Mönkemann H, De Vriese A S, Blom H J, Kluijtmans L A J, Heil S G, Schild H H, Golubnitschaja O
Department of Radiology, University of Bonn, Germany.
Amino Acids. 2002;23(1-3):331-6. doi: 10.1007/s00726-001-0146-y.
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.
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.
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.
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.
在从糖尿病患者以及链脲佐菌素诱导的糖尿病（DM）大鼠分离出的心脏细胞中，DNA的氧化损伤已有充分记录。本研究评估了糖尿病诱导的心肌病发展早期事件的可能分子机制。
为分析糖尿病大鼠心肌细胞中p21（WAF1/CIP1）过表达和细胞周期蛋白D（1）表达受抑制的机制，我们通过甲基化特异性聚合酶链反应（MS-PCR）检测了这些基因的甲基化状态，并评估了其表达的表观遗传控制的可能性。
我们发现，在糖尿病发展过程中，作为一种表观遗传事件，这两个基因的稳态表达受其5'侧翼区域甲基化状态的影响。
氧化损伤通过p53依赖的心肌细胞死亡激活促进心肌病的发展。该途径包括P53诱导的p21（WAF1/CIP1）基因的从头甲基化，该基因编码一种与多种细胞周期蛋白 - 细胞周期蛋白依赖性激酶复合物结合并抑制其活性的蛋白质。
