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Oxidative and nitrosative stress induces peroxiredoxins in pancreatic beta cells
1Department of Medical Biochemistry and Molecular Biology, Ernst-Moritz-Arndt-University Greifswald, Germany.
Aims/Hypothesis:
Insulin-producing beta cells are destroyed by oxidative and nitrosative stress during the pathogenesis of Type I (insulin-dependent) diabetes mellitus. These cells are more sensitive than others due to their deficiency of well known antioxidant enzymes like superoxide dismutase, glutathione peroxidase and catalase. However the peroxiredoxins discovered in the past decade form a large family of highly conserved thioredoxin-dependent peroxide reductases, which are present in most tissues. We investigated whether peroxiredoxins I and II are present in pancreatic beta cells and if they are inducible by oxidative and nitrosative stress.
Methods:
To detect these enzymes in insulin-producing beta cells we used semiquantitative RT-PCR, western blots and immunohistochemistry. The expression of peroxiredoxins I and II was analysed after treatment with cytokines, hydrogen peroxide, alloxan or streptozotocin in the rat insulinoma cells INS-1 using RT-PCR and western blots.
Results:
We show that peroxiredoxins I and II are present in the cytoplasm of pancreatic islet cells as well as in insulinoma cell lines beta TC6-F7 and INS-1. Peroxiredoxins I and II were up-regulated by all stress agents used.
Conclusion/Interpretation:
Beta cells, undersupplied with well characterized antioxidant enzymes, possess an additional antioxidant system which is inducible by oxidative as well as nitrosative stress.
Insights
Pancreatic beta cells, crucial for diabetes management, possess an inducible antioxidant system involving peroxiredoxins I and II. These enzymes offer protection against oxidative and nitrosative stress, vital for beta cell survival.
Area of Science:
- Cell Biology
- Biochemistry
- Endocrinology
Background:
- Type I diabetes involves oxidative and nitrosative stress damaging insulin-producing beta cells.
- Beta cells have limited known antioxidant enzymes, increasing their vulnerability.
- Peroxiredoxins (PRDXs) are a family of antioxidant enzymes found in most tissues.
Purpose of the Study:
- To determine the presence of peroxiredoxins I and II in pancreatic beta cells.
- To investigate if peroxiredoxins I and II expression is inducible by oxidative and nitrosative stress.
Main Methods:
- Semiquantitative RT-PCR, western blots, and immunohistochemistry were used to detect PRDX I and II.
- Rat insulinoma cell lines (INS-1, beta TC6-F7) were treated with cytokines, hydrogen peroxide, alloxan, or streptozotocin.
- Gene and protein expression levels of PRDX I and II were analyzed post-treatment.
Main Results:
- Peroxiredoxins I and II were detected in the cytoplasm of pancreatic islet cells and beta cell lines.
- Treatment with various stress agents significantly upregulated the expression of peroxiredoxins I and II.
Conclusions:
- Pancreatic beta cells possess an additional antioxidant defense system beyond well-characterized enzymes.
- This system, involving peroxiredoxins I and II, is inducible and provides protection against oxidative and nitrosative stress.
- This finding has implications for understanding beta cell resilience in diabetes pathogenesis.