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Reduction of activity, but no decrease in concentration, of erythrocyte Cu,Zn-superoxide dismutase by hyperglycaemia
M Kotake1, R Shinohara, K Kato
1Department of Internal Medicine, Fujita Health University School of Medicine and Hygiene, Aichi, Japan.
Summary
Erythrocyte copper, zinc-superoxide dismutase (SOD) activity is lower in Type 2 diabetes patients, correlating with HbA1c. Enzyme concentration remains unchanged, suggesting inactivation, not reduced production, due to hyperglycemia.
Area of Science:
- Biochemistry
- Cell Biology
- Endocrinology
Background:
- Copper, zinc-superoxide dismutase (Cu,Zn-SOD) is crucial for cellular defense against oxidative stress.
- Erythrocyte Cu,Zn-SOD activity is implicated in various diseases, including diabetes mellitus (DM).
- Understanding Cu,Zn-SOD's role in Type 2 DM pathogenesis is vital for metabolic disease research.
Purpose of the Study:
- To investigate alterations in erythrocyte Cu,Zn-SOD activity and concentration in Type 2 DM patients.
- To compare these changes with indicators of glycemic control, such as HbA1c and fasting blood glucose.
- To elucidate the relationship between hyperglycemia, Cu,Zn-SOD inactivation, and erythrocyte enzyme levels.
Main Methods:
- Quantification of Cu,Zn-SOD enzymatic activity in erythrocytes.
- Measurement of Cu,Zn-SOD protein concentration in erythrocytes.
- Correlation analysis with clinical parameters: HbA1c, fasting blood glucose, plasma cholesterol, and triglycerides.
Main Results:
- Erythrocyte Cu,Zn-SOD activity was significantly reduced in Type 2 DM patients compared to healthy controls.
- Enzyme activity showed a negative correlation with HbA1c levels.
- No significant difference in erythrocyte Cu,Zn-SOD concentration was observed between diabetic and control groups, nor did it correlate with activity or HbA1c.
Conclusions:
- The findings suggest that hyperglycemia in Type 2 DM leads to the inactivation of erythrocyte Cu,Zn-SOD, rather than a decrease in its concentration.
- Glycosylation of the enzyme's active site is a potential mechanism for this inactivation.
- These results highlight a specific molecular consequence of chronic hyperglycemia on antioxidant defense in red blood cells.