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Concerted action of p62 and Nrf2 protects cells from palmitic acid-induced lipotoxicity

Authors
 Jeong Su Park  ;  Dong Hoon Kang  ;  Da Hyun Lee  ;  Soo Han Bae 
Citation
 BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, Vol.466(1) : 131-137, 2015 
Journal Title
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
ISSN
 0006-291X 
Issue Date
2015
MeSH
Adaptor Proteins, Signal Transducing/metabolism* ; Animals ; Apoptosis ; Autophagy ; Cell Line ; Cytoskeletal Proteins/metabolism* ; Heat-Shock Proteins/metabolism* ; Kelch-Like ECH-Associated Protein 1 ; Mice ; NF-E2-Related Factor 2/metabolism* ; Oxidative Stress ; Palmitic Acid/metabolism* ; Proteolysis* ; Reactive Oxygen Species/metabolism ; Sequestosome-1 Protein
Keywords
Autophagy ; FFA ; Keap1 ; Nrf2 ; PA ; ROS ; p62
Abstract
Nonalcoholic fatty liver disease (NAFLD), frequently associated with obesity and diabetes mellitus, is caused by the accumulation of excess fatty acids within liver cells. Palmitic acid (PA), a common saturated fatty acid found in mammals, induces the generation of reactive oxygen species (ROS) and elicits apoptotic cell death, known as lipotoxicity. However, protective mechanisms against PA-induced lipotoxicity have not been elucidated. In this study, we aimed to clarify the role of p62, an adapter protein in the autophagic process, as well as the nuclear factor erythroid 2-related factor 2 (Nrf2)-Kelch-like ECH-associated protein 1 (Keap1) pathway, in protecting cells from PA-induced lipotoxicity. The Nrf2-Keap1 pathway is essential for the protection of cells from oxidative stress. p62 enhances its binding to Keap1 and leads to Nrf2 activation. Here, we show that PA potentiates Keap1 degradation and thereby activates the transcription of Nrf2 target genes partially through autophagy. Furthermore, this PA-mediated Keap1 degradation depends on p62. Correspondingly, a lack of p62 attenuates the PA-mediated Nrf2 activation and increases the susceptibility of cells to oxidative stress. These results indicate that p62 plays an important role in protecting cells against lipotoxicity through Keap1 degradation-mediated Nrf2 activation.
Full Text
http://www.sciencedirect.com/science/article/pii/S0006291X1530512X
DOI
10.1016/j.bbrc.2015.08.120
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
Lee, Da Hyun(이다현) ORCID logo https://orcid.org/0000-0002-5412-6878
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/141328
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