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Amino Acids. 2002;23(1-3):331-6.

Early molecular events in the development of the diabetic cardiomyopathy.

Author information

1
Department of Radiology, University of Bonn, Germany.

Abstract

Oxidative damage to DNA has been well documented in cardiac cells isolated from diabetic patients and rats with streptozotocin-induced diabetes mellitus (DM). This study evaluates possible molecular mechanisms for early events in the development of DM-induced cardiomyopathy.

METHODS:

To analyze the mechanism of overexpression of p21(WAF1/CIP1) and inhibition of cyclin D(1) expression in cardiomyocytes of diabetic rats we examined the methylation status of these genes by MS-PCR and assessed the possibility of epigenetic control of their expression.

RESULTS:

We found that the steady-state expression of both genes is influenced by their methylation status, as an epigenetic event, of their 5'-flanking regions upon development of diabetes.

CONCLUSIONS:

Oxidative damage contributes to the development of cardiomyopathy via p53-dependent activation of cardiac cell death. This pathway includes de novomethylation of the P53-inducible p21(WAF1/CIP1)-gene encoding a protein which binds to and inhibits a broad range of cyclin-cyclin-dependent kinase complexes.

PMID:
12373555
DOI:
10.1007/s00726-001-0146-y
[Indexed for MEDLINE]

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