期刊
EXPERIMENTAL GERONTOLOGY
卷 46, 期 11, 页码 860-867出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.exger.2011.07.005
关键词
Oxidative stress; Reactive oxygen species; Autophagy; Senescence; p21; p38 mitogen-activated protein kinase alpha
资金
- National Natural Science Foundation of China [30871097]
- National Institute of Health of US [CA122023, AI080421]
Oxidative stress induces not only senescence but also autophagy in a variety of mammalian cells. However, the relationship between these two has not been well established and thus, was investigated in the present study using WI38 human diploid fibroblasts (WI38 cells) as a model system. Our results showed that exposure of WI38 cells to H2O2 induced both senescence and autophagy. Downregulation of autophagy protein 5 (Atg5) with Atg5 siRNA inhibited not only autophagy but also senescence induced by H2O2. Further studies showed that Atg5 regulates H2O2-induced senescence primarily by up-regulating the expression of p21 at the level of post-transcription. In addition, we examined the mechanisms by which H2O2 induces autophagy in WI38 cells. Our results revealed that H2O2 increases autophagy independent of the mammalian target of rapamycin (mTOR) negative feedback pathway. Instead, the induction of autophagy by H2O2 depends on the induction of intracellular production of reactive oxygen species (ROS) and activation of the p38 mitogen-activated protein kinase alpha (p38 MAPK alpha) pathway. (C) 2011 Elsevier Inc. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据