Sod and GSH Inhibit the High Glucose-Induced Oxidative Damage and the PDGF Increased Secretion in Cultured Human Endothelial Cells

Summary

Poor control of blood glucose has been established as a key pathogenetic mechanism in the vascular complications of diabetes. It has been reported that glucose may autooxidize generating free radicals which have been suggested to delay proliferation, to modify mobility, to influence platelet-derived growth factor and other secretory protein production in a variety of cell systems. Platelet-derived growth factor, in turn, may induce proliferation and migration of vascular smooth muscle cells and thus play a role in atherogenesis. In the present study the effects of antioxidants on the high glucose-dependent oxidative cell damage and increased platelet-derived growth factor secretion have been investigated using cultured human endothelial cells. Our findings show that rising the glucose concentration in the culture medium from 5 mM to 20 mM, increased the production of free radicals cell damage markers, such as malondialdehyde and conjugated dienes, as well as the production of platelet-derived growth factor. The addition of superoxide dismutase or glutathione prevents both such effects. These results suggest that antioxidants may be a helpful therapeutic adjuvant to reduce the vascular complications of diabetes.

• References

• 1 Lorenzi M, Cagliero E, Toledo S. Glucose toxicity for human endothelial cells in culture. Delayed replication, disturbed cell cycle, and accelerated death Diabetes 1985; 34: 621-627
• 2 Lorenzi M, Nordberg JA, Toledo S. High glucose prolongs cell-cycle traversal of cultured human endothelial cells. Diabetes 1987; 36: 1261-1267
• 3 Boeri D, Almus FE, Maiello M, Cagliero E, Mohan Rao LV, Lorenzi M. Modification of tissue-factor mRNA and protein response to thrombin and interleukin-1 by high glucose in cultured human endothelial cells. Diabetes 1989; 38: 212-218
• 4 Roy S, Sala R, Cagliero E, Lorenzi M. Overexpression of fibronectin induced by diabetes or high glucose: phenomenon with a memory. Proc Natl Acad Sci USA 1990; 87: 404-408
• 5 Cagliero E, Roth T, Roy S, Lorenzi M. Characteristics and mechanisms of high-glucose-induced overexpression of basement membrane components in cultured human endothelial cells. Diabetes 1991; 40: 102-110
• 6 Wolf G, Sharma K, Chen Y, Ericksen M, Ziyadeh FN. High glucose-induced proliferation in mesangial cells is reversed by autocrine TGF-beta. Kidney Int 1992; 42: 647-656
• 7 Rocco MV, Chen Y, Goldfarb S, Ziyadeh FN. Elevated glucose stimulates TGF-beta gene expression and bioactivity in proximal tubule. Kidney Int 1992; 41: 107-114
• 8 Ziyadeh FN, Cohen MP. Effects of glycated albumin on mesangial cells: evidence for a role in diabetic nephropathy. Mol Cell Biochem 1993; 125: 19-25
• 9 Ziyadeh FN. Renal tubular basement membrane and collagen type IV in diabetes mellitus. Kidney Int 1993; 43: 114-120
• 10 Kunisaki M, Umeda F, Yamauchi T, Masakado M, Nawata H. High glucose reduces specific binding for D-alpha-tocopherol in cultured aortic endothelial cells. Diabetes 1993; 42: 1138-1146
• 11 Cohen MP, Ziyadeh FN. Amadori glucose adducts modulate mesangial cell growth and collagen gene expression. Kidney Int 1994; 45: 475-484
• 12 Ziyadeh FN, Sharma K, Ericksen M, Wolf G. Stimulation of collagen gene expression and protein synthesis in murine mesangial cells by high glucose is mediated by autocrine activation of transforming growth factor-beta. J Clin Invest 1994; 93: 536-542
• 13 Kannan K, Jain SH. Effect of high glucose on cellular proliferation and lipid peroxidation in cultured vero cells. Horm Metab Res 1994; 26: 322-325
• 14 Bleyer AJ, Fumo P, Snipes ER, Goldfarb S, Simmons DA, Ziyadeh FN. Polyol pathway mediates high glucose-induced collagen synthesis in proximal tubule. Kidney Int 1994; 45: 659-666
• 15 Fumo P, Kuncio GS, Ziyadeh FN. PKC and high glucose stimulate collagen alpha 1 (IV) transcriptional activity in a reporter mesangial cell line. Am J Physiol 1994; 267: 632-638
• 16 Wolff SP, Dean RT. Glucose autoxidation and protein modification. The potential role of “autoxidative” glycosilation in diabetes Biochem J 1987; 245: 243-250
• 17 Hunt JV, Dean R, Wolff SP. Hydroxyl radical production and autoxidative glycosilation. Glucose autoxidation as the cause of protein damage in the experimental glycation model of diabetes mellitus and ageing Biochem J 1988; 256: 205-212
• 18 Curcio F, Ceriello A. Decreased cultured endothelial cell proliferation in high glucose medium is reversed by antioxidants: new insights on the pathophysiological mechanisms of diabetic vascular complications. In Vitro Cell Dev Biol 1992; 28: 787-790
• 19 Le CT, Hollaar L, van der Valk EJ, van der Laarse A. Effects of glucose, Trolox-C, and glutathione disulphide on lipid peroxidation and cell death induced by oxidant stress in rat heart. Cardiovasc Res 1992; 26: 133-142
• 20 Nalini S, Ibrahim SA, Balasubramanian KA. Effect of oxidant exposure on monkey intestinal brush-border membrane. Biochim Biophys Acta 1993; 1147: 169-176
• 21 Trachtman H, Futterweit S, Bienkowski RS. Traurine prevents glucose-induced lipid peroxidation and increased collagen production in cultured rat mesangial cells. Biochem Biophys Res Commun 1993; 191: 759-765
• 22 Wolff SP. Diabetes mellitus and free radicals. Free radicals, transition metals and oxidative stress in the aetiology of diabetes mellitus and complications Br Med Bull 1993; 49: 642-652
• 23 Windsor DP, White IG, Selley ML, Swan MA. Effects of the lipid peroxidation product (E)-4-hydroxy-2-nonenal on ram sperm function. J Reprod Fertil 1993; 99: 359-366
• 24 Trachtman H. Vitamin E prevents glucose-induced lipid peroxidation and increased collagen production in cultured rat mesangial cells. Microvas Res 1994; 47: 232-239
• 25 Kawamura M, Heinecke JW, Chait A. Pathophysiological concentrations of glucose promote oxidative modification of low density lipoprotein by a superoxide-dependent pathway. J Clin Invest 1994; 94: 771-778
• 26 Umeda F, Yamauchi T, Nakashima N, Ono H, Nawata H, Masuko M, Nakayama K, Tatematsu A. Glucose reduces PDGF production and cell proliferation of cultured vascular endothelial cells. Horm Metab Res 1991; 23: 274-277
• 27 Mizutani M, Okuda Y, Yamaoka T, Tsukahara K, Isaka M, Bannai C, Yamashita K. High glucose and hyperosmolarity increase platelet-derived growth factor mRNA levels in cultured human vascular endothelial cells. Biochem Biophys Res Commun 1992; 187: 664-669
• 28 Montisano D, Mann T, Spragg RG. H₂O₂increases expression of pulmonary artery endothelial cell platelet derived growth factor mRNA. J Appl Physiol 1992; 73: 2255-2259
• 29 Ross R, Bowen-Pope DF. Raines EW Platelet-derived growth factor and its role in health and disease. Philos Trans R Soc 1990; 327: 155-169
• 30 Ross R, Masuda J, Raines E, Gown A, Katsuda S, Sasahara M, Malden L, Masuko H, Sato H. Localization of PDGF-B protein in macrophages in all phases of atherogenesis. Science 1990; 248: 1009-1012
• 31 foon HG. Uonal stability and phenotypic expression of chick emulate cells in vitro. Proc Nall Acad Sci USA 1966; 55: 66-67
• 32 Hinton K. A study of the conditions and mechanism of the diphenylamine reaction for colorimetric cxtimalion of deoxiribonudeic acid. Biochem J 1965; 62: 315-322
• 33 Bird RP, Draper HH. Comparative studies on methods of malondialdehyde determination. Methods in Enzymology. Vol 105 Colowick SP, Kaplan OP. eds New York: NY: Academic Press; 1984: 299-309
• 34 Massey KD, Burton KP. Free radical damage in neonatal rat cardiac myocyte cultures: effects of alpha-tocopherol, Trolox, and phylol. Free Radic Biol Med 1990; 8: 449-458
• 35 Wayne WD. Biostatistics: a foundation for analysis in the health sciences. III ed New York, NY: John Wiley & Sons; 1983: 230-237
• 36 Birinyi UK, Warner SJ, Salomon RN, Callow AD, Libby PJ. Observation on human smooth muscle cells cultures from hyperplastic lesions of prosthetic bypass grafts: production of a platelet-derived growth factor-like mitogen and expression of a gene for a platelet-derived growth factor receptor-a preliminary study. Vase Surg 1989; 10: 157-165
• 37 Libby P, Salomon RN, Payne DD, Schoen L-J, Pober JS. functions of vascular wall cells related to the development of transplantation-associated coronary arteriosclerosis. Transplant Proc 1989; 21: 3677-3684
• 38 Raines EW, Dower SK, Ross R. Interleukin-1 mitogenic activity for fibroblasts and smooth muscle cells is due to PDGE-AA. Science 1989; 243: 393-396
• 39 Battegay EJ, Raines E, Seifert RA, Bowen-pope DE, Ross R. TGF-beta induces bitnodal proliferation of connective tissue cells via complex control of an autocrine PIXiE loop. cell 1990; 63: 515-524
• 40 Owens OK, Rabinovitch PS, Schwartz SM. Smooth muscle cells hypertrophy versus hyperplasia in hypertension. Proc Natl Acad Sci USA 1981; 78: 7759-7763
• 41 Barrett TB, Benditl EP. Platelet-derived growth factor gene expression in human atherosclerotic plaques and normal artery wall. Proc Natl Acad Sci USA 1988; 85: 2810-2814
• 42 Oberley LW. Free radicals and diabetes. Free Rad Biol Med 1988; 5: 113-124
• 43 Sato Y, llolta N, Sakamoto N, Malsuoka S, Ohishi N, Yagi K. Lipid peroxide levels in serum of diabetic patients. Biochem Med 1979; 21: 104-107
• 44 Ceriello A, Giugliano D, Quatraro A, Dello Russo P, Lefebvrc PJ. Metabolic control may influence the increased superoxide generation in diabetic serum. Diab Med 1991; 8: 540-542
• 45 Borg LA M, Eriksson V. I. Protection by free radical scavenging enzymes against glucose-induced embryonic malformations in vitro. Diabetologia 1991; 34: 325-331