Abstract
The present study was aimed at addressing the effect of hyperglycemia on antioxidant enzymes. The expression of catalase, superoxide dismutase and glutathione peroxidase, the three primary scavenger enzymes involved in detoxifying reactive oxygen species has been evaluated in the renal cortex of rats after 6 weeks of streptozotocin-induced diabetes. Lipid peroxidation and protein oxidation in the renal cortical homogenate were first performed to confirm a state of oxidative stress. The enzyme assays showed significant and varied alterations in catalase, superoxide dismutase and glutathione peroxidase activities. An opposing response of catalase and glutathione peroxidase activities to diabetes was observed. RT-PCR analysis was used to ascertain whether steady-state transcription levels were altered. While an increase in glutathione peroxidase and Cu-Zn superoxide dismutase mRNA parallels the increase in the activities of the enzymes, an increase in catalase gene expression in contrast to a decrease in enzyme activity suggests a role for post-translational modification in altering the activity of this enzyme.
Similar content being viewed by others
References
Braunlich H, Marx F, Stein G: Glutathione status, lipid peroxidation and kidney function in streptozotocin diabetic rats. Exp Toxicol Pathol 46: 143-147, 1994
Kakkar R, Mantha SV, Radhi J, Prasad K, Kalra J: Antioxidant defense system in diabetic kidney: A time course study. Life Sci 60: 667-679, 1997
MatÉs JM, Pérez-Gómez C, DeCastro IN: Antioxidant enzymes and human diseases. Clin Biochem 32: 595-603, 1999
Baynes JW, Thorpe SR: The role of oxidative stress in diabetic complications. Curr Opin Endocrinol 3: 277-284, 1996
Halliwell B, Gutteridge JMC: Free Radicals in Biology and Medicine. Clarendon Press, Oxford, 1999
Wohaieh SA, Godin DV: Alterations in free radical tissue-defense mechanisms in streptozocin-induced diabetes in rat. Effect of insulin treatment. Diabetes 36: 1014-1018, 1987
Kakkar R, Mantha SV, Radhi J, Prasad K, Kalra J: Lipid peroxidation and activity of antioxidant enzymes in diabetic rats. Mol Cell Biochem 151: 113-119, 1995
McDermott BM, Flatt PR, Strain JJ: Effects of copper deficiency and experimental diabetes on tissue antioxidant enzyme levels in rats. Ann Nutr Metab 38: 263-269, 1994
Godin DV, Wohaieh SA, Garnett ME, Goumeniouk AD: Antioxidant enzyme alterations in experimental and clinical diabetes. Mol Cell Biochem 84: 223-231, 1988
Duncan HF, Ip MSP, Li PC, Poon MKT, Ko KM: Alterations in tissue glutathione antioxidant system in streptozotocin-induced diabetic rats. Mol Cell Biochem 162: 153-158, 1996
Eugene F, Roth JR, Gilbert HS: The pyrogallol assay for superoxide dismutase: Absence of a glutathione artifact. Anal Biochem 137: 50-53, 1984
Aebi HE: Catalase. In: H.U. Bergmeyer (ed). Methods in Enzymatic Analysis. Verlag Chemie, Berlin, 1983, pp 278-282
Rotruck JT, Pope AL, Ganther HE: Selenium: Biochemical role as a component of glutathione peroxidase purification and assay. Science 179: 589-590, 1973
Esterbauer H, Cheeseman KH: Determination of aldehydic lipid peroxidation products: Malondialdehyde and 4-hydroxynonenal. Meth Enzymol 186: 408-411, 1990
Levine RL, Garland D, Oliver CN, Amici A, Climent I, Lenz A, Ahn B, Shaltiel S, Stadman ER: Determination of carbonyl content in oxidatively modified proteins. Meth Enzymol 186: 472-473, 1990
Lowry OH, Rosebrough NJ, Farr AL, Randall RJ: Protein measurement with the Folin phenol reagent. J Biol Chem 193: 265-275, 1951
Sambrook J, Fritsch EF, Maniatis T: Molecular Cloning. A Laboratory. Cold Spring Harbor Laboratory Press, New York, 1989
Cederberg J, Galli J, Luthman H, Eriksson UJ: Increased mRNA levels of Mn-SOD and catalase in embryos of diabetic rats from a malformation-resistant strain. Diabetes 49: 101-107, 2000
Osumi T, Hashimoto T: Acyl CoA oxidase of rat liver: A new enzyme for fatty acid oxidation. Biochim Biophys Res Commun 83: 479-485, 1978
Salahudeen AK: Role of lipid peroxidation in H2O2-induced renal epithelial (LLC-PK1) cell injury. Am J Physiol 268: F30-F38, 1995
Yan H, Harding JJ: Glycation-induced inactivation and loss of antigenicity of catalase and superoxide dismutase. Biochem J 328: 599-605, 1997
Kono Y, Fridovich I: Superoxide radical inhibits catalase. J Biol Chem 257: 5751-5754, 1982
Matkovics B, Varga SI, Szabo L, Witas H: The effect of diabetes on the activities of the peroxide metabolism enzymes. Horm Metab Res 14: 77-79, 1982
Yadav P, Sarkar S, Bhatnagar D: Lipid peroxidation and antioxidant enzymes in erythrocytes and tissues in aged diabetic rats. Ind J Exp Biol 35: 389-392, 1997
Reddi AS, Bollineni JS: Renal cortical expression of mRNAs for antioxidant enzymes in normal and diabetic rat. Biochim Biophys Res Commun 235: 598-601, 1997
Sechi LA, Ceriello A, Griffin CA, Catena C, Amstad P, Schambelan M, Bartoli E: Renal antioxidant enzyme mRNA levels are increased in rats with experimental diabetes mellitus. Diabetologia 40: 23-29, 1997
Tagami S, Kondo T, Yoshida K, Hirokawa J, Ohtsuka Y, Kawakami Y: Effect of insulin on impaired antioxidant activities in aortic endothelial cells from diabetic rabbits. Metabolism 41: 1053-1058, 1992
Shull S, Heintz NH, Periasamy M, Manohar M, Janssen YM, Marsh JP, Mossman BT: Differential regulation of antioxidant enzymes in response to oxidants. J Biol Chem 266: 24398-24403, 1991
Loven DP, Schedl HP, Oberley LW, Wilson HD, Bruch L, Niehaus CN: Superoxide dismutase in the intestinal mucosa of the streptozotocin-diabetic rat. Endocrinology 111: 737-742, 1982
Kamata K, Kobayashi T: Changes in superoxide dismutase mRNA expression by streptozotocin-induced diabetes. Br J Pharmacol 119: 583-589, 1996
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Limaye, P.V., Raghuram, N. & Sivakami, S. Oxidative stress and gene expression of antioxidant enzymes in the renal cortex of streptozotocin-induced diabetic rats. Mol Cell Biochem 243, 147–152 (2003). https://doi.org/10.1023/A:1021620414979
Issue Date:
DOI: https://doi.org/10.1023/A:1021620414979