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

Title
Concerted action of p62 and Nrf2 protects cells from palmitic acid-induced lipotoxicity
Authors
Park, Jeong SuKang, Dong HoonLee, Da HyunBae, Soo Han
Ewha Authors
강동훈
SCOPUS Author ID
강동훈scopus
Issue Date
2015
Journal Title
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
ISSN
0006-291XJCR Link1090-2104JCR Link
Citation
vol. 466, no. 1, pp. 131 - 137
Keywords
FFAPAROSp62AutophagyNrf2Keap1
Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
Indexed
SCI; SCIE; SCOPUS WOS scopus
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 Keapl and leads to Nrf2 activation. Here, we show that PA potentiates Keapl 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 Keapl degradation-mediated Nrf2 activation. (C) 2015 Elsevier Inc. All rights reserved.
DOI
10.1016/j.bbrc.2015.08.120
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연구기관 > 세포항상성연구센터 > Journal papers
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