Autophagy regulates ROS-induced cellular senescence via p21 in a p38 MAPKα dependent manner

Yi Luo, Ping Zou, Jing Zou, Jie Wang, Daohong Zhou, Lingbo Liu

Research output: Contribution to journalArticlepeer-review

77 Scopus citations

Abstract

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 H 2O 2 induced both senescence and autophagy. Downregulation of autophagy protein 5 (Atg5) with Atg5 siRNA inhibited not only autophagy but also senescence induced by H 2O 2. Further studies showed that Atg5 regulates H 2O 2-induced senescence primarily by up-regulating the expression of p21 at the level of post-transcription. In addition, we examined the mechanisms by which H 2O 2 induces autophagy in WI38 cells. Our results revealed that H 2O 2 increases autophagy independent of the mammalian target of rapamycin (mTOR) negative feedback pathway. Instead, the induction of autophagy by H 2O 2 depends on the induction of intracellular production of reactive oxygen species (ROS) and activation of the p38 mitogen-activated protein kinase α (p38 MAPKα) pathway.

Original languageEnglish (US)
Pages (from-to)860-867
Number of pages8
JournalExperimental Gerontology
Volume46
Issue number11
DOIs
StatePublished - Nov 2011
Externally publishedYes

Keywords

  • Autophagy
  • Oxidative stress
  • P21
  • P38 mitogen-activated protein kinase α
  • Reactive oxygen species
  • Senescence

ASJC Scopus subject areas

  • Biochemistry
  • Aging
  • Molecular Biology
  • Genetics
  • Endocrinology
  • Cell Biology

Fingerprint

Dive into the research topics of 'Autophagy regulates ROS-induced cellular senescence via p21 in a p38 MAPKα dependent manner'. Together they form a unique fingerprint.

Cite this