title: Early molecular events in the development of the diabetic cardiomyopathy.
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.
authors.affiliation: Department of Radiology, University of Bonn, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Mönkemann
authors.forename: A S
authors.initials: AS
authors.lastname: De Vriese
authors.forename: H J
authors.initials: HJ
authors.lastname: Blom
authors.forename: L A J
authors.initials: LA
authors.lastname: Kluijtmans
authors.forename: S G
authors.initials: SG
authors.lastname: Heil
authors.forename: H H
authors.initials: HH
authors.lastname: Schild
authors.forename: O
authors.initials: O
authors.lastname: Golubnitschaja
mesh_terms: D000818:Animals; D009202:Cardiomyopathies / Q000209:etiology* / Q000378:metabolism*; D018899:CpG Islands; D019938:Cyclin D1 / Q000235:genetics* / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000235:genetics* / Q000378:metabolism; D004249:DNA Damage; D019175:DNA Methylation; D003921:Diabetes Mellitus, Experimental / Q000150:complications* / Q000378:metabolism*; D005260:Female; D032383:Myocytes, Cardiac / Q000502:physiology; D011401:Promoter Regions, Genetic; D051381:Rats; D017208:Rats, Wistar
chemical_list: C493958:Cdkn1a protein, rat; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D019938:Cyclin D1