NADPH oxidase: Recent evidence for its role in erectile dysfunction

Asian Journal of Andrology

Volumn 10, Issue 1, 2008, Pages 6-13

  Jin, Liming ^a,b   Burnett, Arthur L ^a  

^a DEPARTMENT OF PATHOLOGY   (United States)

^b UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

Erectile function; Nitric oxide; Penis; Reactive oxygen species; Superoxide

Indexed keywords

HOMOCYSTEINE; OXIDOREDUCTASE; PHOSPHODIESTERASE V INHIBITOR; PROTEIN KINASE C; REACTIVE OXYGEN METABOLITE; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE PHOSPHATE OXIDASE; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE PHOSPHATE OXIDASE 2; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE PHOSPHATE OXIDASE 3; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE PHOSPHATE OXIDASE 4; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE PHOSPHATE OXIDASE 5; SILDENAFIL; SUPEROXIDE DISMUTASE; TACROLIMUS; THIOBARBITURIC ACID REACTIVE SUBSTANCE; UNCLASSIFIED DRUG;

AGING; CELLULAR DISTRIBUTION; ENDOTHELIUM CELL; ENZYME ACTIVATION; ENZYME ACTIVITY; ENZYME INHIBITION; ENZYME LOCALIZATION; ERECTILE DYSFUNCTION; FIBROBLAST; HUMAN; HYPERCHOLESTEROLEMIA; HYPERHOMOCYSTEINEMIA; HYPERLIPIDEMIA; HYPERTENSION; NERVE INJURY; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; PATHOGENESIS; PREVALENCE; PROTEIN EXPRESSION; REVIEW; RISK FACTOR; SMOOTH MUSCLE FIBER;

AGING; ANIMALS; DIABETES MELLITUS; ERECTILE DYSFUNCTION; HUMANS; HYPERHOMOCYSTEINEMIA; HYPERLIPIDEMIAS; HYPERTENSION; MALE; NADPH OXIDASE; REACTIVE OXYGEN SPECIES;

EID: 37749021430     PISSN: 1008682X     EISSN: 17457262     Source Type: Journal    
DOI: 10.1111/j.1745-7262.2008.00371.x     Document Type: Review

References (82)

1. Aytac IA, Mckinlay JB, Krane RJ. The likely worldwide increase in erectile dysfunction between 1995 and 2025 and some possible policy consequences. BJU Int 1999; 84: 50-6.
2. Jensen J, Lendorf A, Stimpel H, Frost J, Ibsen H, Rosenkilde P. The prevalence and etiology of impotence in 101 male hypertensive outpatients. Am J Hypertens 1999; 12: 271-5.
3. Kaiser FE, Viosca SP, Morley JE, Mooradian AD, Davis SS, Korenman SG. Impotence and aging: Clinical and hormonal factors. J Am Geriatr Soc 1988; 36: 511-9.
4. Keegan A, Cotter MA, Cameron NE. Effects of diabetes and treatment with the antioxidant alpha-lipoic acid on endothelial and neurogenic responses of corpus cavernosum in rats. Diabetologia 1999; 42: 343-50.
5. Kim SC, Kim IK, Seo KK, Baek KJ, Lee MY. Involvement of superoxide radical in the impaired endothelium-dependent relaxation of cavernous smooth muscle in hypercholesterolemic rabbits. Urol Res 1997; 25: 341-6.
6. Ushiyama M, Morita T, Kuramochi T, Yagi S, Katayama S. Erectile dysfunction in hypertensive rats results from impairment of the relaxation evoked by neurogenic carbon monoxide and nitric oxide. Hypertens Res 2004; 27: 253-61.
7. Burnett AL, Musicki B, Jin L, Bivalacqua TJ. Nitric oxide/redox-based signalling as a therapeutic target for penile disorders. Expert Opin Ther Targets 2006; 10: 445-57.
8. Dobrina A, Patriarca P. Neutrophil-endothelial cell interaction. Evidence for and mechanisms of the self-protection of bovine microvascular endothelial cells from hydrogen peroxide-induced oxidative stress. J Clin Invest 1986; 78: 462-71.
9. Lagoda G, Jin L, Lehrfeld TJ, Liu T, Burnett AL. Fk506 and sildenafil promote erectile function recovery after cavernous nerve injury through antioxidative mechanisms. J Sex Med 2007; 4: 908-16.
10. Rosen RC, Fisher WA, Eardley I, Niederberger C, Nadel A, Sand M. The multinational men's attitudes to life events and sexuality (males) study: I. Prevalence of erectile dysfunction and related health concerns in the general population. Curr Med Res Opin 2004; 20: 607-17.
11. Behr-Roussel D, Chamiot-Clerc P, Bernabe J, Mevel K, Alexandre L, Safar ME, et al. Erectile dysfunction in spontaneously hypertensive rats: pathophysiological mechanisms. Am J Physiol Regul Integr Comp Physiol 2003; 284: R682-8.
12. Chitaley K, Webb RC, Dorrance AM, Mills TM. Decreased penile erection in doca-salt and stroke prone-spontaneously hypertensive rats. Int J Impot Res 2001; 13 (Suppl 5): S16-20.
13. Moore CR, Wang R. Pathophysiology and treatment of diabetic erectile dysfunction. Asian J Androl 2006; 8: 675-84.
14. Morano S, Gatti A, Mandosi E, Tiberti C, Fallarino M, Cipriani R, et al. Circulating monocyte oxidative activity is increased in patients with type 2 diabetes and erectile dysfunction. J Urol 2007; 177: 655-9.
15. Ryu JK, Kim DJ, Lee T, Kang YS, Yoon SM, Suh JK. The role of free radical in the pathogenesis of impotence in streptozotocin-induced diabetic rats. Yonsei Med J 2003; 44: 236-41.
16. Rasmussen H, Takuwa Y, Park S. Protein kinase C in the regulation of smooth muscle contraction. FASEB J 1987; 1: 177-85.
17. Ganz MB, Seftel A. Glucose-induced changes in protein kinase C and nitric oxide are prevented by vitamin E. Am J Physiol Endocrinol Metab 2000; 278: E146-52.
18. Bivalacqua TJ, Usta MF, Kendirci M, Pradhan L, Alvarez X, Champion HC, et al. Superoxide anion production in the rat penis impairs erectile function in diabetes: Influence of in vivo extracellular superoxide dismutase gene therapy. J Sex Med 2005; 2: 187-97; discussion 97-8.
19. Ahn TY, Gomez-Coronado D, Martinez V, Cuevas P, Goldstein I, Saenz de Tejada I. Enhanced contractility of rabbit corpus cavernosum smooth muscle by oxidized low density lipoproteins. Int J Impot Res 1999; 11: 9-14.
20. Kim SC. Hyperlipidemia and erectile dysfunction. Asian J Androl 2000; 2: 161-6.
21. Jin L, Caldwell RB, Li-Masters T, Caldwell RW. Homocysteine induces endothelial dysfunction via inhibition of arginine transport. J Physiol Pharmacol 2007; 58: 191-206.
22. Handy DE, Zhang Y, Loscalzo J. Homocysteine down-regulates cellular glutathione peroxidase (gpx1) by decreasing translation. J Biol Chem 2005; 280: 15518-25.
23. Becker JS, Adler A, Schneeberger A, Huang H, Wang Z, Walsh E, et al. Hyperhomocysteinemia, a cardiac metabolic disease: Role of nitric oxide and the p22phox subunit of NADPH oxidase. Circulation 2005; 111: 2112-8.
24. Khan MA, Thompson CS, Emsley AM, Mumtaz FH, Mikhailidis DP, Angelini GD, et al. The interaction of homocysteine and copper markedly inhibits the relaxation of rabbit corpus cavernosum: New risk factors for angiopathic erectile dysfunction? BJU Int 1999; 84: 720-4.
25. Koupparis AJ, Jeremy J, Angelini G, Persad RAJ, Shukla N. Penicillamine administration reverses the inhibitory effect of hyperhomocysteinaemia on endothelium-dependent relaxation in the corpus cavernosum in the rabbit. BJU Int 2006; 98: 440-4.
26. Selvin E, Burnett AL, Platz EA. Prevalence and risk factors for erectile dysfunction in the US. Am J Med 2007; 120: 151-7.
27. Bivalacqua TJ, Armstrong JS, Biggerstaff J, Abdel-Mageed AB, Kadowitz PJ, Hellstrom WJ, et al. Gene transfer of extracellular sod to the penis reduces superoxide and improves erectile function in aged rats. Am J Physiol Heart Circ Physiol 2003; 284: H1408-21.
28. Ferrini MG, Davila HH, Valente EGA, Gonzalez-Cadavid NF, Rajfer J. Aging-related induction of inducible nitric oxide syn-thase is vasculo-protective to the arterial media. Cardiovasc Res 2004; 61: 796-805.
29. Ozkara H, Alan C, Atukeren P, Uyaner I, Demirci C, Gumustas MK, et al. Changes of nitric oxide synthase-containing nerve fibers and parameters for oxidative stress after unilateral cavernous nerve resection or manuplation in rat penis. Chin J Physiol 2006; 49: 160-6.
30. Bellavite P. The superoxide-forming enzymatic system of phagocytes. Free Radic Biol Med 1988; 4: 225-61.
31. Leto TL, Lomax KJ, Volpp BD, Nunoi H, Sechler JM, Nauseef WM, et al. Cloning of a 67-kd neutrophil oxidase factor with similarity to a noncatalytic region of p60c-src. Science 1990; 248: 727-30.
32. Parkos CA, Allen RA, Cochrane CG, Jesaitis AJ. The quaternary structure of the plasma membrane b-type cytochrome of human granulocytes. Biochim Biophys Acta 1988; 932: 71-83.
33. Park JW, Ma M, Ruedi JM, Smith RM, Babior BM. The cytosolic components of the respiratory burst oxidase exist as a m(r) approximately 240,000 complex that acquires a membrane-binding site during activation of the oxidase in a cell-free system. J Biol Chem 1992; 267: 17327-32.
34. Catarzi S, Biagioni C, Giannoni E, Favilli F, Marcucci T, Iantomasi T, et al. Redox regulation of platelet-derived-growth-factor-receptor: Role of NADPH-oxidase and c-src tyrosine kinase. Biochim Biophys Acta 2005; 1745: 166-75.
35. Picchi A, Gao X, Belmadani S, Potter BJ, Focardi M, Chilian WM, et al. Tumor necrosis factor-{alpha} induces endothelial dysfunction in the prediabetic metabolic syndrome. Circ Res 2006; 99: 69-77.
36. Laplante MA, de Champlain J. The interrelation of the angio-tensin and endothelin systems on the modulation of NAD(P)H oxidase. Can J Physiol Pharmacol 2006; 84: 21-8.
37. Vendrov AE, Madamanchi NR, Hakim ZS, Rojas M, Runge MS. Thrombin and NAD(P)H oxidase-mediated regulation of cd44 and bmp4-id pathway in vsmc, restenosis, and atherosclerosis. Circ Res 2006; 98: 1254-63.
38. Peshavariya HM, Dusting GJ, Selemidis S. Analysis of dihydro-ethidium fluorescence for the detection of intracellular and extracellular superoxide produced by NADPH oxidase. Free Radic Res 2007; 41: 699-712.
39. Suzuma I, Murakami T, Suzuma K, Kaneto H, Watanabe D, Ojima T, et al. Cyclic stretch-induced reactive oxygen species generation enhances apoptosis in retinal pericytes through c-jun NH2-terminal kinase activation. Hypertension 2007; 49: 347-54.
40. Hong NJ, Garvin JL. Flow increases superoxide production by NADPH oxidase via activation of Na-K-2Cl cotransport and mechanical stress in thick ascending limbs. Am J Physiol Renal Physiol 2007; 292: F993-8.
41. Rotrosen D, Leto TL. Phosphorylation of neutrophil 47-kda cytosolic oxidase factor. Translocation to membrane is associated with distinct phosphorylation events. J Biol Chem 1990; 265: 19910-5.
42. Faust LR, el Benna J, Babior BM, Chanock SJ. The phosphorylation targets of p47phox, a subunit of the respiratory burst oxidase. Functions of the individual target serines as evaluated by site-directed mutagenesis. J Clin Invest 1995; 96: 1499-505.
43. Ago T, Kuribayashi F, Hiroaki H, Takeya R, Ito T, Kohda D, et al. Phosphorylation of p47phox directs phox homology domain from SH3 domain toward phosphoinositides, leading to phagocyte NADPH oxidase activation. Proc Natl Acad Sci USA 2003; 100: 4474-9.
44. Han CH, Freeman JL, Lee T, Motalebi SA, Lambeth JD. Regulation of the neutrophil respiratory burst oxidase. Identification of an activation domain in p67(phox). J Biol Chem 1998; 273: 16663-8.
45. Nisimoto Y, Motalebi S, Han CH, Lambeth JD. The p67(phox) activation domain regulates electron flow from NADPH to flavin in flavocytochrome b(558). J Biol Chem 1999; 274: 22999-3005.
46. Lopes LR, Dagher MC, Gutierrez A, Young B, Bouin AP, Fuchs A, et al. Phosphorylated p40phox as a negative regulator of NADPH oxidase. Biochemistry 2004; 43: 3723-30.
47. Sathyamoorthy M, de Mendez I, Adams AG, Leto TL. P40phox down-regulates NADPH oxidase activity through interactions with its SH3 domain. J Biol Chem 1997; 272: 9141-6.
48. Tamura M, Shiozaki I, Ono S, Miyano K, Kunihiro S, Sasaki T. p40phox as an alternative organizer to p47phox in Nox2 activation: A new mechanism involving an interaction with p22phox. FEBS Lett 2007; 581: 4533-8.
49. Tsunawaki S, Kagara S, Yoshikawa K, Yoshida LS, Kuratsuji T, Namiki H. Involvement of p40phox in activation of phagocyte NADPH oxidase through association of its carboxyl-terminal, but not its amino-terminal, with p67phox. J Exp Med 1996; 184: 893-902.
50. Koga H, Terasawa H, Nunoi H, Takeshige K, Inagaki F, Sumimoto H. Tetratricopeptide repeat (TPR) motifs of p67(phox) participate in interaction with the small GTPase Rac and activation of the phagocyte NADPH oxidase. J Biol Chem 1999; 274: 25051-60.
51. Suh YA, Arnold RS, Lassegue B, Shi J, Xu X, Sorescu D, et al. Cell transformation by the superoxide-generating oxidase mox1. Nature 1999; 401: 79-82.
52. Cheng G, Cao Z, Xu X, van Meir EG, Lambeth JD. Homologs of gp91phox: Cloning and tissue expression of nox3, nox4, and nox5. Gene 2001; 269: 131-40.
53. Martyn KD, Frederick LM, von Loehneysen K, Dinauer MC, Knaus UG. Functional analysis of nox4 reveals unique characteristics compared to other NADPH oxidases. Cell Signal 2006; 18: 69-82.
54. Kawahara T, Ritsick D, Cheng G, Lambeth JD. Point mutations in the proline-rich region of p22phox are dominant inhibitors of nox1- and nox2-dependent reactive oxygen generation. J Biol Chem 2005; 280: 31859-69.
55. 2+ activation of the NADPH oxidase 5 (nox5). J Biol Chem 2004; 279: 18583-91.
56. Geiszt M, Lekstrom K, Witta J, Leto TL. Proteins homologous to p47phox and p67phox support superoxide production by NAD (P)H oxidase 1 in colon epithelial cells. J Biol Chem 2003; 278: 20006-12.
57. Takeya R, Ueno N, Kami K, Taura M, Kohjima M, Izaki T, et al. Novel human homologues of p47phox and p67phox participate in activation of superoxide-producing NADPH oxidases. J Biol Chem 2003; 278: 25234-46.
58. Ago T, Kitazono T, Kuroda J, Kumai Y, Kamouchi M, Ooboshi H, et al. NAD(P)H oxidases in rat basilar arterial endothelial cells. Stroke 2005; 36: 1040-6.
59. Van Buul JD, Fernandez-Borja M, Anthony EC, Hordijk PL. Expression and localization of nox2 and nox4 in primary human endothelial cells. Antioxid Redox Signal 2005; 7: 308-17.
60. Babior BM. The NADPH oxidase of endothelial cells. IUBMB Life 2000; 50: 267-9.
61. Datla SR, Peshavariya H, Dusting GJ, Jiang F. Important role of nox4 type NADPH oxidase in angiogenic responses in human microvascular endothelial cells in vitro. Arterioscler Thromb Vasc Biol 2007; 27: 2319-24. Epub 2007 Aug 23.
62. BelAiba RS, Djordjevic T, Petry A, Diemer K, Bonello S, Banfi B, et al. Nox5 variants are functionally active in endothelial cells. Free Radic Biol Med 2007; 42: 446-59.
63. Hanna IR, Hilenski LL, Dikalova A, Taniyama Y, Dikalov S, Lyle A, et al. Functional association of nox1 with p22phox in vascular smooth muscle cells. Free Radic Biol Med 2004; 37: 1542-9.
64. Moe KT, Aulia S, Jiang F, Chua YL, Koh TH, Wong MC, et al. Differential upregulation of nox homologues of NADPH oxidase by tumor necrosis factor-alpha in human aortic smooth muscle and embryonic kidney cells. J Cell Mol Med 2006; 10: 231-9.
65. Lassegue B, Sorescu D, Szocs K, Yin Q, Akers M, Zhang Y, et al. Novel gp91phox homologues in vascular smooth muscle cells: Nox1 mediates angiotensin ii-induced superoxide formation and redox-sensitive signaling pathways. Circ Res 2001; 88: 888-94.
66. Ambasta RK, Kumar P, Griendling KK, Schmidt HH, Busse R, Brandes RP. Direct interaction of the novel nox proteins with p22phox is required for the formation of a functionally active NADPH oxidase. J Biol Chem 2004; 279: 45935-41.
67. Wang HD, Pagano PJ, Du Y, Cayatte AJ, Quinn MT, Brecher P, et al. Superoxide anion from the adventitia of the rat thoracic aorta inactivates nitric oxide. Circ Res 1998; 82: 810-8.
68. Pagano PJ, Clark JK, Cifuentes-Pagano ME, Clark SM, Callis GM, Quinn MT. Localization of a constitutively active, phagocyte-like NADPH oxidase in rabbit aortic adventitia: Enhancement by angiotensin ii. Proc Natl Acad Sci U S A 1997; 94: 14483-8.
69. Cucoranu I, Clempus R, Dikalova A, Phelan PJ, Ariyan S, Dikalov S, et al. NAD(P)H oxidase 4 mediates transforming growth factor-{beta} 1-induced differentiation of cardiac fibroblasts into myofibroblasts. Circ Res 2005; 97: 900-7.
70. Lyle AN, Griendling KK. Modulation of vascular smooth muscle signaling by reactive oxygen species. Physiology (Bethesda) 2006; 21: 269-80.
71. Touyz RM, Yao G, Viel E, Amiri F, Schiffrin EL. Angiotensin ii and endothelin-1 regulate MAP kinases through different redox-dependent mechanisms in human vascular smooth muscle cells. J Hypertens 2004; 22: 1141-9.
72. Hingtgen SD, Tian X, Yang J, Dunlay SM, Peek AS, Wu Y, et al. Nox2-containing NADPH oxidase and Akt activation play a key role in angiotensin ii-induced cardiomyocyte hypertrophy. Physiol Genomics 2006; 26: 180-91.
73. Moldovan L, Moldovan NI, Sohn RH, Parikh SA, Goldschmidt-Clermont PJ. Redox changes of cultured endothelial cells and actin dynamics. Circ Res 2000; 86: 549-57.
74. Wu RF, Xu YC, Ma Z, Nwariaku FE, Sarosi GA Jr Terada LS. Subcellular targeting of oxidants during endothelial cell migration. J Cell Biol 2005; 171: 893-904.
75. Colavitti R, Pani G, Bedogni B, Anzevino R, Borrello S, Waltenberger J, et al. Reactive oxygen species as downstream mediators of angiogenic signaling by vascular endothelial growth factor receptor-2/kdr. J Biol Chem 2002; 277: 3101-8.
76. Chen JX, Zeng H, Tuo QH, Yu H, Meyrick B, Aschner JL. NADPH oxidase modulates myocardial Akt, Erk1/2 activation, and an-giogenesis after hypoxia-reoxygenation. Am J Physiol Heart Circ Physiol 2007; 292: H1664-74.
77. Li JM, Fan LM, George VT, Brooks G. Nox2 regulates endothelial cell cycle arrest and apoptosis via p21cip1 and p53. Free Radic Biol Med 2007; 43: 976-86.
78. Shukla N, Jones R, Persad R, Angelini GD, Jeremy JY. Effect of sildenafil citrate and a nitric oxide donating sildenafil derivative, NCX 911, on cavernosal relaxation and superoxide formation in hypercholesterolaemic rabbits. Eur J Pharmacol 2005; 517: 224-31.
79. Koupparis AJ, Jeremy JY, Muzaffar S, Persad R, Shukla N. Sildenafil inhibits the formation of superoxide and the expression of gp47phox NAD[P]H oxidase induced by the thromboxane a2 mimetic, u46619, in corpus cavernosal smooth muscle cells. BJU Int 2005; 96: 423-7.
80. Teixeira CE, Priviero FB, Webb RC. Effects of 5-cyclopropyl-2-[1-(2-fluoro-benzyl)-1h-pyrazolo [3,4-b]pyridine-3-yl] pyrimidin-4-ylamine (bay 41-2272) on smooth muscle tone, soluble guanylyl cyclase activity, and NADPH oxidase activity/expression in corpus cavernosum from wild-type, neuronal, and endothelial nitric-oxide synthase null mice. J Pharmacol Exp Ther 2007; 322: 1093-102.
81. Hotston MR, Jeremy JY, Bloor J, Koupparis A, Persad R, Shukla N. Sildenafil inhibits the up-regulation of phosphodiesterase type 5 elicited with nicotine and tumour necrosis factor-alpha in cavernosal vascular smooth muscle cells: Mediation by superoxide. BJU Int 2007; 99: 612-8.
82. Jin L, Lagoda G, Leite R, Webb RC, Burnett AL. NADPH oxidase activation: A mechanism of hypertension-associated erectile dysfunction. J Sex Med 2007 (in press).