Total Thiols: Biomedical Importance And Their Alteration In Various Disorders

Mungli, Prakash and Shetty, Mahesh S and Tilak, Prasiddha and Anwar, Naureen (2009) Total Thiols: Biomedical Importance And Their Alteration In Various Disorders. [Journal (On-line/Unpaginated)]

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Thiols are the organic compounds that contain a sulphydryl group. Among all the antioxidants that are available in the body, thiols constitute the major portion of the total body antioxidants and they play a significant role in defense against reactive oxygen species. Total thiols composed of both intracellular and extracellular thiols either in the free form as oxidized or reduced glutathione, or thiols bound to proteins. Among the thiols that are bound to proteins, albumin makes the major portion of the protein bound thiols, which binds to sufhydryl group at its cysteine-34 portion. Apart from their role in defense against free radicals, thiols share significant role in detoxification, signal transduction, apoptosis and various other functions at molecular level. The thiol status in the body can be assessed easily by determining the serum levels of thiols. Decreased levels of thiols has been noted in various medical disorders including chronic renal failure and other disorders related to kidney, cardiovascular disorders, stroke and other neurological disorders, diabetes mellitus, alcoholic cirrhosis and various other disorders. Therapy using thiols has been under investigation for certain disorders

Item Type:Journal (On-line/Unpaginated)
Keywords:Thiols, antioxidants, glutathione, free radicals, kidney diseases, cysteine-SH, γ-glutamyl cycle
Subjects:JOURNALS > Online Journal of Health and Allied Sciences
ID Code:6664
Deposited By: Kakkilaya Bevinje, Dr. Srinivas
Deposited On:14 Nov 2009 11:40
Last Modified:11 Mar 2011 08:57

References in Article

Select the SEEK icon to attempt to find the referenced article. If it does not appear to be in cogprints you will be forwarded to the paracite service. Poorly formated references will probably not work.

1. Rossi R, Giustarini D, Milzani A, Dalle-Donne I. Cysteinylation and homocysteinylation of plasma protein thiols during ageing of healthy humans. J Cell Mol Med 2008;10:1582-4934.

2. Giustarini D, Dalle-Donne I, Lorenzini S, et al. Age-related influence on thiol, disulphide and protein mixed disulphide levels in human plasma. J Gerontol A 2006;61:1030–8.

3. Mansoor MA, Svardal AM, Ueland PM. Determination of the in vivo redox status of cysteine, cysteinylglycine, homocysteine, and glutathione in human plasma. Anal Biochem 1992;200:218–29.

4. Dalle-Donne I, Milzani A, Gagliano N et al. Molecular mechanisms and potential clinical significance of S-glutathionylation. Antioxid Redox Signal 2008;10:446–73.

5. Jones DP, Carlson JL, Mody VC et al. Redox state of glutathione in human plasma. Free Radic Biol Med 2000;28:625–35.

6. Lumb RA, Bulleid NJ. Is protein disul®de isomerase a redox-dependent molecular chaperone? The EMBO Journal 2002;2:6763-70.

7. Curry S, Mandelkow H, Brick P et al. Crystal structure of human serum albumin complexed with fatty acid reveals an asymmetric distribution of binding sites. Nat Struct Biol 1998;5:827–35.

8. Prakash M, Upadhya S, Prabhu R. Protein thiol oxidation and lipid peroxidation in patients with uremia. Scand J Clin Lab Invest 2004;64:599-604.

9. Monod J, Wyman J, Changeux JP. On the nature of allosteric transitions: a plausible model. J Mol Biol 1965;12:88–118.

10. Peters T. All About Albumin: Biochemistry, Genetics, and Medical Applications. 1996; Academic Press, San Diego, CA: 51–54.

11. Carter DC, Ho JX. Structure of serum albumin. Adv Protein Chem. 1994;45:153–203.

12. Narazaki R, Hamada M, Harada K, Otagiri M. Covalent binding between bucillamine derivatives and human serum albumin. Pharm Res 1996;13:1317- 21.

13. DeLeve L, Kaplowitz N. Glutathione metabolism and its role in hepatotoxicity. Pharmaco Ther 1991;52:287–305.

14. Hwang C, Sinsky AJ, Lodish HF. Oxidized redox state of glutathione in the endoplasmic reticulum. Science 1992;257:1496–1502.

15. Meredith MJ, Reed DJ. Status of the mitochondrial pool of glutathione in the isolated hepatocyte. J Biol Chem 1982;257:3747–53.

16. Meister A. Glutathione. In: The Liver: Biology and Pathobiology, Aria IM, Jakoby WB, Popper H. et al., eds; 2nd edition, Raven Press, New York pp. 401–417.

17. Stamler JS, Slivka A. Biological chemistry of thiols in the vasculature and in vascular-related disease. Nutr Rev 1996;54:1–30.

18. Fortin LJ, Genest J Jr. Measurement of homocyst(e)ine in the prediction of arteriosclerosis. Clin Biochem 1995;28:155– 62.

19. Finkelstein JD. The metabolism of homocysteine: Pathways and regulation. Eur J Pediatr 1998;157 Suppl:S40–4.

20. Garcia´ de la Asuncio´n J, Olmo MLD et al. AZT treatment induces molecular and ultrastructural oxidative damage to muscle mitochondria. J Clin Invest 1998;102:4 –9.

21. Bannai S, Ishii T, Takada A, Noriko T. Regulation of glutathione level by amino acid transport. In: GlutathioneCentennial; Taniguchi N, Higashi T, Sakamoto Y, Meister A. eds,1989, Academic Press, San Diego, pp. 407–21.

22. Kilberg MS. Amino acid transport in isolated rat hepatocytes. J Membr Biol 1982;69:1–12.

23. Takada A, Bannai S. Transport of cystine in isolated rat hepatocytes in primary culture. J Biol Chem 1984:259:2441–5.

24. Ferna´ndez-Checa J, Lu SC, Ookhtens M, DeLeve L,Runnegar M et al. The Regulation of Hepatic Glutathione. In:Hepatic Anion Transport and Bile Secretion: Physiology and Pathophysiology, Tavoloni N, Berk PD, eds, Marcel Dekker, New York. 1992, pp. 363–95.

25. Meister A. Glutathione metabolism and its selective modification. J Biol Chem 1988;263:17205– 8.

26. Arrick BA, Nathan CF. Glutathione metabolism as a determinant of therapeutic efficacy. Cancer Res 1984;44:4224–32.

27. Ghibelli L, Coppola S, Rotilio G et al. Non-oxidative loss of glutathione in apoptosis via GSH extrusion. Biochem Biophys Res Commun 1995;216:313–20.

28. Van den Dobbelsteen DJ, Nobel CSI, Schlegel J et al. Rapid and specific efflux of reduced glutathione during apoptosis induced by anti-Fas/APO-1 antibody. J Biol Chem 1996;271:15420–7.

29. Kohno T, Yamada Y, Hata T, Mori H et al. Relation of oxidative stress and glutathione synthesis to CD95 (Fas/APO-1)-mediated apoptosis of adult T cell leukemia cells. J Immunol 1996;156:4722–8.

30. Delneste Y, Jeannin P, Sebille E et al. Thiols prevent Fas (CD95)-mediated T cell apoptosis by down-regulating membrane Fas expression. Eur J Immunol 1996;26:2981–8.

31. Cotgreave IA, Gerdes RC. Recent trends in glutathione biochemistry-glutathione-protein interactions: a molecular link between oxidative stress and cell proliferation? Biochem Biophys Res Commun 1998;242:1–9.

32. Mills BJ, Lang CA. Differential distribution of free and bound glutathione and cyst(e)ine in human blood. Biochem Pharmacol 1996;52:401–6.

33. Padgett CM, Whorton AR. Cellular responses to nitric oxide: role of protein S-thiolation/dethiolation. Arch Biochem Biophys 1998;358:232–42.

34. Essex DW, Li M. Redox control of platelet aggregation. Biochemistry 2003;42:129–136.

35. Matthias L J, Yam PT, Jiang XM et al. Disulfide exchange in domain 2 of CD4 is required for entry of HIV-1. Nat Immunol 2002;3:727-32.

36. Laragione T, Bonetto V, Casoni F et al. Redox regulation of surface protein thiols: Identification of integrin {alpha}-4 as a molecular target by using redox proteomics. Proc. Natl Acad Sci 2003;100:14737-41.

37. Jung CH, Thomas JA. S-glutathiolated hepatocyte proteins and insulin disulfides as substrates for reduction by glutaredoxin, thioredoxin, protein disulfide isomerase and glutathione. Arch Biochem Biophys 1996;335:61–72.

38. Qiao F, Xing K, Lou MF. Modulation of lens glycolytic pathway by thioltransferase. Exp Eye Res 2000;70:745–53.

39. Stocker R, Keaney JF. Role of oxidative modifications in atherosclerosis. Physiol Rev 2004;84:1381-478.

40. Giustarini D, Rossi R, Milzani A et al. S-Glutathionylation: from redox regulation of protein functions to human diseases. J Cell Mol Med 2004;8:201–12.

41. Barrett WC, DeGnore JP, Konig S et al. Regulation of PTP1B via glutathionylation of the active site cysteine 215. Biochemistry 1999;38:6699–705.

42. Davies MJ, Fu S, Wang H, Dean RT. Stable markers of oxidant damage to proteins and their application in study of human diseases. Free Radic Biol Med 1999;27:1151–61.

43. Himmelfarb J, McMonagle E, McMenamin E. Plasma protein thiol oxidation and carbonyl formation in chronic renal failure. Kidney Int 2000;57:2571-8.

44. Stamler JS, Lamas S, Fang FC. Nitrosylation: the prototypic redox-based signaling mechanism. Cell 2001;106:675– 83.

45. Foster MW, McMahon TJ, Stamler JS. S-nitrosylation in health and disease. Trends Mol Med 2003;9:160–8.

46. Liu L, Yan Y, Zeng M et al. Essential roles of S-nitrosothiols in vascular homeostasis and endotoxic shock. Cell 2004;116:617– 28.

47. Gandley RE, Tyruin VA, Huang W, Arroyo A. S-nitroso-albuminmediated relaxation is enhanced by ascorbate and copper: implications for impaired vascular function in preeclampsia. Hypertension 2005;45:21–7.

48. Stamler JS, Jaraki O, Osborne J et al. Nitric oxide circulates in mammalian plasma primarily as an S-nitroso adduct of serum albumin. Proc Natl Acad Sci. 1992;89:7674–7.

49. Nedospasov A, Rafikov R, Beda N, Nudler E. An autocatalytic mechanism of protein nitrosylation. Proc Natl Acad Sci 2000;97:13543–8.

50. Rafikova O, Rafikov R, Nudler E. Catalysis of S-nitrosothiols formation by serum albumin: The mechanism and implication in vascular control. Proc Natl Acad Sci 2002;99:5913–8.

51. Stubauer G, Giuffre A, Sarti P. Mechanism of S-nitrosothiol formation and degradation mediated by copper ions. J Biol Chem 1999;274:28128–33.

52. Raijmakers MR. Zusterzee MP, Steegers EP et al. Plasma Thiol Status in Preeclampsia. Obstet Gynecol 2000;95:180–4.

53. Patwari P, Lee RT. Thioredoxins, Mitochondria, and Hypertension. Am J Pathol 2007;170:805–8.

54. Heinecke JM, Kawamura L, Suzuki et al. Oxidation of low density lipoprotein by thiols: superoxide-dependent and independent mechanisms. J Lipid Res 1993;34:2051-61.

55. Galle J. Oxidative stress in Chronic Renal Failure. Nephrol Dial Transplant. 2001;16:2135-37.

56. Himmelfarb J, Hakim HR. Oxidative stress in uremia. Curr Opin Nephrol Hypertens 2003;12:593-94.

57. Shetty JK, Prakash M, Tripathy S et. al. Serum Paraoxonase activity and protein thiols in chronic renal failure patients. Asian J Biochem. 2007;2:274-8.

58. Himmelfarb J, Mcmonagle E, Freedman S et al. Oxidative stress is increased in critically ill patients with acute renal failure. J Am Soc Nephrol 2004;15:2449-56.

59. Mallikarjunappa S, Prakash M. Urine protein thiols in chronic renal failure patients. Indian J Nephrol 2007;17:7-9.

60. Prakash M, Shetty JK, Awanti SM et al. Urinary protein thiols in different grades of proteinuria. Ind J Clin Biochem 2008;23:404-6.

61. Karthikeyan K, Sinha I, Prabhu K et al. Plasma protein thiols and total antioxidant power in paediatric nephrotic syndrome. Nephron Clin Pract 2008;110:10-4.

62. Markan S, Kohli HS, Sud K et al. Oxidative stress in primary glomerular diseases: a comparative study. Mol Cell Biochem 2008;311:105-10.

63. Oberg BP, Elizabeth, Mcmenamin et al. Increased prevelance of oxidative stress and inflammation in patients with moderate to severe chronic kidney disease. Kidney int 2004;65:1009-16.

64. Palleschi S, De Angells S, Rossi B et al. Homocysteinemia correlates with plasma thiol redox status in patients with end stage renal disease. Nephron Clin Prac 2008;108:106-12.

65. Morgan PE, Sturgess AD, Hennessy A, Davies MJ. Serum protein oxidation and apolipoprotein CIII levels in people with systemic lupus erythematous with and without nephritis. Free Rad Res 2007;41:1301-12

66. Gallardo JM, De Carmen Prado-Uribe M, Amato D, Paniagua R. Inflammation and oxidative stress markers by pentoxifylline treatment in rats with chronic renal failure and high sodium intake. Arch Med Res 2007;38:34-8.

67. Prakash M, Shetty JK, Tripathy S et al. Serum total thiols status in alcohol abusers. Asian J Biochem 2008;3:48-51.

68. Venkatraman A, Lander A , Ashley JD et al. Oxidative modification of hepatic mitochondria protein thiols, effects of chronic alchohol consumption. Am J Physiol Gastrointest Liver Physiol 2004;286:G521-7.

69. Peters WH, Van Schaik A, Peters JH, Van Goor H. Oxidized and total non- protein bound glutathione and related thiols in gallbladder bile of patients with various gastrointestinal disorders. BMC Gastroenterol 2007;7:7.

70. Ookhtens M, Kaplowitz N. Role of the liver in interorgan homeostasis of glutathione and cyst(e)ine. Semin Liver Dis 1998;18:313-29.

71. Yilmaz IA, Akçay T, Cakatay U et al. Relation between bladder cancer and protein oxidation. Int Urol Nephrol 2003;35:345-50.

72. Aslan M, Nazligul Y, Horoz M et al. Serum paraoxonase -1 activity in Helicobacter pylori infected subjects. Atherosclerosis 2008;196:270-4.

73. Dorge W. Free radicals in the physiological control of cell function. Physiol Rev 2002;82:47–95.

74. Ann VC, Christel VC, Albert RL et al. Impact of diabetes mellitus on the relationships between iron-, inflammatory-and oxidative stress status. Diabetes/metabolism research and reviews 2006;22:444-54.

75. Srivatsan R, Das S, Gadde R et al. Antioxidants and lipid peroxidation status in diabetic patients with and without complications. Arch Iran Med 2009;12: 121–7.

76. Pasaoglu H, Sancak B, Burkan N. Lipid peroxidation and resistance to oxidation in patients with type 2 diabetes mellitus. Tohuku J Exp Med 2004;203:211–8.

77. Dursun E, Timur M, Dursun B, et al. Protein oxidation in Type 2 diabetic patients on hemodialysis. J Diabetes Complications 2005;19:142-6.

78. Shetty JK, Prakash M, Ibrahim SM. Relationship between free iron and glycated hemoglobin in uncontrolled type 2 diabetes patients associated with complications. Ind J Biochem 2008;23:67-70.

79. Zeng J, Davies MJ. Protein and low molecular mass thiols as targets and inhibitors of glycation reactions. Chem Res Toxicol 2006;19:1668–76

80. Kamath U, Guruprasad R, Raghothama C et al. Erythrocyte indicators of oxidative stress in gestational diabetes. Acta Paediatr 1998;87:676–9.

81. Bis-Gluchowska, Marciniak B, Szpringer-Bogun E et al. Determination of antioxidative-peroxidative balance in the cord blood of newborns delivered to mother with diabetes type G1. Ginekol Pol 2001;72:1255–8.

82. Nasrat H, Fageeh W, Abalkhail B et al. Determinants of pregnancy in patients with gestational diabetes. Int Gynaecol Obstet 1996;53:117–23.

83. Xinhua O Chen Md, Scholl TO. Oxidative stress: Changes in pregnancy and with gestational diabetes mellitus. Current Diabetes Reports 2005;5: 282–8.

84. Dey P, Gupta P, Acharya NK et, al. Antioxidants and lipid peroxidation in gestational diabetes- a preliminary study. Indian J Physiol Pharmacol 2008;52:149–56.

85. Konarkowska1 B, Aitken J, Kistler J et al. Thiol reducing compounds prevent human amylin-evoked cytotoxicity. FEBS J 2005;272:4949–59.

86. Prabhu K, Kumar P, Pai M et al. A preliminary study of protein thiols and serum choline esterase in assisted reproduction. Ind J Clin Biochem 2008;23:98-99.

87. Jagatha B, Mythri RB, Vali S et al. Curcumin treatment alleviates the effects of glutathione depletion in vitro and in vivo: therapeutic implications for parkinson’s disease explained in silico studies. Free Radic Biol Med 2008;44:907-17.

88. Deitrich MA, Olas B, Glowackik, Bald E. Oxidative /nitrative modifications of plasma proteins and thiols from patients with schizophrenia. Neuropsychobiology 2009;59:1-7.

89. Fendri C, Mechri A, Khiari G et al. Oxidative stress involvement in schizophrenia. Encephale 2006;32:244-52.

90. Karunakaran S , Diwakar L, Saeed U et al. Activation of apoptosis signal regulating kinase 1 ( ASK1) and translocation of death associated proteins, Daxx, in substantia nigra pars compacta in a mouse model of Parkinson’s disease: protection by alpha- lipoic acid. FASEB J 2007;21:2226-36.

91. Soran N, Altindag O, Cakir H et al. Assessment of paraoxonase activities in patients with knee osteoarthritis. Redox Rep 2008;13:194-8.

92. Firuzi O, Spadaro A, Spadaro C et al. Protein oxidation markers in serum and synovial fluid of psoriatic arthritis patients. J Clin Lab Anal 2008;22:210-5.

93. Harma M, Harma M, Kocyigit A. Comparison of protein carbonyl and total plasma thiol concentrations in patients with complete hydatidiform mole with those in healthy pregnant women. Acta Obstet Gynecol Scand 2004;83:857-60.

94. Ece A, Kelekçi S, Hekimoğlu A et al. Neutrophil activation, protein oxidation and ceruloplasmin levels with Henoch- Schönlein purpura. Pediatr Nephrol 2007;22:1151-7.

95. Yazici C, Köse K, Calis M et al. Protein oxidation status in patients with ankylosing spondylitis. Rheumatology 2004;43:1235-9.

96. Samuele A, Mangiagalli A, Armentero MT et al. Oxidative stress and pro-apoptotic conditions in a rodent model of Wilson’s disease. Biochim Biophys Acta 2005;1741:325-30


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