications for glucuronidation reactions. Biochim Biophys Acta 967 (1988) 149-157
154. Battaglia E., Nowell S., Drake R.R., Mizeracka M., Berg C.L., Magdalou J., et al. Two kinetically-distinct components of UDP-glucuronic acid transport in rat liver endoplasmic reticulum. Biochim Biophys Acta 1283 (1996) 223-231
155. Ozden N, Mukherjee, S. Hyperbilirubinemia, unconjugated. E-Medicine Website; 2004.
156. Cui Y., Konig J., Leier I., Buchholz U., and Keppler D. Hepatic uptake of bilirubin and its conjugates by the human organic anion transporter SLC21A6. J Biol Chem 276 (2001) 9626-9630
157. Campbell S.D., de Morais S.M., and Xu J.J. Inhibition of human organic anion transporting polypeptide OATP 1B1 as a mechanism of drug-induced hyperbilirubinemia. Chem Biol Interact 150 (2004) 179-187
158. Murthy G.D., Byron D., Shoemaker D., Visweswaraiah H., and Pasquale D. The utility of rifampin in diagnosing Gilbert's syndrome. Am J Gastroenterol 96 (2001) 1150-1154
159. Yu H.Y., and Shen Y.Z. Displacement effect of valproate on bilirubin-albumin binding in human plasma. J Formos Med Assoc 98 (1999) 201-204
160. O'Donnell R.W., Johnson D.K., Ziegler L.M., DiMattina A.J., Stone R.I., and Holland J.A. Endothelial NADPH oxidase: mechanism of activation by low-density lipoprotein. Endothelium 10 (2003) 291-297
161. Rueckschloss U., Galle J., Holtz J., Zerkowski H.R., and Morawietz H. Induction of NAD(P)H oxidase by oxidized low-density lipoprotein in human endothelial cells: antioxidative potential of hydroxymethylglutaryl coenzyme A reductase inhibitor therapy. Circulation 104 (2001) 1767-1772
162. Meyer J.W., and Schmitt M.E. A central role for the endothelial NADPH oxidase in atherosclerosis. FEBS Lett 472 (2000) 1-4
163. Howard A.B., Alexander R.W., Nerem R.M., Griendling K.K., and Taylor W.R. Cyclic strain induces an oxidative stress in endothelial cells. Am J Physiol 272 (1997) C421-C427
164. Matsushita H., Lee K.H., and Tsao P.S. Cyclic strain induces reactive oxygen species production via an endothelial NAD(P)H oxidase. J Cell Biochem Suppl. 36 (2001) 99-106
165. Harrison D.G., Cai H., Landmesser U., and Griendling K.K. Interactions of angiotensin II with NAD(P)H oxidase, oxidant stress and cardiovascular disease. J Renin Angiotensin Aldosterone Syst 4 (2003) 51-61
166. Rueckschloss U., Quinn M.T., Holtz J., and Morawietz H. Dose-dependent regulation of NAD(P)H oxidase expression by angiotensin II in human endothelial cells: protective effect of angiotensin II type 1 receptor blockade in patients with coronary artery disease. Arterioscler Thromb Vasc Biol 22 (2002) 1845-1851
167. McCarty M.F. Marinobufagenin may mediate the impact of salty diets on left ventricular hypertrophy by disrupting the protective function of coronary microvascular endothelium. Med Hypotheses 62 (2004) 993-1002
168. Jung O., Schreiber J.G., Geiger H., Pedrazzini T., Busse R., and Brandes R.P. gp91phox-containing NADPH oxidase mediates endothelial dysfunction in renovascular hypertension. Circulation 109 (2004) 1795-1801
169. Morawietz H., Weber M., Rueckschloss U., Lauer N., Hacker A., and Kojda G. Upregulation of vascular NAD(P)H oxidase subunit gp91phox and impairment of the nitric oxide signal transduction pathway in hypertension. Biochem Biophys Res Commun 285 (2001) 1130-1135
170. Zalba G., San Jose G., Moreno M.U., Fortuno M.A., Fortuno A., Beaumont F.J., et al. Oxidative stress in arterial hypertension: role of NAD(P)H oxidase. Hypertension 38 (2001) 1395-1399
171. Inoguchi T., Li P., Umeda F., Yu H.Y., Kakimoto M., Imamura M., et al. High glucose level and free fatty acid stimulate reactive oxygen species production through protein kinase C--dependent activation of NAD(P)H oxidase in cultured vascular cells. Diabetes 49 (2000) 1939-1945
172. Inoguchi T., Sonta T., Tsubouchi H., Etoh T., Kakimoto M., Sonoda N., et al. Protein kinase C-dependent increase in reactive oxygen species (ROS) production in vascular tissues of diabetes: role of vascular NAD(P)H oxidase. J Am Soc Nephrol 14 (2003) S227-S232
173. Kashiwagi A., Shinozaki K., Nishio Y., Maegawa H., Maeno Y., Kanazawa A., et al. Endothelium-specific activation of NAD(P)H oxidase in aortas of exogenously hyperinsulinemic rats. Am J Physiol 277 (1999) E976-E983
174. Katakam P.V., Tulbert C.D., Snipes J.A., Erdos B., Miller A.W., and Busija D.W. Impaired insulin-induced vasodilation in small coronary arteries of Zucker obese rats is mediated by reactive oxygen species. Am J Physiol Heart Circ Physiol 288 (2005) H854-H860
175. Dayal S., Arning E., Bottiglieri T., Boger R.H., Sigmund C.D., Faraci F.M., et al. Cerebral vascular dysfunction mediated by superoxide in hyperhomocysteinemic mice. Stroke 35 (2004) 1957-1962
176. Dong F., Zhang X., Li S.Y., Zhang Z., Ren Q., Culver B., et al. Possible involvement of NADPH oxidase and JNK in homocysteine-induced oxidative stress and apoptosis in human umbilical vein endothelial cells. Cardiovasc Toxicol 5 (2005) 9-20
177. Qamirani E, Ren Y, Kuo L, Hein TW. C-reactive protein inhibits endothelium-dependent NO-mediated dilation in coronary arterioles by activating p38 Kinase and NAD(P)H oxidase. Arterioscler Thromb Vasc Biol 2005.
178. Jaimes E.A., DeMaster E.G., Tian R.X., and Raij L. Stable compounds of cigarette smoke induce endothelial superoxide anion production via NADPH oxidase activation. Arterioscler Thromb Vasc Biol 24 (2004) 1031-1036
179. Fang Q., Sun H., Arrick D.M., and Mayhan W.G. Inhibition of NADPH oxidase improves impaired reactivity of pial arterioles during chronic exposure to nicotine. J Appl Physiol 100 (2006) 631-636
180. Wautier M.P., Chappey O., Corda S., Stern D.M., Schmidt A.M., and Wautier J.L. Activation of NADPH oxidase by AGE links oxidant stress to altered gene expression via RAGE. Am J Physiol Endocrinol Metab 280 (2001) E685-E694
181. Wautier J.L., and Schmidt A.M. Protein glycation: a firm link to endothelial cell dysfunction. Circ Res 95 (2004) 233-238
182. Rupin A., Paysant J., Sansilvestri-Morel P., Lembrez N., Lacoste J.M., Cordi A., et al. Role of NADPH oxidase-mediated superoxide production in the regulation of E-selectin expression by endothelial cells subjected to anoxia/reoxygenation. Cardiovasc Res 63 (2004) 323-330
183. Martin S.F., Chatterjee S., Parinandi N., and Alevriadou B.R. Rac1 inhibition protects against hypoxia/reoxygenation-induced lipid peroxidation in human vascular endothelial cells. Vascul Pharmacol 43 (2005) 148-156
184. Ceran C., Sonmez K., Turkyllmaz Z., Demirogullarl B., Dursun A., Duzgun E., et al. Effect of bilirubin in ischemia/reperfusion injury on rat small intestine. J Pediatr Surg 36 (2001) 1764-1767
185. Hammerman C., Goldschmidt D., Caplan M.S., Kaplan M., Bromiker R., Eidelman A.I., et al. Protective effect of bilirubin in ischemia-reperfusion injury in the rat intestine. J Pediatr Gastroenterol Nutr 35 (2002) 344-349
186. Fondevila C., Katori M., Lassman C., Carmody I., Busuttil R.W., Bach F.H., et al. Biliverdin protects rat livers from ischemia/reperfusion injury. Transplant Proc 35 (2003) 1798-1799
187. Adin C.A., Croker B.P., and Agarwal A. Protective effects of exogenous bilirubin on ischemia-reperfusion injury in the isolated, perfused rat kidney. Am J Physiol Renal Physiol 288 (2005) F778-F784
188. Fondevila C., Shen X.D., Tsuchiyashi S., Yamashita K., Csizmadia E., Lassman C., et al. Biliverdin therapy protects rat livers from ischemia and reperfusion injury. Hepatology 40 (2004) 1333-1341
189. Nakao A., Neto J.S., Kanno S., Stolz D.B., Kimizuka K., Liu F., et al. Protection against ischemia/reperfusion injury in cardiac and renal transplantation with carbon monoxide, biliverdin and both. Am J Transplant 5 (2005) 282-291
190. Li J.M., Gall N.P., Grieve D.J., Chen M., and Shah A.M. Activation of NADPH oxidase during progression of cardiac hypertrophy to failure. Hypertension 40 (2002) 477-484
191. Byrne J.A., Grieve D.J., Bendall J.K., Li J.M., Gove C., Lambeth J.D., et al. Contrasting roles of NADPH oxidase isoforms in pressure-overload versus angiotensin II-induced cardiac hypertrophy. Circ Res 93 (2003) 802-805
192. Wang H.D., Xu S., Johns D.G., Du Y., Quinn M.T., Cayatte A.J., et al. Role of NADPH oxidase in the vascular hypertrophic and oxidative stress response to angiotensin II in mice. Circ Res 88 (2001) 947-953
193. Liu J., Yang F., Yang X.P., Jankowski M., and Pagano P.J. NAD(P)H oxidase mediates angiotensin II-induced vascular macrophage infiltration and medial hypertrophy. Arterioscler Thromb Vasc Biol 23 (2003) 776-782
194. Li J.M., and Shah A.M. ROS generation by nonphagocytic NADPH oxidase: potential relevance in diabetic nephropathy. J Am Soc Nephrol 14 (2003) S221-S226
195. Lee H.B., Yu M.R., Yang Y., Jiang Z., and Ha H. Reactive oxygen species-regulated signaling pathways in diabetic nephropathy. J Am Soc Nephrol 14 (2003) S241-S245
196. Kitada M., Koya D., Sugimoto T., Isono M., Araki S., Kashiwagi A., et al. Translocation of glomerular p47phox and p67phox by protein kinase C-beta activation is required for oxidative stress in diabetic nephropathy. Diabetes 52 (2003) 2603-2614
197. Yoo C.W., Song C.Y., Kim B.C., Hong H.K., and Lee H.S. Glycated albumin induces superoxide generation in mesangial cells. Cell Physiol Biochem 14 (2004) 361-368
198. Chlopicki S., Olszanecki R., Janiszewski M., Laurindo F.R., Panz T., and Miedzobrodzki J. Functional role of NADPH oxidase in activation of platelets. Antioxid Redox Signal 6 (2004) 691-698
199. Herkert O., Diebold I., Brandes R.P., Hess J., Busse R., and Gorlach A. NADPH oxidase mediates tissue factor-dependent surface procoagulant activity by thrombin in human vascular smooth muscle cells. Circulation 105 (2002) 2030-2036
200. Herkert O., Djordjevic T., BelAiba R.S., and Gorlach A. Insights into the redox control of blood coagulation: role of vascular NADPH oxidase-derived reactive oxygen species in the thrombogenic cycle. Antioxid Redox Signal 6 (2004) 765-776
201. Caramori G., and Papi A. Oxidants and asthma. Thorax 59 (2004) 170-173
202. Yoshimaru T., Suzuki Y., Matsui T., Yamashita K., Ochiai T., Yamaki M., et al. Blockade of superoxide generation prevents high-affinity immunoglobulin E receptor-mediated release of allergic mediators by rat mast cell line and human basophils. Clin Exp Allergy 32 (2002) 612-618
203. Suzuki Y., Yoshimaru T., Matsui T., Inoue T., Niide O., Nunomura S., et al. Fc epsilon RI signaling of mast cells activates intracellular production of hydrogen peroxide: role in the regulation of calcium signals. J Immunol 171 (2003) 6119-6127
204. Ohrui T., Yasuda H., Yamaya M., Matsui T., and Sasaki H. Transient relief of asthma symptoms during jaundice: a possible beneficial role of bilirubin. Tohoku J Exp Med 199 (2003) 193-196
205. Takamiya R., Murakami M., Kajimura M., Goda N., Makino N., Takamiya Y., et al. Stabilization of mast cells by heme oxygenase-1: an anti-inflammatory role. Am J Physiol Heart Circ Physiol 283 (2002) H861-H870
206. Lo Y.Y., Conquer J.A., Grinstein S., and Cruz T.F. Interleukin-1 beta induction of c-fos and collagenase expression in articular chondrocytes: involvement of reactive oxygen species. J Cell Biochem 69 (1998) 19-29
207. Lo Y.Y., Wong J.M., and Cruz T.F. Reactive oxygen species mediate cytokine activation of c-Jun NH2-terminal kinases. J Biol Chem 271 (1996) 15703-15707
208. Mendes A.F., Caramona M.M., Carvalho A.P., and Lopes M.C. Differential roles of hydrogen peroxide and superoxide in mediating IL-1-induced NF-kappa B activation and iNOS expression in bovine articular chondrocytes. J Cell Biochem 88 (2003) 783-793
209. Jouzeau J.Y., Pacquelet S., Boileau C., Nedelec E., Presle N., Netter P., et al. Nitric oxide (NO) and cartilage metabolism: NO effects are modulated by superoxide in response to IL-1. Biorheology 39 (2002) 201-214
210. Oh M., Fukuda K., Asada S., Yasuda Y., and Tanaka S. Concurrent generation of nitric oxide and superoxide inhibits proteoglycan synthesis in bovine articular chondrocytes: involvement of peroxynitrite. J Rheumatol 25 (1998) 2169-2174
211. Vozenin-Brotons M.C., Sivan V., Gault N., Renard C., Geffrotin C., Delanian S., et al. Antifibrotic action of Cu/Zn SOD is mediated by TGF-beta1 repression and phenotypic reversion of myofibroblasts. Free Radic Biol Med 30 (2001) 30-42
212. Liu R.M., Liu Y., Forman H.J., Olman M., and Tarpey M.M. Glutathione regulates transforming growth factor-beta-stimulated collagen production in fibroblasts. Am J Physiol Lung Cell Mol Physiol 286 (2004) L121-L128
213. Bataller R., Schwabe R.F., Choi Y.H., Yang L., Paik Y.H., Lindquist J., et al. NADPH oxidase signal transduces angiotensin II in hepatic stellate cells and is critical in hepatic fibrosis. J Clin Invest 112 (2003) 1383-1394
214. 2-generating NADH oxidase in human lung fibroblasts by transforming growth factor beta 1. J Biol Chem 270 (1995) 30334-30338
215. Sharma K., Cook A., Smith M., Valancius C., and Inscho E.W. TGF-beta impairs renal autoregulation via generation of ROS. Am J Physiol Renal Physiol 288 (2005) F1069-F1077
216. Wang H.D., Yamaya M., Okinaga S., Jia Y.X., Kamanaka M., Takahashi H., et al. Bilirubin ameliorates bleomycin-induced pulmonary fibrosis in rats. Am J Respir Crit Care Med 165 (2002) 406-411
217. Morse D. The role of heme oxygenase-1 in pulmonary fibrosis. Am J Respir Cell Mol Biol 29 (2003) S82-S86
218. Tsuburai T., Suzuki M., Nagashima Y., Suzuki S., Inoue S., Hasiba T., et al. Adenovirus-mediated transfer and overexpression of heme oxygenase 1 cDNA in lung prevents bleomycin-induced pulmonary fibrosis via a Fas-Fas ligand-independent pathway. Hum Gene Ther 13 (2002) 1945-1960
219. Ohrui T., Higuchi M., Kanda A., Matsui T., Sato E., and Sasaki H. A patient with exacerbation of idiopathic pulmonary fibrosis which was resolved probably due to the coexisting hyperbilirubinemia?. Tohoku J Exp Med 193 (2001) 245-249
220. Sambo P., Baroni S.S., Luchetti M., Paroncini P., Dusi S., Orlandini G., et al. Oxidative stress in scleroderma: maintenance of scleroderma fibroblast phenotype by the constitutive up-regulation of reactive oxygen species generation through the NADPH oxidase complex pathway. Arthritis Rheum 44 (2001) 2653-2664
221. Lavigne M.C., and Eppihimer M.J. Cigarette smoke condensate induces MMP-12 gene expression in airway-like epithelia. Biochem Biophys Res Commun 330 (2005) 194-203
222. Darden A.G., Ries W.L., Wolf W.C., Rodriguiz R.M., and Key Jr. L.L. Osteoclastic superoxide production and bone resorption: stimulation and inhibition by modulators of NADPH oxidase. J Bone Miner Res 11 (1996) 671-675
223. Yang S., Zhang Y., Ries W., and Key L. Expression of Nox4 in osteoclasts. J Cell Biochem 92 (2004) 238-248
224. Steinbeck M.J., Kim J.K., Trudeau M.J., Hauschka P.V., and Karnovsky M.J. Involvement of hydrogen peroxide in the differentiation of clonal HD-11EM cells into osteoclast-like cells. J Cell Physiol 176 (1998) 574-587
225. Bax B.E., Alam A.S., Banerji B., Bax C.M., Bevis P.J., Stevens C.R., et al. Stimulation of osteoclastic bone resorption by hydrogen peroxide. Biochem Biophys Res Commun 183 (1992) 1153-1158
226. Fraser J.H., Helfrich M.H., Wallace H.M., and Ralston S.H. Hydrogen peroxide, but not superoxide, stimulates bone resorption in mouse calvariae. Bone 19 (1996) 223-226
227. Yang S., Ries W.L., and Key Jr. L.L. Superoxide generation in transformed B-lymphocytes from patients with severe, malignant osteopetrosis. Mol Cell Biochem 199 (1999) 15-24
228. Lean J.M., Davies J.T., Fuller K., Jagger C.J., Kirstein B., Partington G.A., et al. A crucial role for thiol antioxidants in estrogen-deficiency bone loss. J Clin Invest 112 (2003) 915-923
229. Lean J.M., Jagger C.J., Kirstein B., Fuller K., and Chambers T.J. Hydrogen peroxide is essential for estrogen-deficiency bone loss and osteoclast formation. Endocrinology 146 (2005) 728-735
230. Razzouk S., Lieberherr M., and Cournot G. Rac-GTPase, osteoclast cytoskeleton and bone resorption. Eur J Cell Biol 78 (1999) 249-255
231. Chan K.A., Andrade S.E., Boles M., Buist D.S., Chase G.A., Donahue J.G., et al. Inhibitors of hydroxymethylglutaryl-coenzyme A reductase and risk of fracture among older women. Lancet 355 (2000) 2185-2188
232. Solomon D.H., Finkelstein J.S., Wang P.S., and Avorn J. Statin lipid-lowering drugs and bone mineral density. Pharmacoepidemiol Drug Saf 14 (2005) 219-226
233. Kuzuya M., Suzuki Y., Asai T., Koike T., Kanda S., Nakamura A., et al. Atorvastatin, 3-hydroxy-3-methylglutaryl coenzyme a reductase inhibitor, reduces bone resorption in the elderly. J Am Geriatr Soc 51 (2003) 1677-1678
234. Grasser W.A., Baumann A.P., Petras S.F., Harwood Jr. H.J., Devalaraja R., Renkiewicz R., et al. Regulation of osteoclast differentiation by statins. J Musculoskelet Neuronal Interact 3 (2003) 53-62
235. van beek E., Lowik C., van der P.G., and Papapoulos S. The role of geranylgeranylation in bone resorption and its suppression by bisphosphonates in fetal bone explants in vitro: A clue to the mechanism of action of nitrogen-containing bisphosphonates. J Bone Miner Res 14 (1999) 722-729
236. Reszka A.A., and Rodan G.A. Mechanism of action of bisphosphonates. Curr Osteoporos Rep 1 (2003) 45-52
237. Irani K., and Goldschmidt-Clermont P.J. Ras, superoxide and signal transduction. Biochem Pharmacol 55 (1998) 1339-1346
238. Suh Y.A., Arnold R.S., Lassegue B., Shi J., Xu X., Sorescu D., et al. Cell transformation by the superoxide-generating oxidase Mox1. Nature 401 (1999) 79-82
239. Arnold R.S., Shi J., Murad E., Whalen A.M., Sun C.Q., Polavarapu R., et al. Hydrogen peroxide mediates the cell growth and transformation caused by the mitogenic oxidase Nox1. Proc Natl Acad Sci U.S.A 98 (2001) 5550-5555
240. Brar S.S., Kennedy T.P., Sturrock A.B., Huecksteadt T.P., Quinn M.T., Whorton A.R., et al. An NAD(P)H oxidase regulates growth and transcription in melanoma cells. Am J Physiol Cell Physiol 282 (2002) C1212-C1224
241. Brar S.S., Corbin Z., Kennedy T.P., Hemendinger R., Thornton L., Bommarius B., et al. NOX5 NAD(P)H oxidase regulates growth and apoptosis in DU 145 prostate cancer cells. Am J Physiol Cell Physiol 285 (2003) C353-C369
242. Brar S.S., Kennedy T.P., Quinn M., and Hoidal J.R. Redox signaling of NF-kappaB by membrane NAD(P)H oxidases in normal and malignant cells. Protoplasma 221 (2003) 117-127
243. Mitsushita J., Lambeth J.D., and Kamata T. The superoxide-generating oxidase Nox1 is functionally required for Ras oncogene transformation. Cancer Res 64 (2004) 3580-3585
244. Vaquero E.C., Edderkaoui M., Pandol S.J., Gukovsky I., and Gukovskaya A.S. Reactive oxygen species produced by NAD(P)H oxidase inhibit apoptosis in pancreatic cancer cells. J Biol Chem 279 (2004) 34643-34654
245. Dong J.M., Zhao S.G., Huang G.Y., and Liu Q. NADPH oxidase-mediated generation of reactive oxygen species is critically required for survival of undifferentiated human promyelocytic leukemia cell line HL-60. Free Radic Res 38 (2004) 629-637
246. Lim S.D., Sun C., Lambeth J.D., Marshall F., Amin M., Chung L., et al. Increased Nox1 and hydrogen peroxide in prostate cancer. Prostate 62 (2005) 200-207
247. Abid M.R., Kachra Z., Spokes K.C., and Aird W.C. NADPH oxidase activity is required for endothelial cell proliferation and migration. FEBS Lett 486 (2000) 252-256
248. Ushio-Fukai M., and Alexander R.W. Reactive oxygen species as mediators of angiogenesis signaling: role of NAD(P)H oxidase. Mol Cell Biochem 264 (2004) 85-97
249. Kim H.W., Murakami A., Williams M.V., and Ohigashi H. Mutagenicity of reactive oxygen and nitrogen species as detected by co-culture of activated inflammatory leukocytes and AS52 cells. Carcinogenesis 24 (2003) 235-241
250. Ohshima H., Tatemichi M., and Sawa T. Chemical basis of inflammation-induced carcinogenesis. Arch Biochem Biophys 417 (2003) 3-11
251. Teufelhofer O., Parzefall W., Kainzbauer E., Ferk F., Freiler C., Knasmuller S., et al. Superoxide generation from Kupffer cells contributes to hepatocarcinogenesis: studies on NADPH oxidase knockout mice. Carcinogenesis 26 (2005) 319-329
252. Shimohama S., Tanino H., Kawakami N., Okamura N., Kodama H., Yamaguchi T., et al. Activation of NADPH oxidase in Alzheimer's disease brains. Biochem Biophys Res Commun 273 (2000) 5-9
253. Zekry D., Epperson T.K., and Krause K.H. A role for NOX NADPH oxidases in Alzheimer's disease and other types of dementia?. IUBMB Life 55 (2003) 307-313
254. Jana A., and Pahan K. Fibrillar amyloid-beta peptides kill human primary neurons via NADPH oxidase-mediated activation of neutral sphingomyelinase. Implications for Alzheimer's disease. J Biol Chem 279 (2004) 51451-51459
255. Gao H.M., Jiang J., Wilson B., Zhang W., Hong J.S., and Liu B. Microglial activation-mediated delayed and progressive degeneration of rat nigral dopaminergic neurons: relevance to Parkinson's disease. J Neurochem 81 (2002) 1285-1297
256. Gao H.M., Liu B., and Hong J.S. Critical role for microglial NADPH oxidase in rotenone-induced degeneration of dopaminergic neurons. J Neurosci 23 (2003) 6181-6187
257. Furukawa S., Fujita T., Shimabukuro M., Iwaki M., Yamada Y., Nakajima Y., et al. Increased oxidative stress in obesity and its impact on metabolic syndrome. J Clin Invest 114 (2004) 1752-1761
258. Mahadev K., Wu X., Zilbering A., Zhu L., Lawrence J.T., and Goldstein B.J. Hydrogen peroxide generated during cellular insulin stimulation is integral to activation of the distal insulin signaling cascade in 3T3-L1 adipocytes. J Biol Chem 276 (2001) 48662-48669
259. Goldstein B.J., Mahadev K., and Wu X. Redox paradox: insulin action is facilitated by insulin-stimulated reactive oxygen species with multiple potential signaling targets. Diabetes 54 (2005) 311-321
260. Imparl-Radosevich J., Deas S., Polansky M.M., Baedke D.A., Ingebritsen T.S., Anderson R.A., et al. Regulation of PTP-1 and insulin receptor kinase by fractions from cinnamon: implications for cinnamon regulation of insulin signalling. Horm Res 50 (1998) 177-182
261. Khan A., Safdar M., Ali Khan M.M., Khattak K.N., and Anderson R.A. Cinnamon improves glucose and lipids of people with type 2 diabetes. Diabetes Care 26 (2003) 3215-3218
262. Mander P., and Brown G.C. Activation of microglial NADPH oxidase is synergistic with glial iNOS expression in inducing neuronal death: a dual-key mechanism of inflammatory neurodegeneration. J Neuroinflammation 2 (2005) 20
263. Nikolova S., Lee Y.S., Lee Y.S., and Kim J.A. Rac1-NADPH oxidase-regulated generation of reactive oxygen species mediates glutamate-induced apoptosis in SH-SY5Y human neuroblastoma cells. Free Radic Res 39 (2005) 1295-1304
264. Sonkusare S.K., Kaul C.L., and Ramarao P. Dementia of Alzheimer's disease and other neurodegenerative disorders--memantine, a new hope. Pharmacol Res 51 (2005) 1-17
265. Salinska E., Danysz W., and Lazarewicz J.W. The role of excitotoxicity in neurodegeneration. Folia Neuropathol 43 (2005) 322-339
266. Xie Z., Wei M., Morgan T.E., Fabrizio P., Han D., Finch C.E., et al. Peroxynitrite mediates neurotoxicity of amyloid beta-peptide1-42- and lipopolysaccharide-activated microglia. J Neurosci 22 (2002) 3484-3492
267. Tieu K., Ischiropoulos H., and Przedborski S. Nitric oxide and reactive oxygen species in Parkinson's disease. IUBMB Life 55 (2003) 329-335
268. Chung J.M. The Role of Reactive Oxygen Species (ROS) in Persistent Pain. Mol Interv 4 (2004) 248-250
269. Kim H.K., Park S.K., Zhou J.L., Taglialatela G., Chung K., Coggeshall R.E., et al. Reactive oxygen species (ROS) play an important role in a rat model of neuropathic pain. Pain 111 (2004) 116-124
270. Muscoli C., Mollace V., Wheatley J., Masini E., Ndengele M., Wang Z.Q., et al. Superoxide-mediated nitration of spinal manganese superoxide dismutase: a novel pathway in N-methyl-D-aspartate-mediated hyperalgesia. Pain 111 (2004) 96-103
271. Wang Z.Q., Porreca F., Cuzzocrea S., Galen K., Lightfoot R., Masini E., et al. A newly identified role for superoxide in inflammatory pain. J Pharmacol Exp Ther 309 (2004) 869-878
272. Kishida K.T., Pao M., Holland S.M., and Klann E. NADPH oxidase is required for NMDA receptor-dependent activation of ERK in hippocampal area CA1. J Neurochem 94 (2005) 299-306
273. Serrano F., Kolluri N.S., Wientjes F.B., Card J.P., and Klann E. NADPH oxidase immunoreactivity in the mouse brain. Brain Res 988 (2003) 193-198
274. Zhang X., Huang J., and McNaughton P.A. NGF rapidly increases membrane expression of TRPV1 heat-gated ion channels. EMBO J 24 (2005) 4211-4223
275. Ji R.R., Samad T.A., Jin S.X., Schmoll R., and Woolf C.J. p38 MAPK activation by NGF in primary sensory neurons after inflammation increases TRPV1 levels and maintains heat hyperalgesia. Neuron 36 (2002) 57-68
276. Cortright D.N., and Szallasi A. Biochemical pharmacology of the vanilloid receptor TRPV1. An update. Eur J Biochem 271 (2004) 1814-1819
277. Jin X., Morsy N., Winston J., Pasricha P.J., Garrett K., and Akbarali H.I. Modulation of TRPV1 by nonreceptor tyrosine kinase, c-Src kinase. Am J Physiol Cell Physiol 287 (2004) C558-C563
278. Jain N.K., Patil C.S., Singh A., and Kulkarni S.K. Sildenafil, a phosphodiesterase-5 inhibitor, enhances the antinociceptive effect of morphine. Pharmacology 67 (2003) 150-156
279. Kim H., Sasaki T., Maeda K., Koya D., Kashiwagi A., and Yasuda H. Protein kinase Cbeta selective inhibitor LY333531 attenuates diabetic hyperalgesia through ameliorating cGMP level of dorsal root ganglion neurons. Diabetes 52 (2003) 2102-2109
280. Beak S.M., Lee Y.S., and Kim J.A. NADPH oxidase and cyclooxygenase mediate the ultraviolet B-induced generation of reactive oxygen species and activation of nuclear factor-kappaB in HaCaT human keratinocytes. Biochimie 86 (2004) 425-429
281. Wang H., and Kochevar I.E. Involvement of UVB-induced reactive oxygen species in TGF-beta biosynthesis and activation in keratinocytes. Free Radic Biol Med 38 (2005) 890-897
282. Zhou J., Struthers A.D., and Lyles G.A. Differential effects of some cell signalling inhibitors upon nitric oxide synthase expression and nuclear factor-kappaB activation induced by lipopolysaccharide in rat aortic smooth muscle cells. Pharmacol Res 39 (1999) 363-373
283. Pawate S., Shen Q., Fan F., and Bhat N.R. Redox regulation of glial inflammatory response to lipopolysaccharide and interferongamma. J Neurosci Res 77 (2004) 540-551
284. Otterbein L., Chin B.Y., Otterbein S.L., Lowe V.C., Fessler H.E., and Choi A.M. Mechanism of hemoglobin-induced protection against endotoxemia in rats: a ferritin-independent pathway. Am J Physiol 272 (1997) L268-L275
285. Wang W.W., Smith D.L., and Zucker S.D. Bilirubin inhibits iNOS expression and NO production in response to endotoxin in rats. Hepatology 40 (2004) 424-433
286. Kadl A., Pontiller J., Leitinger N., Ruecker F., Exner M., and Wagner O. Bilirubin improves the clinical outcome in a mouse model of endotoxemia. FASEB J 19 (2005) 685
287. Fantone J.C., and Ward P.A. Polymorphonuclear leukocyte-mediated cell and tissue injury: oxygen metabolites and their relations to human disease. Hum Pathol 16 (1985) 973-978
288. Babior B.M. Phagocytes and oxidative stress. Am J Med 109 (2000) 33-44
289. Vaananen P.M., Meddings J.B., and Wallace J.L. Role of oxygen-derived free radicals in indomethacin-induced gastric injury. Am J Physiol 261 (1991) G470-G475
290. Arai T., Yoshikai Y., Kamiya J., Nagino M., Uesaka K., Yuasa N., et al. Bilirubin impairs bactericidal activity of neutrophils through an antioxidant mechanism in vitro. J Surg Res 96 (2001) 107-113
291. Maemura K., Zheng Q., Wada T., Ozaki M., Takao S., Aikou T., et al. Reactive oxygen species are essential mediators in antigen presentation by Kupffer cells. Immunol Cell Biol 83 (2005) 336-343
292. Wu J., Ma J., Fan S.T., Schlitt H.J., and Tsui T.Y. Bilirubin derived from heme degradation suppresses MHC class II expression in endothelial cells. Biochem Biophys Res Commun 338 (2005) 890-896
293. Kimura T., Kameoka M., and Ikuta K. Amplification of superoxide anion generation in phagocytic cells by HIV-1 infection. FEBS Lett 326 (1993) 232-236
294. Bautista A.P. Chronic alcohol intoxication attenuates human immunodeficiency virus-1 glycoprotein 120-induced superoxide anion release by isolated Kupffer cells. Alcohol Clin Exp Res 22 (1998) 474-480
295. Gu Y., Wu R.F., Xu Y.C., Flores S.C., and Terada L.S. HIV Tat activates c-Jun amino-terminal kinase through an oxidant-dependent mechanism. Virology 286 (2001) 62-71
296. Vilhardt F., Plastre O., Sawada M., Suzuki K., Wiznerowicz M., Kiyokawa E., et al. The HIV-1 Nef protein and phagocyte NADPH oxidase activation. J Biol Chem 277 (2002) 42136-42143
297. Wu R.F., Gu Y., Xu Y.C., Mitola S., Bussolino F., and Terada L.S. Human immunodeficiency virus type 1 Tat regulates endothelial cell actin cytoskeletal dynamics through PAK1 activation and oxidant production. J Virol 78 (2004) 779-789
298. Jana A., and Pahan K. Human immunodeficiency virus type 1 gp120 induces apoptosis in human primary neurons through redox-regulated activation of neutral sphingomyelinase. J Neurosci 24 (2004) 9531-9540
299. Olivetta E., Pietraforte D., Schiavoni I., Minetti M., Federico M., and Sanchez M. HIV-1 Nef regulates the release of superoxide anions from human macrophages. Biochem.J 390 (2005) 591-602
300. Storz P., Doppler H., and Toker A. Protein kinase Cdelta selectively regulates protein kinase D-dependent activation of NF-kappaB in oxidative stress signaling. Mol Cell Biol 24 (2004) 2614-2626
301. Storz P., Doppler H., and Toker A. Activation loop phosphorylation controls protein kinase D-dependent activation of nuclear factor kappaB. Mol Pharmacol 66 (2004) 870-879
302. Nabel G., and Baltimore D. An inducible transcription factor activates expression of human immunodeficiency virus in T cells. Nature 326 (1987) 711-713
303. Palmieri C., Trimboli F., Puca A., Fiume G., Scala G., and Quinto I. Inhibition of HIV-1 replication in primary human monocytes by the IkappaB-alphaS32/36A repressor of NF-kappaB. Retrovirology 1 (2004) 45
304. Baba M. Recent status of HIV-1 gene expression inhibitors. Antiviral Res (2006)
305. Devadas K., and Dhawan S. Hemin Activation Ameliorates HIV-1 Infection via Heme Oxygenase-1 Induction. J Immunol 176 (2006) 4252-4257
306. McPhee F., Caldera P.S., Bemis G.W., McDonagh A.F., Kuntz I.D., and Craik C.S. Bile pigments as HIV-1 protease inhibitors and their effects on HIV-1 viral maturation and infectivity in vitro. Biochem J 320 (1996) 681-686
307. Borgmann K., Gendelman H.E., and Ghorpade A. Isolation and HIV-1 infection of primary human microglia from fetal and adult tissue. Methods Mol Biol 304 (2005) 49-70
308. Ambasta R.K., Kumar P., Griendling K.K., Schmidt H.H., Busse R., and Brandes R.P. Direct interaction of the novel Nox proteins with p22phox is required for the formation of a functionally active NADPH oxidase. J Biol Chem 279 (2004) 45935-45941
309. Clark R.A., Epperson T.K., and Valente A.J. Mechanisms of activation of NADPH oxidases. Jpn.J Infect Dis 57 (2004) S22-S23
310. Krause K.H. Tissue distribution and putative physiological function of NOX family NADPH oxidases. Jpn J Infect Dis 57 (2004) S28-S29
311. Takeya R., and Sumimoto H. Molecular mechanism for activation of superoxide-producing NADPH oxidases. Mol Cells 16 (2003) 271-277