BCL-2 expression or antioxidants prevent hyperglycemia-induced formation of intracellular advanced glycation endproducts in bovine endothelial cells. (original) (raw)
- Journal List
- J Clin Invest
- v.97(6); 1996 Mar 15
- PMC507201
J Clin Invest. 1996 Mar 15; 97(6): 1422–1428.
Department of Medicine, Albert Einstein College of Medicine, New York, USA.
Abstract
Hyperglycemia rapidly induces an increase in intracellular advanced glycation end products (AGEs) in bovine endothelial cells, causing an alteration in bFGF activity (Giardino, I., D. Edelstein, and M. Brownlee. 1994. J. Clin. Invest. 94:110-117). Because sugar or sugar-adduct autoxidation is critical for AGE formation in vitro, we evaluated the role of reactive oxygen species (ROS) in intracellular AGE formation, using bovine aortic endothelial cells. 30 mM glucose increased intracellular ROS formation by 250% and lipid peroxidation by 330%, while not affecting ROS in the media. In cells depleted of glutathione, intracellular AGE accumulation increased linearly with ROS generation as measured by immunoblotting and the fluorescent probe DCFH (AGE 0.258-3.531 AU* mm/5x10(4) cells, DCF 57-149 mean AU, r = .998, P < .002). Deferoxamine, alpha-tocopherol, and dimethylsulfoxide each inhibited hyperglycemia-induced formation of both ROS and AGE. To differentiate an effect of ROS generation on AGE formation from an effect of more distal oxidative processes, GM7373 endothelial cell lines were generated that stably expressed the peroxidation-suppressing proto-oncogene bcl-2. bcl-2 had no effect on hyperglycemia-induced intracellular ROS formation. In contrast, bcl-2 expression decreased both lipid peroxidation (100% at 3 h and 29% at 168 h) and AGE formation (55% at 168 h). These data show that a ROS-dependent process plays a central role in the generation of intracellular AGEs, and that inhibition of oxidant pathways prevents intracellular AGE formation.
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- Kuusisto J, Mykkänen L, Pyörälä K, Laakso M. NIDDM and its metabolic control predict coronary heart disease in elderly subjects. Diabetes. 1994 Aug;43(8):960–967. [PubMed] [Google Scholar]
- Kinoshita JH. A thirty year journey in the polyol pathway. Exp Eye Res. 1990 Jun;50(6):567–573. [PubMed] [Google Scholar]
- Derubertis FR, Craven PA. Activation of protein kinase C in glomerular cells in diabetes. Mechanisms and potential links to the pathogenesis of diabetic glomerulopathy. Diabetes. 1994 Jan;43(1):1–8. [PubMed] [Google Scholar]
- King GL, Shiba T, Oliver J, Inoguchi T, Bursell SE. Cellular and molecular abnormalities in the vascular endothelium of diabetes mellitus. Annu Rev Med. 1994;45:179–188. [PubMed] [Google Scholar]
- Williamson JR, Chang K, Frangos M, Hasan KS, Ido Y, Kawamura T, Nyengaard JR, van den Enden M, Kilo C, Tilton RG. Hyperglycemic pseudohypoxia and diabetic complications. Diabetes. 1993 Jun;42(6):801–813. [PubMed] [Google Scholar]
- Bucala R, Makita Z, Koschinsky T, Cerami A, Vlassara H. Lipid advanced glycosylation: pathway for lipid oxidation in vivo. Proc Natl Acad Sci U S A. 1993 Jul 15;90(14):6434–6438. [PMC free article] [PubMed] [Google Scholar]
- Vlassara H, Bucala R, Striker L. Pathogenic effects of advanced glycosylation: biochemical, biologic, and clinical implications for diabetes and aging. Lab Invest. 1994 Feb;70(2):138–151. [PubMed] [Google Scholar]
- Brownlee M, Cerami A, Vlassara H. Advanced glycosylation end products in tissue and the biochemical basis of diabetic complications. N Engl J Med. 1988 May 19;318(20):1315–1321. [PubMed] [Google Scholar]
- Makita Z, Vlassara H, Rayfield E, Cartwright K, Friedman E, Rodby R, Cerami A, Bucala R. Hemoglobin-AGE: a circulating marker of advanced glycosylation. Science. 1992 Oct 23;258(5082):651–653. [PubMed] [Google Scholar]
- Giardino I, Edelstein D, Brownlee M. Nonenzymatic glycosylation in vitro and in bovine endothelial cells alters basic fibroblast growth factor activity. A model for intracellular glycosylation in diabetes. J Clin Invest. 1994 Jul;94(1):110–117. [PMC free article] [PubMed] [Google Scholar]
- Fu MX, Wells-Knecht KJ, Blackledge JA, Lyons TJ, Thorpe SR, Baynes JW. Glycation, glycoxidation, and cross-linking of collagen by glucose. Kinetics, mechanisms, and inhibition of late stages of the Maillard reaction. Diabetes. 1994 May;43(5):676–683. [PubMed] [Google Scholar]
- Presta M, Maier JA, Rusnati M, Ragnotti G. Basic fibroblast growth factor is released from endothelial extracellular matrix in a biologically active form. J Cell Physiol. 1989 Jul;140(1):68–74. [PubMed] [Google Scholar]
- Boissy RE, Trinkle LS, Nordlund JJ. Separation of pigmented and albino melanocytes and the concomitant evaluation of endogenous peroxide content using flow cytometry. Cytometry. 1989 Nov;10(6):779–787. [PubMed] [Google Scholar]
- Hensley K, Carney JM, Mattson MP, Aksenova M, Harris M, Wu JF, Floyd RA, Butterfield DA. A model for beta-amyloid aggregation and neurotoxicity based on free radical generation by the peptide: relevance to Alzheimer disease. Proc Natl Acad Sci U S A. 1994 Apr 12;91(8):3270–3274. [PMC free article] [PubMed] [Google Scholar]
- Dennery PA, Kramer CM, Alpert SE. Effect of fatty acid profiles on the susceptibility of cultured rabbit tracheal epithelial cells to hyperoxic injury. Am J Respir Cell Mol Biol. 1990 Aug;3(2):137–144. [PubMed] [Google Scholar]
- Bischoff J, Lodish HF. Two asialoglycoprotein receptor polypeptides in human hepatoma cells. J Biol Chem. 1987 Aug 25;262(24):11825–11832. [PubMed] [Google Scholar]
- Horiuchi S, Araki N, Morino Y. Immunochemical approach to characterize advanced glycation end products of the Maillard reaction. Evidence for the presence of a common structure. J Biol Chem. 1991 Apr 25;266(12):7329–7332. [PubMed] [Google Scholar]
- Laemmli UK. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. [PubMed] [Google Scholar]
- Araki N, Ueno N, Chakrabarti B, Morino Y, Horiuchi S. Immunochemical evidence for the presence of advanced glycation end products in human lens proteins and its positive correlation with aging. J Biol Chem. 1992 May 25;267(15):10211–10214. [PubMed] [Google Scholar]
- Gebicki JM, Hicks M. Preparation and properties of vesicles enclosed by fatty acid membranes. Chem Phys Lipids. 1976 Mar;16(2):142–160. [PubMed] [Google Scholar]
- Hunt JV, Simpson JA, Dean RT. Hydroperoxide-mediated fragmentation of proteins. Biochem J. 1988 Feb 15;250(1):87–93. [PMC free article] [PubMed] [Google Scholar]
- Palinski W, Ylä-Herttuala S, Rosenfeld ME, Butler SW, Socher SA, Parthasarathy S, Curtiss LK, Witztum JL. Antisera and monoclonal antibodies specific for epitopes generated during oxidative modification of low density lipoprotein. Arteriosclerosis. 1990 May-Jun;10(3):325–335. [PubMed] [Google Scholar]
- Starr RG, Lu B, Federoff HJ. Functional characterization of the rat GAP-43 promoter. Brain Res. 1994 Feb 28;638(1-2):211–220. [PubMed] [Google Scholar]
- Geller AI, Freese A. Infection of cultured central nervous system neurons with a defective herpes simplex virus 1 vector results in stable expression of Escherichia coli beta-galactosidase. Proc Natl Acad Sci U S A. 1990 Feb;87(3):1149–1153. [PMC free article] [PubMed] [Google Scholar]
- Federoff HJ, Geschwind MD, Geller AI, Kessler JA. Expression of nerve growth factor in vivo from a defective herpes simplex virus 1 vector prevents effects of axotomy on sympathetic ganglia. Proc Natl Acad Sci U S A. 1992 Mar 1;89(5):1636–1640. [PMC free article] [PubMed] [Google Scholar]
- Bergold PJ, Casaccia-Bonnefil P, Zeng XL, Federoff HJ. Transsynaptic neuronal loss induced in hippocampal slice cultures by a herpes simplex virus vector expressing the GluR6 subunit of the kainate receptor. Proc Natl Acad Sci U S A. 1993 Jul 1;90(13):6165–6169. [PMC free article] [PubMed] [Google Scholar]
- Wolff SP, Dean RT. Glucose autoxidation and protein modification. The potential role of 'autoxidative glycosylation' in diabetes. Biochem J. 1987 Jul 1;245(1):243–250. [PMC free article] [PubMed] [Google Scholar]
- Hunt JV, Dean RT, Wolff SP. Hydroxyl radical production and autoxidative glycosylation. Glucose autoxidation as the cause of protein damage in the experimental glycation model of diabetes mellitus and ageing. Biochem J. 1988 Nov 15;256(1):205–212. [PMC free article] [PubMed] [Google Scholar]
- Ku RH, Billings RE. The role of mitochondrial glutathione and cellular protein sulfhydryls in formaldehyde toxicity in glutathione-depleted rat hepatocytes. Arch Biochem Biophys. 1986 May 15;247(1):183–189. [PubMed] [Google Scholar]
- Palinski W, Koschinsky T, Butler SW, Miller E, Vlassara H, Cerami A, Witztum JL. Immunological evidence for the presence of advanced glycosylation end products in atherosclerotic lesions of euglycemic rabbits. Arterioscler Thromb Vasc Biol. 1995 May;15(5):571–582. [PubMed] [Google Scholar]
- Hockenbery DM, Oltvai ZN, Yin XM, Milliman CL, Korsmeyer SJ. Bcl-2 functions in an antioxidant pathway to prevent apoptosis. Cell. 1993 Oct 22;75(2):241–251. [PubMed] [Google Scholar]
- Malhotra OP, Srivastava DK, Kayastha AM, Srinivasan Inactivation of glyceraldehyde-3-phosphate dehydrogenase with SH-reagents and its relationship to the protein quaternary structure. Indian J Biochem Biophys. 1993 Oct;30(5):264–269. [PubMed] [Google Scholar]
- Shivakumar BR, Ravindranath V. Selective modulation of glutathione in mouse brain regions and its effect on acrylamide-induced neurotoxicity. Biochem Pharmacol. 1992 Jan 22;43(2):263–269. [PubMed] [Google Scholar]
- Mullarkey CJ, Edelstein D, Brownlee M. Free radical generation by early glycation products: a mechanism for accelerated atherogenesis in diabetes. Biochem Biophys Res Commun. 1990 Dec 31;173(3):932–939. [PubMed] [Google Scholar]
- Sakurai T, Sugioka K, Nakano M. O2- generation and lipid peroxidation during the oxidation of a glycated polypeptide, glycated polylysine, in the presence of iron-ADP. Biochim Biophys Acta. 1990 Mar 12;1043(1):27–33. [PubMed] [Google Scholar]
- Jiang ZY, Woollard AC, Wolff SP. Hydrogen peroxide production during experimental protein glycation. FEBS Lett. 1990 Jul 30;268(1):69–71. [PubMed] [Google Scholar]
- Hunt JV, Bottoms MA, Mitchinson MJ. Oxidative alterations in the experimental glycation model of diabetes mellitus are due to protein-glucose adduct oxidation. Some fundamental differences in proposed mechanisms of glucose oxidation and oxidant production. Biochem J. 1993 Apr 15;291(Pt 2):529–535. [PMC free article] [PubMed] [Google Scholar]
- Wells-Knecht KJ, Zyzak DV, Litchfield JE, Thorpe SR, Baynes JW. Mechanism of autoxidative glycosylation: identification of glyoxal and arabinose as intermediates in the autoxidative modification of proteins by glucose. Biochemistry. 1995 Mar 21;34(11):3702–3709. [PubMed] [Google Scholar]
- Szwergold BS, Kappler F, Brown TR. Identification of fructose 3-phosphate in the lens of diabetic rats. Science. 1990 Jan 26;247(4941):451–454. [PubMed] [Google Scholar]
- Franzini E, Sellak H, Hakim J, Pasquier C. Comparative sugar degradation by (OH). produced by the iron-driven Fenton reaction and gamma radiolysis. Arch Biochem Biophys. 1994 Mar;309(2):261–265. [PubMed] [Google Scholar]
- Gutteridge JM. Thiobarbituric acid-reactivity following iron-dependent free-radical damage to amino acids and carbohydrates. FEBS Lett. 1981 Jun 15;128(2):343–346. [PubMed] [Google Scholar]
- Halliwell B, Gutteridge JM. Formation of thiobarbituric-acid-reactive substance from deoxyribose in the presence of iron salts: the role of superoxide and hydroxyl radicals. FEBS Lett. 1981 Jun 15;128(2):347–352. [PubMed] [Google Scholar]
- Gutteridge JM. Reactivity of hydroxyl and hydroxyl-like radicals discriminated by release of thiobarbituric acid-reactive material from deoxy sugars, nucleosides and benzoate. Biochem J. 1984 Dec 15;224(3):761–767. [PMC free article] [PubMed] [Google Scholar]
- Hammes HP, Strödter D, Weiss A, Bretzel RG, Federlin K, Brownlee M. Secondary intervention with aminoguanidine retards the progression of diabetic retinopathy in the rat model. Diabetologia. 1995 Jun;38(6):656–660. [PubMed] [Google Scholar]
- Brownlee M. Advanced protein glycosylation in diabetes and aging. Annu Rev Med. 1995;46:223–234. [PubMed] [Google Scholar]
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