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p62 prevents carbonyl cyanide m-chlorophenyl hydrazine (CCCP)-induced apoptotic cell death by activating Nrf2

Authors
 Jeong Su Park  ;  Dong Hoon Kang  ;  Soo Han Bae 
Citation
 BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, Vol.464(4) : 1139-1144, 2015 
Journal Title
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
ISSN
 0006-291X 
Issue Date
2015
MeSH
Adaptor Proteins, Signal Transducing/metabolism* ; Animals ; Apoptosis/drug effects ; Apoptosis/physiology ; Carbonyl Cyanide m-Chlorophenyl Hydrazone/pharmacology* ; Cell Line ; Fibroblasts/cytology* ; Fibroblasts/drug effects ; Fibroblasts/metabolism* ; Heat-Shock Proteins/metabolism* ; Mice ; NF-E2-Related Factor 2/metabolism* ; Oxidative Stress/drug effects ; Oxidative Stress/physiology* ; Reactive Oxygen Species/metabolism* ; Sequestosome-1 Protein
Keywords
Autophagy ; CCCP ; Keap1 ; Nrf2 ; p62
Abstract
Carbonyl cyanide m-chlorophenyl hydrazone (CCCP) is a mitochondrial depolarizing agent that induces reactive oxygen species (ROS)-mediated cell death. The Nrf2-Keap1 pathway is crucial for the elimination of ROS in stressed cells. However, the molecular mechanism underlying the regulation of the Nrf2-Keap1 pathway in CCCP-induced cell death is unknown. In this study, we demonstrated that CCCP promotes Keap1 degradation, and thereby activates Nrf2. This CCCP-mediated Keap1 degradation is partly dependent on autophagy. Moreover, CCCP-induced Keap1 degradation is mainly reliant on p62, which functions as an adaptor protein during selective autophagy. Lack of p62 blocked CCCP-induced Keap1 degradation and inhibited Nrf2 activation, and thereby increased the accumulation of ROS. Ablation of p62 increased the susceptibility of cells to oxidative stress. These results indicate that p62 plays an important role in protecting cells against oxidative stress through Keap1 degradation-mediated Nrf2 activation.
Full Text
http://www.sciencedirect.com/science/article/pii/S0006291X15303235
DOI
10.1016/j.bbrc.2015.07.093
Appears in Collections:
1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
Yonsei Authors
Park, Jeong Su(박정수) ORCID logo https://orcid.org/0000-0003-4551-4294
Bae, Soo Han(배수한) ORCID logo https://orcid.org/0000-0002-8007-2906
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/141061
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