Nutritional biochemistry of cellular glutathione

Journal of Nutritional Biochemistry

Volumn 8, Issue 12, 1997, Pages 660-672

  Sen, Chandan K ^a  

^a UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

AIDS; Lipoic acid; N acetylcysteine; Redox; Supplement; Thiols

Indexed keywords

2 OXO 4 THIAZOLIDINECARBOXYLIC ACID; ACETYLCYSTEINE; ANTIOXIDANT; CYSTEINE; DIHYDROLIPOATE; GLUTATHIONE; GLUTATHIONE DISULFIDE; THIOCTIC ACID;

ACQUIRED IMMUNE DEFICIENCY SYNDROME; BIOCHEMISTRY; CELL LEVEL; CLINICAL TRIAL; DRUG MECHANISM; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; INTRAPERITONEAL DRUG ADMINISTRATION; MOLECULAR BIOLOGY; NONHUMAN; NUTRITION; REVIEW; SIGNAL TRANSDUCTION;

ANIMALIA; HUMAN IMMUNODEFICIENCY VIRUS;

EID: 0031545084     PISSN: 09552863     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0955-2863(97)00113-7     Document Type: Review

References (178)

1. 1 De Rey-Pailhade, J. (1888). Sur un corps d'origine organique hydrogenant le soufre a froid. Compte rendus hebdomadaire séances de l'Académied des sciences 106, 1683-1684
2. 2 De Rey-Pailhade, J. (1888). Nouvelles recherches physiologiques sur la substance organique hydrogenant le soufre a froid. Compte rendus hebdomadaire séances de l'Académied des sciences 107, 43-44
3. 3 Hopkins, F.G. (1921). On an autoxidiasable constituent of the cell. Biochem. J. 15, 286-305
4. 4 Hopkins, F.G. (1929). On glutathione: a reinvestigation. J. Biol. Chem. 84, 269-320
5. 5 Kendall, E.C., McKenzie, B.F., and Mason, H.L. (1929). A study of glutathione. I. Its preparation in crystalline form and its identification. Journal of Biological Chemistry 84, 657-674
6. 6 Meister, A. (1981). On the cycles of glutathione metabolism and transport. Curr. Top. Cell Regul. 18, 21-58
7. 7 Meister, A. (1984). New aspects of glutathione biochemistry and transport-selective alteration of glutathione metabolism. Nutr. Rev. 42, 397-410
8. 8 Meister, A. (1984). New aspects of glutathione biochemistry and transport: selective alteration of glutathione metabolism. Fed. Proc. 43, 3031-3042
9. 9 Meister, A. and Anderson, M.E. (1983). Glutathione. Annu. Rev. Biochem. 52, 711-760
10. 10 Meister, A. (1988). Glutathione metabolism and its selective modification. J. Biol. Chem. 263, 17205-17208
11. 11 Meister, A. (1995). Glutathione metabolism. Methods Enzymol. 251, 3-7
12. 12 Gilbert, H.F. (1995). Thiol/disulfide exchange equilibria and disulfide bond stability. Methods Enzymol. 251, 8-28
13. 13 Sen, C.K. and Hanninen, O. (1994). Physiological antioxidants. In Exercise and oxygen toxicity (C.K. Sen, L. Packer, and O. Hanninen, eds.) pp. 89-126, Elsevier Science Publishers B.V., Amsterdam
14. 14 Meister, A. (1992). On the antioxidant effects of ascorbic acid and glutathione. Biochem. Pharmacol. 44, 1905-1915
15. 15 Meister, A. (1992). Biosynthesis and functions of glutathione, an essential biofactor. J. Nutr. Sci. Vitaminol. (Tokyo) Spec No, 1-6
16. 16 Thomas, J.P., Maiorino, M., Ursini, F., and Girotti, A.W. (1990). Protective action of phospholipid hydroperoxide glutathione peroxidase against membrane-damaging lipid peroxidation. In situ reduction of phospholipid and cholesterol hydroperoxides. J. Biol. Chem. 265, 454-461
17. 17 Hayes, J.D. and Pulford, D.J. (1995). The glutathione S-transferase supergene family: regulation of GST and the contribution of the isoenzymes to cancer chemoprotection and drug resistance. Crit. Rev. Biochem. Mol. Biol. 30, 445-600
18. 18 DeLeve, L.D. and Kaplowitz, N. (1990). Importance and regulation of hepatic glutathione. Semin. Liver Dis. 10, 251-266
19. 19 Kehrer, J.P. and Lund, L.G. (1994). Cellular reducing equivalents and oxidative stress. Free Radic. Biol. Med. 17, 65-75
20. 20 Roy, S., Sen, C.K., Tritschler, H., and Packer, L. (1997). Modulation of cellular reducing equivalent homeostasis by alpha-lipoic acid: mechanisms and implications for diabetes and ischemic injury. Biochem. Pharmacol. 53, 393-399
21. 21 Richman, P.G. and Meister, A. (1975). Regulation of gamma-glutamyl-cysteine synthetase by nonallosteric feedback inhibition by glutathione. J. Biol. Chem. 250, 1422-1426
22. 22 Gali, R.R. and Board, P.G. (1997). Identification of an essential cysteine residue in human glutathione synthase. Biochem. J. 321, 207-210
23. 23 Packer, L., Witt, E.H., and Tritschler, H.J. (1995). alpha-Lipoic acid as a biological antioxidant. Free Radic. Biol. Med. 19, 227-250
24. 24 Burk, R.F. (1983). Biological activity of selenium. Annu. Rev. Nutr. 3, 53-70
25. 25 Yin, S.A., Sato, I., Hosokawa, Y., Niizeki, S., Tojo, H., and Yamaguchi, K. (1991). The necessity of dietary vitamin B6 to selenium biopotency for tissue selenium and glutathione peroxidase in rats. J. Nutr. Sci. Vitaminol. (Tokyo) 37, 509-516
26. 26 Sen, C.K. and Packer, L. (1997). Thiol homeostasis and supplementation in physical exercise. Am. J. Clin. Nutr., (in press)
27. 27 Bowry, V.W., Ingold, K.U., and Stocker, R. (1992). Vitamin E in human low-density lipoprotein. When and how this becomes a pro-oxidant. Biochem. J. 288, 341-344
28. 28 Kuzuya, M., Naito, M., Funaki, C., Hayashi, T., Asai, K., and Kuzuya, F. (1989). Protective role of intracellular glutathione against oxidized low density lipoprotein in cultured endothelial cells. Biochem. Biophys. Res. Commun. 163, 1466-1472
29. 29 Pascoe, G.A. and Reed, D.J. (1989). Cell calcium, vitamin E, and the thiol redox system in cytotoxicity. Free Radical Bio. Med. 6, 209-224
30. 30 Marcus, S.R., Chandrakala, M.V., and Nadiger, H.A. (1993). Interaction between vitamin E and glutathione in rat brain - effect of acute alcohol administration. J. Nutr. Biochem. 4, 336-341
31. 31 Reed, D.J. (1990). Status of calcium and thiols hepatocellular injury by oxidative stress. Semin. Liver Dis. 10, 285-292
32. 32 Johnston, C.S., Meyer, C.S., and Srilakshmi, J.C. (1993). Vitamin C elevates red blood cell glutathione in healthy adults. Am. J. Clin. Nutr. 58, 103-105
33. 33 Martensson, J. and Meister, A. (1992). Glutathione deficiency increases hepatic ascorbic acid synthesis in adult mice. Proc. Natl. Acad. Sci. USA 89, 11566-11568
34. 34 Thomas, W.R. and Holt, P.G. (1978). Vitamin C and immunity: An assessment of the evidence. Clin. Exp. Immunol. 32, 370-379
35. 35 Block, G. (1991). Epidemiologic evidence regarding vitamin C and cancer. Am. J. Clin. Nutr. 54, 1310S-1314S
36. 36 Chen, L.H. and Thacker, R.R. (1984). An increase in glutathione peroxidase activity induced by high supplementation of vitamin C in rats. Nutr. Res. 4, 657-664
37. 37 Halliwell, B. and Gutteridge, J.M.C. (1993). Free Radicals Biology and Medicine, pp. 543, Clarendon Press, Oxford
38. 38 Sen, C.K., Packer, L., and Hanninen, O. (1994). Exercise and Oxygen Toxicity, pp. 536, Elsevier Science Publishers B.V., Amsterdam
39. 39 Sen, C.K. and Packer, L. (1996). Antioxidant and redox regulation of gene transcription. Faseb. J. 10, 709-720
40. 40 Droge, W., Schulze-Osthoff, K., Mihm, S., Galter, D., Schenk, H., Eck, H.P., Roth, S., and Gmunder, H. (1994). Functions of glutathione and glutathione disulfide in immunology and immuno-pathology. Faseb. J. 8, 1131-1138
41. 41 Janssen, Y.M., Heintz, N.H., and Mossman, B.T. (1995). Induction of c-fos and c-jun protooncogene expression by asbestos is ameliorated by N-acetyl-L-cysteine in mesothelial cells. Cancer Res. 55, 2085-2089
42. 42 Gaiter, D., Mihm, S., and Droge, W. (1994). Distinct effects of glutathione disulphide on the nuclear transcription factor kappa B and the activator protein-1. Eur. J. Biochem. 221, 639-648
43. 43 Ghibelli, L., Coppola, S., Rotilio, G., Lafavia, E., Maresca, V., and Ciriolo, M.R. (1995). Nonoxidative loss of glutathione in apoptosis via GSH extrusion. Biochem. Biophys. Res. Commun. 216, 313-320
44. 44 van den Dobbelsteen, D.J., Nobel, C.S.I., Schlegel, J., Cotgreave, I.A., Orrenius, S., and Slater, A.F. (1996). Rapid and specific efflux of reduced glutathione during apoptosis induced by anti-Fas/APO-1 antibody. J. Biol. Chem. 271, 15420-15427
45. 45 Beaver, J.P. and Waring, P. (1995). A decrease in intracellular glutathione concentration precedes the onset of apoptosis in murine thymocytes. Eur. J. Cell. Biol. 68, 47-54
46. 46 Chiba, T., Takahashi, S., Sato, N., Ishii, S., and Kikuchi, K. (1996). Fas-mediated apoptosis is modulated by intracellular glutathione in human T cells. Eur. J. Immunol. 26, 1164-1169
47. 47 Iyori, H., Hirono, A., Kobayashi, N., Ishitoya, N., Akatsuka, J., Kanno, H., Fujii, H., and Miwa, S. (1996). [Glutathione synthetase deficiency]. Rinsho Ketsueki 37, 329-334
48. 48 Droge, W., Eck, H.P., and Mihm, S. (1992). HIV-induced cysteine deficiency and T-cell dysfunction - a rationale for treatment with N-acetylcysteine. Immunology Today 13, 211-214
49. 49 Estrela, J.M., Gil, F., Vila, J.M., and Vina, J. (1988). Alpha-adrenergic modulation of glutathione metabolism in isolated rat hepatocytes. Am. J. Physiol. 255, E801-805
50. 50 Harbison, R.D., James, R.C., and Roberts, S.M. (1991). Hepatic glutathione suppression by the alpha-adrenoreceptor stimulating agents phenylephrine and clonidine. Toxicology 69, 279-290
51. 51 Lu, S.C., Kuhlenkamp, J., Garcia-Ruiz, C., and Kaplowitz, N. (1991). Hormone-mediated down-regulation of hepatic glutathione synthesis in the rat. J. Clin. Invest. 88, 260-269
52. 52 Lu, S.C., Ge, J.L., Kuhlenkamp, J., and Kaplowitz, N. (1992). Insulin and glucocorticoid dependence of hepatic gamma-glutamyl-cysteine synthetase and glutathione synthesis in the rat. Studies in cultured hepatocytes and in vivo. J. Clin. Invest. 90, 524-532
53. 53 Ogino, T., Packer, L., and Maguire, J.J. (1997). Neutrophil antioxidant capacity during the respiratory burst: Loss of glutathione induced by chloramine. Free Radic. Biol. Med. 23, 445-452
54. 54 Bilzer, M. and Lauterburg, B.H. (1991). Glutathione metabolism in activated human neutrophils: stimulation of glutathione synthesis and consumption of glutathione by reactive oxygen species. Eur. J. Clin. Invest. 21, 316-322
55. 55 Bilzer, M. and Lauterburg, B.H. (1991). Effects of hypochlorous acid and chloramines on vascular resistance, cell integrity, and biliary glutathione disulfide in the perfused rat liver: Modulation by glutathione. J. Hepatol. 13, 84-89
56. 56 Sen, C.K. (1995). Oxidants and antioxidants in exercise. J. Appl. Physiol. 79, 675-686
57. 57 Sen, C.K., Marin, E., Kretzschmar, M., and Hanninen, O. (1992). Skeletal muscle and liver glutathione homeostasis in response to training, exercise, and immobilization. J. Appl. Physiol. 73, 1265-1272
58. 58 Sen, C.K., Rankinen, T., Vaisanen, S., and Rauramaa, R. (1994). Oxidative stress after human exercise: Effect of N-acetylcysteine supplementation [published erratum appears in J. Appl. Physiol. 1994 77(5) and in 1994 77(6)]. J. Appl. Physiol. 76, 2570-2577
59. 59 Sen, C.K., Roy, S., and Packer, L. (1997). Therapeutic potential of the antioxidant and redox properties of alpha-lipoic acid. In: Oxidative Stress Cancer, AIDS and Neurodegenerative Diseases (L. Montagnier, R. Olivier, C. Pasquier, eds.), pp. 251-267, Marcel Dekker Inc., New York
60. 60 Golden, M.H. and Ramdath, D. (1987). Free radicals in the pathogenesis of kwashiorkor. Proc. Nutr. Soc. 46, 53-68
61. 61 Gulick, A.M. and Fahl, W.E. (1995). Mammalian glutathione S-transferase: Regulation of an enzyme system to achieve chemotherapeutic efficacy. Pharmacol. Ther. 66, 237-257
62. 62 Otto, D.M., Sen, C.K., Casley, W.L., and Moon, T.W. (1996). Glutathione regulates 3,3′,4,4′-tetrachlorobiphenyl induced cytochrome P450 metabolism: Evidence for a cross-talk between the two major detoxication pathways. Biochem. Mol. Biol. Int. 38, 1127-1133
63. 63 Sipes, I.G., Wiersma, D.A., and Armstrong, D.J. (1986). The role of glutathione in the toxicity of xenobiotic compounds: Metabolic activation of 1,2-dibromoethane by glutathione. Adv. Exp. Med. Biol. 197, 457-467
64. 64 Mantle, T.J. (1995). The glutathione S-transferase multigene family: a paradigm for xenobiotic interactions. Biochem. Soc. Trans. 23, 423-425
65. 65 Jones, D.P., Brown, L.A., and Sternberg, P. (1995). Variability in glutathione-dependent detoxication in vivo and its relevance to detoxication of chemical mixtures. Toxicology 105, 267-274
66. 66 Dekant, W. (1997). Glutathione-dependent bioactivation and renal toxicity of xenobiotics. Recent Results Cancer Res. 143, 77-87
67. 67 Manautou, J.E., Tveit, A., Hoivik, D.J., Khairallah, E.A., and Cohen, S.D. ( 1996). Protection by clofibrate against acetaminophen hepatotoxicity in male CD-1 mice is associated with an early increase in biliary concentration of acetaminophen-glutathione adducts. Toxicol. Appl. Pharmacol. 140, 30-38
68. 68 Dalhoff, K. and Poulsen, H.E. (1993). Synthesis rates of glutathione and activated sulphate (PAPS) and response to cysteine and acetaminophen administration in glutathione-depleted rat hepatocytes. Biochem. Pharmacol. 46, 1295-1297
69. 69 Richie, J.P., Jr., Lang, C.A., and Chen, T.S. (1992). Acetaminophen-induced depletion of glutathione and cysteine in the aging mouse kidney. Biochem. Pharmacol. 44, 129-135
70. 70 Meister, A. and Larsson, A. (1994). Glutathione synthetase deficiency and other disorders of the γ-glutamyl cycle. In: The Metabolic Basis of Inherited Disease (C.R. Scriver, A.L. Beaudet, W.S. Sly, and D. Valle, eds.). pp. 1461-1477, McGraw Hill, New York
71. 71 Harman, D. (1988). Free radicals in aging. Mol. Cell. Biochem. 84, 155-161
72. 72 Harman, D. (1988). The aging process. Basic Life Sci. 49, 1057-1065
73. 73 Maruyama, E., Kojima, K., Higashi, T., and Sakamoto, Y. (1968). Effect of diet on liver glutathione and glutathione reductase. J. Biochem. (Tokyo) 63, 398-399
74. 74 Jaeger, R.J., Conolly, R.B., and Murphy, S.D. (1973). Diurnal variation of hepatic glutathione concentration and its correlation with 1,1-dichloroethylene inhalation toxicity in rats. Res. Commun. Chem. Pathol. Pharmacol. 6, 465-471
75. 75 Tateishi, N., Higashi, T., Shinya, S., Naruse, A., and Sakamoto, Y. (1974). Studies on the regulation of glutathione level in rat liver. J. Biochem. (Tokyo) 75, 93-103
76. 76 Tateishi, N., Higashi, T., Naruse, A., Nakashima, K., and Shiozaki, H. (1977). Rat liver glutathione: Possible role as a reservoir of cysteine. J. Nutr. 107, 51-60
77. 77 Cho, E.S., Sahyoun, N., and Stegink, L.D. (1981). Tissue glutathione as a cyst(e)ine reservoir during fasting and refeeding of rats. J. Nutr. 111, 914-922
78. 78 Jaeschke, H. and Wendel, A. (1985). Manipulation of mouse organ glutathione contents I: enhancement by oral administration of butylated hydroxyanisole and butylated hydroxytoluene. Toxicology 36, 77-85
79. 79 Bauman, P.F., Smith, T.K., and Bray, T.M. (1988). The effect of dietary protein and sulfur amino acids on hepatic glutathione concentration and glutathione-dependent enzyme activities in the rat. Can. J. Physiol. Pharmacol. 66, 1048-1052
80. 80 Bauman, P.F., Smith, T.K., and Bray, T.M. (1988). Effect of dietary protein deficiency and L-2-oxothiazolidine-4-carboxylate on the diurnal rhythm of hepatic glutathione in the rat. J. Nutr. 118, 1049-1054
81. 81 Meister, A. (1991). Glutathione deficiency produced by inhibition of its synthesis, and its reversal; applications in research and therapy. Pharmacol. Ther. 51, 155-194
82. 82 Vina, J., Perez, C., Furukawa, T., Palacin, M., and Vina, J.R. (1989). Effect of oral glutathione on hepatic glutathione levels in rats and mice. Br. J. Nutr. 62, 683-691
83. 83 Martensson, J., Jain, A., and Meister, A. (1990). Glutathione is required for intestinal function. Proc. Natl. Acad. Sci. USA 87, 1715-1719
84. 84 Hagen, T.M., Wierzbicka, G.T., Bowman, B.B., Aw, T.Y., and Jones, D.P. (1990). Fate of dietary glutathione: disposition in the gastrointestinal tract. Am. J. Physiol. 259, G530-535
85. 85 Aw, T.Y., Wierzbicka, G., and Jones, D.P. (1991). Oral glutathione increases tissue glutathione in vivo. Chem. Biol. Interact. 80, 89-97
86. 86 Sen, C.K., Atalay, M., and Hanninen, O. (1994). Exercise-induced oxidative stress: glutathione supplementation and deficiency. J. Appl. Physiol 77, 2177-2187
87. 87 Levy, E.J., Anderson, M.E., and Meister, A. (1993). Transport of glutathione diethyl ester into human cells. Proc. Natl. Acad. Sci. USA 90, 9171-9175
88. 88 Anderson, M.E. and Meister, A. (1989). Glutathione monoesters. Anal. Biochem. 183, 16-20
89. 89 Anderson, M.E., Levy, E.J., and Meister, A. (1994). Preparation and use of glutathione monoesters. Methods Enzymol. 234, 492-499
90. 90 Puri, R.N. and Meister, A. (1983). Transport of glutathione, as gamma-glutamylcysteinylglycyl ester, into liver and kidney. Proc. Natl. Acad. Sci. USA 80, 5258-5260
91. 91 Nishiuch, Y., Sasaki, M., Nakayasu, M., and Oikawa, A. (1976). Cytotoxicity of cysteine in culture media. In Vitro 12, 635-638
92. 92 Olney, J.W. and Ho, O.L. (1970). Brain damage in infant mice following oral intake of glutamate, aspartate or cysteine. Nature 227, 609-611
93. 93 Olney, J.W., Ho, O.L., and Rhee, V. (1971). Cytotoxic effects of acidic and sulphur containing amino acids on the infant mouse central nervous system. Exp. Brain Res. 14, 61-76
94. 94 Olney, J.W., Ho, O.L., Rhee, V., and Schainker, B. (1972). Cysteine-induced brain damage in infant and fetal rodents. Brain Res. 45, 309-313
95. 95 Karlsen, R.L., Grofova, I., Malthe-Sorenssen, D., and Fonnum, F. (1981). Morphological changes in rat brain induced by L-cysteine injection in newborn animals. Brain Res. 208, 167-180
96. 96 Takada, A. and Bannai, S. (1984). Transport of cystine in isolated rat hepatocytes in primary culture. J. Biol. Chem. 259, 2441-2445
97. 97 Loven, D., Schedl, H., Wilson, H., Daabees, T.T., Stegink, L.D., Diekus, M., and Oberley, L. (1986). Effect of insulin and oral glutathione on glutathione levels and superoxide dismutase activities in organs of rats with streptozocin-induced diabetes. Diabetes 35, 503-507
98. 98 Denno, R., Rounds, J.D., Faris, R., Holejko, L.B., and Wilmore, D.W. (1996). Glutamine-enriched total parenteral nutrition enhances plasma glutathione in the resting state. J. Surg. Res. 61, 35-38
99. 99 Hong, R.W., Rounds, J.D., Helton, W.S., Robinson, M.K., and Wilmore, D.W. (1992). Glutamine preserves liver glutathione after lethal hepatic injury. Ann. Surg. 215, 114-119
100. 100 Williamson, J.M and Meister, A. (1981). Stimulation of hepatic glutathione formation by administration of L-2-oxothiazolidine-4-carboxylate, a 5-oxo-L-prolinase substrate. Proc. Natl. Acad. Sci. USA 78, 936-939
101. 101 Williamson, J.M. and Meister, A. (1982). New substrates of 5-oxo-L-prolinase. J. Biol. Chem. 257, 12039-12042
102. 102 Williamson, J.M., Boettcher, B., and Meister, A. (1982). Intracellular cysteine delivery system that protects against toxicity by promoting glutathione synthesis. Proc. Natl. Acad. Sci. USA 79, 6246-6249
103. 103 Williamson, J.M. and Meister, A. (1982). Effect of sulfhydryl group modification on the activities of 5-oxo-L-prolinase. J. Biol. Chem. 257, 9161-9172
104. 104 Porta, P., Aebi, S., Summer, K., and Lauterburg, B.H. (1991). L-2-oxothiazolidine-4-carboxylic acid, a cysteine prodrug: pharmacokinetics and effects on thiols in plasma and lymphocytes in human. J. Pharmacol. Exp. Ther. 257, 331-334
105. 105 Kalayjian, R.C., Skowron, G., Emgushov, R.T., Chance, M., Spell, S.A., Borum, P.R., Webb, L.S., Mayer, K.H., Jackson, J.B., Yen-Lieberman, B., et al. (1994). A phase I/II trial of intravenous L-2-oxothiazolidine-4-carboxylic acid (procysteine) in asymptomatic HIV-infected subjects. J. Acquir. Immune Defic. Syndr. 7, 369-374
106. 106 Akerlund, B., Jarstrand, C., Lindeke, B., Sonnerborg, A., Akerblad, A.C., and Rasool, O. (1996). Effect of N-acetylcysteine (NAC) treatment on HIV-1 infection: A double-blind placebo-controlled trial. Eur. J. Clin. Pharmacol. 50, 457-461
107. 107 Aruoma, O.I., Halliwell, B., Hoey, B.M., and Butler, J. (1989). The antioxidant action of N-acetylcysteine: Its reaction with hydrogen peroxide, hydroxyl radical, superoxide, and hypochlorous acid. Free Radic. Biol. Med. 6, 593-597
108. 108 Atalay, M., Marnila, P., Lilius, E.M., Hanninen, O., and Sen, C.K. (1996). Glutathione-dependent modulation of exhausting exercise-induced changes in neutrophil function of rats. Eur. J. Appl. Physiol. 74, 342-347
109. 109 Borgstrom, L., Kagedal, B., and Paulsen, O. (1986). Pharmacokinetics of N-acetylcysteine in man. Eur. J. Clin. Pharmacol. 31, 217-222
110. 110 Ferrari, G., Yan, C.Y., and Greene, L.A. (1995). N-acetylcysteine (D-and L-stereoisomers) prevents apoptotic death of neuronal cells. J. Neurosci. 15, 2857-2866
111. 111 Holdiness, M.R. (1991). Clinical pharmacokinetics of N-acetylcysteine. Clinical Pharmacokinetics 20, 123-134
112. 112 Huupponen, M.R., Makinen, L.H., Hyvonen, P.M., Sen, C.K., Rankinen, T., Vaisanen, S., and Rauramaa, R. (1995). The effect of N-acetylcysteine on exercise-induced priming of human neutrophils. A chemiluminescence study. Int. J. Sports Med. 16, 399-403
113. 113 Issels, R.D., Nagele, A., Eckert, K.G., and Wilmanns, W. (1988). Promotion of cystine uptake and its utilization for glutathione biosynthesis induced by cysteamine and N-acetylcysteine. Biochem. Pharmacol. 37, 881-888
114. 114 van Zandwijk, N. (1995). N-acetylcysteine (NAC) and glutathione (GSH): Antioxidant and chemopreventive properties, with special reference to lung cancer. J. Cell. Biochem. Suppl. 22, 24-32
115. 115 Packer, L., Roy, S., and Sen, C.K. (1997). Alpha-lipoic acid: A metabolic antioxidant and potential redox modulator of transcription. Adv. Pharmacol. 38, 79-101
116. 116 Sen, C.K., Roy, S., Han, D., Packer, L. (1997). Regulation of cellular thiols in human lymphocytes by alpha-lipoic acid: A flow cytometric analysis. Free Radic. Biol. Med. 22, 1241-1257
117. 117 Sjodin, K., Nilsson, E., Hallberg, A., and Tunek, A. (1989). Metabolism of N-acetyl-L-cysteine. Some structural requirements for the deacetylation and consequences for the oral bioavailability. Biochem. Pharmacol. 38, 3981-3985
118. 118 Olsson, B., Johansson, M., Gabrielsson, J., and Bolme, P. (1988). Pharmacokinetics and bioavailability of reduced and oxidized N-acetylcysteine. Eur. J. Clin. Pharmacol. 34, 77-82
119. 119 Chasseaud, L.F. (1974). Reaction with electrophiles after enzyme-catalysed deacetylation of N-acetylcysteine. Biochem. Pharmacol. 23, 1133-1134
120. 120 Bonanomi, L. and Gazzaniga, A. (1980). Toxicological, pharmacokinetic and metabolic studies on acetylcysteine. Eur. J. Respir. Dis. Suppl. 111, 45-51
121. 121 Keith, R.A., Jardine, I., Kerremans, A., and Weinshilboum, R.M. (1984). Human erythrocyte membrane thiol methyltransferase. S-methylation of captopril, N-acetylcysteine, and 7 alpha-thiospirolactone. Drug Metab. Dispos. 12, 717-724
122. 122 Stokstad, E., Broquist, H., and Patterson, E. (1953). Role of protagon in animal nutrition. Fed. Proc. 12, 430
123. 123 DeBusk, C.B. and Williams, R.J. (1955). Effect of lipoic acid on the growth rate of young chicks and rats. Arch. Biochem. Biophys. 55, 587
124. 124 Fujiwara, K., Okamura-Ikeda, K., and Motokawa, Y. (1991). Lipoylation of H-protein of the glycine cleavage system. FEBS Letters 293, 115-118
125. 125 Lodge, L., Handelman, G.J., Konishi, T., Matsugo, S.. Mathur, V.V., and Packer, L. (1997). Natural sources of lipoic acid: Determination of lipoyllysine released from protease-digested tissues by high performance liquid chromatography incorporating electrochemical detection. J. Appl. Nutr. (in press).
126. 126 Haramaki, N., Han, D., Handelman, G.J., Tritschler, H.J., and Packer, L. (1997). Cytosolic and mitochondrial systems for NADH-and NADPH-dependent reduction of α-lipoic acid. Free Radic. Biol. Med. 22, 535-542
127. 127 Pick, U., Haramaki, N., Constantinescu, A., Handelman, G.J., Tritschler, H.J., and Packer, L. (1995). Glutathione reductase and lipoamide dehydrogenase have opposite stereospecificities for alpha-lipoic acid enantiomers. Biochem. Biophys. Res. Commun. 206, 724-730
128. 128 Arner, E.S.J., Nordberg, J., and Holmgren, A. (1996). Efficient reduction of lipoamide and lipoic acid by mammalian thioredoxin reductase. Biochem. Biophys. Res. Commun. 225, 268-274
129. 129 Peinado, J., Seis, H., Akerboom, T.P.M. (1989). Hepatic lipoate uptake. Arch. Biochem. Biophys. 273, 389-395
130. 130 Busse, E., Zimmer, G., Schopohl, B., and Kornhuber, B. (1992). Influence of alpha-lipoic acid on intracellular glutathione in vitro and in vivo. Arzneimittelforschung 42, 829-831
131. 131 Handelman, G.J., Han, D., Tritschler, H., and Packer, L. (1994). Alpha-lipoic acid reduction by mammalian cells to the dithiol form, and release into the culture medium. Biochem. Pharmacol. 47, 1725-1730
132. 132 Watanabe, H. and Bannai, S. (1987). Induction of cystine transport activity in mouse peritoneal macrophages. J. Exp. Med. 165, 628-640
133. 133 Han, D., Handelman, G., Marcocci, L., Sen, C.K., Roy, S., Kobuchi, H., Flohe, L., and Packer, L. (1997). Lipoic acid increases de novo synthesis of cellular glutathione by improving cysteine utilization. Biofactors 6, 321-338
134. 134 Eck, H.P., Gmunder, H., Hartmann, M., Petzoldt, D., Daniel, V., and Droge, W. (1989). Low concentrations of acid-soluble thiol (cysteine) in the blood plasma of HIV-1-infected patients. Biol. Chem. Hoppe Seyler 370, 101-108
135. 135 Eck, H.P., Frey, H., and Droge, W. (1989). Elevated plasma glutamate concentrations in HIV-1-infected patients may contribute to loss of macrophage and lymphocyte functions. Int. Immunol. 1, 367-372
136. 136 Roederer, M., Staal, F.J., Osada, H., Herzenberg, L.A., and Herzenberg, L.A. (1991). CD4 and CD8 T cells with high intracellular glutathione levels are selectively lost as the HIV infection progresses. Int. Immunol. 3, 933-937
137. 137 Staal, F.J., Roederer, M., Herzenberg, L.A., Herzenberg, L.A. (1992). Glutathione and immunophenotypes of T and B lymphocytes in HIV-infected individuals. Ann. NY Acad. Sci. 651, 453-463
138. 138 Staal, F.J.T., Roederer, M., Israelski, D.M., Bubp, J., Mole, L.A., McShane, D., Deresinski, S.C., Ross, W., Sussman, H., Raju, P.A., et al. (1992). Intracellular glutathione in T-cell subsets decrease in HIV infected individuals. AIDS Research Human Retroviruses 2, 305-311
139. 139 Ho, W.Z. and Douglas, S.D. (1992). Glutathione and N-acetylcysteine suppression of human immunodeficiency virus replication in human monocyte/macrophages in vitro. AIDS Res. Hum. Retroviruses 8, 1249-1253
140. 140 Levy, E.M., Wu, J., Salibian, M., and Black, P.H. (1992). The effect of changes in thiol subcompartments on T-cell colony formation and cell cycle progression: Relevance to AIDS. Cell Immunol. 140, 370-380
141. 141 Kalebic, T., Kinter, A., Poli, G., Anderson, M.E., Meister, A., and Fauci, A.S. (1991). Suppression of human immunodeficiency virus expression in chronically infected monocytic cells by glutathione, glutathione ester, and N-acetylcysteine. Proc. Natl. Acad. Sci. USA 88, 986-990
142. 142 Mihm, S., Ennen, J., Pessara, U., Kurth, R., and Droge, W. (1991). Inhibition of HIV-1 replication and NF-kappa B activity by cysteine and cysteine derivatives. Aids 5, 497-503
143. 143 Raju, P.A., Herzenberg, L.A., Herzenberg, L.A., and Roederer, M. (1994). Glutathione precursor and antioxidant activities of N-acetylcysteine and oxothiazolidine carboxylate compared in in vitro studies of HIV replication. AIDS Res. Hum. Retroviruses 10, 961-967
144. 144 Roederer, M., Raju, P.A., Staal, F.J., Herzenberg, L.A., and Herzenberg, L.A. (1991). N-acetylcysteine inhibits latent HIV expression in chronically infected cells. AIDS Res. Hum. Retroviruses 7, 563-567
145. 145 Staal, F.J., Roederer, M., Herzenberg, L.A., and Herzenberg, L.A. (1990). Intracellular thiols regulate activation of nuclear factor kappa B and transcription of human immunodeficiency virus. Proc. Natl. Acad. Sci. USA 87, 9943-9947
146. 146 Roederer, M., Staal, F.J.T., Anderson, M.E., Rabin, R., Raju, P.A., Herzenberg, L.A., and Herzenberg, L.A. (1993). Disregulation of leukocyte glutathione in AIDS. Ann. NY Acad. Sci. 677, 113-125
147. 147 Herzenberg, L.A., De Rosa, S.C., Dubs, J.G., Roederer, M., Anderson, M.T., Ela, S.W., Deresinski, S.C., and Herzenberg, L.A. (1997). Glutathione deficiency is associated with impaired survival in HIV disease. Proc. Natl. Acad. Sci. USA 94, 1967-1972
148. 148 Baur, A., Harrer, T., Peukert, M., Jahn, G., Kalden, J.R., and Fleckenstein, B. (1991). Alpha-lipoic acid is an effective inhibitor of human immuno-deficiency virus (HIV-1) replication. Klin. Wochenschr. 69, 722-724
149. 149 Nabel, G. and Baltimore, D. (1987). An inducible transcription factor activates expression of human immunodeficiency virus in T cells [published erratum appears in Nature 1990 344(6262):178]. Nature 326, 711-713
150. 150 Nabel, G.J., Rice, S.A., Knipe, D.M., and Baltimore, D. (1988). Alternative mechanisms for activation of human immunodeficiency virus enhancer in T cells. Science 239, 1299-1302
151. 151 Roederer, M., Staal, F.J., Raju, P.A., Ela, S.W., Herzenberg, L.A., and Herzenberg, L.A. (1990). Cytokine-stimulated human immunodeficiency virus replication is inhibited by N-acetyl-L-cysteine. Proc. Natl. Acad. Sci. USA 87, 4884-4888
152. 152 Yan, C.H.I., Ferrari, G., and Greene, L.A. (1995). N-Acetylcysteine-promoted survival of PC12 cells is glutathione-independent but transcription-dependent. J. Biol. Chem. 270, 26827-26832
153. 153 Suzuki, Y.J. and Packer, L. (1994). Alpha-lipoic acid is a potent inhibitor of NF-kappa B activation in human T-cells: Does the mechanism involve antioxidant activities. In: Biological Oxidants and Antioxidants: New Strategies in Prevention and Therapy (L. Packer and E. Cadenas, eds.), Hippocrates Verlag, Stuttgart
154. 154 Suzuki, Y.J., Agarwal, B.B., and Packer, L. (1992). Alpha-lipoic acid is a potent inhibitor of NF-κB activation in human T cells. Biochem. Biophys. Res. Commun. 189, 1709-1715
155. 155 Suzuki, Y.J., Mizuno, M., Tritschler, H.J., and Packer, L. (1995). Redox regulation of NF-kappa B DNA binding activity by dihydrolipoate. Biochem. Mol. Biol. Int. 36, 241-246
156. 156 Kameoka, M., Okada, Y., Tobiume, M., Kimura, T., and Ikuta, K. (1996). Intracellular glutathione as a possible direct blocker of HIV type 1 reverse transcription. AIDS Res. Hum. Retroviruses 12, 1635-1638
157. 157 Sen, C.K., Roy, S., and Packer, L. (1996). Involvement of intracellular Ca2+ in oxidant-induced NF-kappa B activation. FEBS Lett. 385, 58-62
158. 158 Papp, B. and Byrn, R.A. (1995). Stimulation of HIV expression by intracellular calcium pump inhibition. J. Biol. Chem. 270, 10278-10283
159. 159 Droge, W., Eck, H.P., Naher, H., Pekar, U., and Daniel, V. (1988). Abnormal amino-acid concentrations in the blood of patients with acquired immunodeficiency syndrome (AIDS) may contribute to the immunological defect. Biol. Chem. Hoppe Seyler 369, 143-148
160. 160 Merin, J.P., Matsuyama, M., Kira, T., Baba, M., and Okamoto, T. (1996). Alpha-lipoic acid blocks HIV-1 LTR-dependent expression of hygromycin resistance in THP-1 stable transformants. FEBS Lett. 394, 9-13
161. 161 Bubl, R., Jaffe, H.A., Holroyd, K.J., Wells, F.B., Mastrangeli, A., Saltini, C., Cantin, A.M., and Crystal, R.G. (1989). Systemic glutathione deficiency in symptom-free HIV-seropositive individuals [see comments]. Lancet 2, 1294-1298
162. 162 Suarez, M., Beloqui, O., Ferrer, J.V., Fil, B., Qian, C., Garcia, N., Civeira, P., and Prieto, J. (1993). Glutathione depletion in chronic hepatitis C. Int. Hepatol. Commun. 1, 215-221
163. 163 Loguercio, C., Tarante, D., Vitale, L.M., Beneduce, F., and Del Vecchio Blanco, C. (1996). Effect of liver cirrhosis and age on the glutathione concentration in the plasma, erythrocytes, and gastric mucosa of man. Free Radic. Biol. Med. 20, 483-488
164. 164 Forrester, T.E., Badaloo, V., Bennett, F.I., and Jackson, A.A. (1990). Excessive excretion of 5-oxoproline and decreased levels of blood glutathione in type II diabetes mellitus. Eur. J. Clin. Nutr. 44, 847-850
165. 165 Vijayalingam, S., Parthiban, A., Shanmugasundaram, K.R., and Mohan, V. (1996). Abnormal antioxidant status in impaired glucose tolerance and non-insulin-dependent diabetes mellitus. Diabet. Med. 13, 715-719
166. 166 Fields, J.A., Keshavarzian, A., Eiznhamer, D., Frommel, T., Winship, D., and Holmes, E.W. (1994). Low levels of blood and colonie glutathione in ulcerative colitis. Gastroenterology 106, A680
167. 167 Martensson, J., Goodwin, C.W., and Blake, R. (1992). Mitochondrial glutathione in hypermetabolic rats following burn injury and thyroid hormone administration: Evidence of a selective effect on brain glutathione by burn injury. Metabolism 41, 273-277
168. 168 Sabeh, F., Baxter, C.R., and Norton, S.J. (1995). Skin burn injury and oxidative stress in liver and lung tissues of rabbit models. Eur. J. Clin. Chem. Clin. Biochem. 33, 323-328
169. 169 Cantin, A.M., Hubbard, R.C., and Crystal, R.G. (1989). Glutathione deficiency in the epithelial lining fluid of the lower respiratory tract in idiopathic pulmonary fibrosis. Am. Rev. Respir. Dis. 139, 370-372
170. 170 Pacht, E.R., Timerman, A.P., Lykens, M.G., and Merola, A.J. (1991). Deficiency of alveolar fluid glutathione in patients with sepsis and the adult respiratory distress syndrome. Chest 100, 1397-1403
171. 171 Verjee, Z.H. and Behal, R. (1976). Protein-calorie malnutrition: a study of red blood cell and serum enzymes during and after crisis. Clin. Chim. Acta. 70, 139-147
172. 172 Kondo, H. and Itokawa, Y. (1994). Oxidative stress in muscular atrophy. In: Exercise and oxygen toxicity (C.K. Sen, L. Packer, and O. Hanninen, eds.), pp. 319-342, Elsevier Science Publishers B.V., Amsterdam
173. 173 Nakata, K., Kawase, M., Ogino, S., Kinoshita, C., Murata, H., Sakaue, T., Ogata, K., and Ohmori, S. (1996). Effects of age on levels of cysteine, glutathione and related enzyme activities in livers of mice and rats and an attempt to replenish hepatic glutathione level of mouse with cysteine derivatives. Mech. Aging Dev. 90, 195-207
174. 174 de la Asuncion, J.G., Millan, A., Pla, R., Bruseghini, L., Esteras, A., Pallardo, F.V., Sastre, J., and Vina, J. (1996). Mitochondrial glutathione oxidation correlates with age-associated oxidative damage to mitochondrial DNA. Faseb J. 10, 333-338
175. 175 Hammarqvist, F., Luo, J.L., Cotgreave, I.A., Andersson, K., and Wernerman, J. (1997). Skeletal muscle glutathione is depleted in critically ill patients. Crit. Care Med. 25, 78-84
176. 176 Schmidt, H., Grune, T., Muller, R., Siems, W.G., and Wauer, R.R. (1996). Increased levels of lipid peroxidation products malondial-dehyde and 4-hydroxynonenal after perinatal hypoxia. Pediatr. Res. 40, 15-20
177. 177 Usai, A., Acarturk, E., Yuregir, G.T., Unlukurt, I., Demirci, C., Kurt, H.I., and Birand, A. (1996). Decreased glutathione levels in acute myocardial infarction. Jpn. Heart J. 37, 177-182
178. 178 Murphy, T.H., Miyamoto, M., Sastre, A., Schnaar, R.L., and Coyle, J.T. (1989). Glutamate toxicity in a neuronal cell line involves inhibition of cystine transport leading to oxidative stress. Neuron. 2, 1547-1558