0 115

Cited 15 times in

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

 Jeong Su Park  ;  Dong Hoon Kang  ;  Da Hyun Lee  ;  Soo Han Bae 
 Biochemical and Biophysical Research Communications, Vol.466(1) : 131-137, 2015 
Journal Title
 Biochemical and Biophysical Research Communications 
Issue Date
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
Appears in Collections:
1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
Yonsei Authors
박정수(Park, Jeong Su) ORCID logo https://orcid.org/0000-0003-4551-4294
배수한(Bae, Soo Han) ORCID logo https://orcid.org/0000-0002-8007-2906
RIS (EndNote)
XLS (Excel)
사서에게 알리기


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.