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Renal cortical expression of mRNAs for antioxidant enzymes in normal and diabetic rats
1Department of Medicine, UMDNJ-New Jersey Medical School, Newark 07103, USA.
Abstract:
Increased oxidative stress has been implicated in the development of vascular complications of diabetes. In this study, we examined the hypothesis whether chronic hyperglycemia induces oxidative stress by lowering renal expression and activity of antioxidant enzymes and a decrease in glutathione, an antioxidant, in streptozotocin diabetic rats. The results show that the expression of mRNAs for Cu/Zn superoxide dismutase and glutathione peroxidase was significantly increased and that of catalase was decreased in diabetic rats. However, the superoxide dismutase activity was significantly lower in diabetic than normal glomeruli, whereas the activities of the other two enzymes correlated with their mRNA expression. Total glutathione content was significantly decreased in diabetic compared to normal glomeruli. The data suggest that hyperglycemia induces oxidative stress by overexpressing rather than lowering certain antioxidant enzyme mRNAs in the kidney of diabetic rats. Enhanced nonenzymatic glycation of enzyme protein seems to be the cause for the observed decrease in glomerular superoxide dismutase activity.
Insights
Chronic hyperglycemia in diabetic rats increases oxidative stress by altering kidney antioxidant enzyme expression and glutathione levels, with glycation impairing enzyme activity.
Area of Science:
- Biochemistry
- Molecular Biology
- Diabetology
Background:
- Oxidative stress is linked to diabetic vascular complications.
- The role of antioxidant enzymes and glutathione in diabetic nephropathy requires further elucidation.
Purpose of the Study:
- To investigate if chronic hyperglycemia induces oxidative stress by altering renal antioxidant enzyme expression and glutathione levels in diabetic rats.
- To examine the impact of hyperglycemia on the activity of key antioxidant enzymes, including superoxide dismutase, catalase, and glutathione peroxidase.
Main Methods:
- Streptozotocin-induced diabetic rat model.
- Quantification of antioxidant enzyme mRNA expression (superoxide dismutase, catalase, glutathione peroxidase).
- Measurement of glomerular enzyme activities and total glutathione content.
Main Results:
- Diabetic rats showed increased mRNA expression for Cu/Zn superoxide dismutase and glutathione peroxidase, but decreased catalase mRNA.
- Glomerular superoxide dismutase activity was significantly reduced in diabetic rats, despite increased mRNA.
- Total glutathione content was significantly decreased in diabetic glomeruli.
Conclusions:
- Hyperglycemia induces oxidative stress in the kidney, partly by altering antioxidant enzyme mRNA expression.
- Nonenzymatic glycation of proteins likely explains the decreased glomerular superoxide dismutase activity in diabetic rats.