Unterluggauer Hermann, Micutkova Lucia, Lindner Herbert, Sarg Bettina, Hernebring Malin, Nystrom Thomas, Jansen-Dürr Pidder
Institute for Biomedical Aging Research, Austrian Academy of Sciences, Rennweg 10, 6020, Innsbruck, Austria.
Biogerontology. 2009 Jun;10(3):299-309. doi: 10.1007/s10522-008-9193-z. Epub 2008 Nov 14.
Cellular senescence is known as a potent mechanism of tumor suppression, and cellular senescence in vitro also reflects at least some features of aging in vivo. The Free Radical Theory of aging suggests that reactive oxygen species are important causative agents of aging and cellular senescence. Besides damage of nucleic acids and lipids, also oxidative modifications of proteins have been described as potential causative events in the senescence response. However, the identity of protein targets for post-translational modifications in senescent cells has remained unclear. In the present communication, we analyzed the occurrence of oxidative posttranslational modifications in senescent human endothelial cells and dermal fibroblasts. We found a significant increase in the level of protein carbonyls and AGE modification with senescence in both cell types. Using 2D-Gel electrophoresis and Western Blot we found that heat shock cognate protein 70 is a bona fide target for AGE modification in human fibroblasts.
细胞衰老被认为是一种强大的肿瘤抑制机制，体外细胞衰老也至少反映了体内衰老的一些特征。衰老的自由基理论表明，活性氧是衰老和细胞衰老的重要致病因素。除了核酸和脂质的损伤外，蛋白质的氧化修饰也被描述为衰老反应中的潜在致病事件。然而，衰老细胞中翻译后修饰的蛋白质靶点的身份仍不清楚。在本通讯中，我们分析了衰老的人内皮细胞和真皮成纤维细胞中氧化翻译后修饰的发生情况。我们发现，在这两种细胞类型中，蛋白质羰基水平和衰老过程中的晚期糖基化终末产物（AGE）修饰都显著增加。使用二维凝胶电泳和蛋白质印迹法，我们发现热休克同源蛋白70是人类成纤维细胞中AGE修饰的真正靶点。
