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p62/SQSTM1 is required for the protection against endoplasmic reticulum stress-induced apoptotic cell death

Authors
 Jeong Su Park  ;  Sue Young Oh  ;  Da Hyun Lee  ;  Yu Seol Lee  ;  Su Haeng Sung  ;  Hye Won Ji  ;  Moon Joo Lee  ;  Yong-ho Lee  ;  Sue Goo Rhee  ;  Soo Han Bae 
Citation
 Free Radical Research, Vol.50(12) : 1408-1421, 2016 
Journal Title
 Free Radical Research 
ISSN
 1071-5762 
Issue Date
2016
MeSH
Animals ; Apoptosis/physiology ; Autophagy/drug effects ; Autophagy/physiology ; Cell Death/physiology ; Endoplasmic Reticulum Stress/physiology ; HEK293 Cells ; Humans ; Kelch-Like ECH-Associated Protein 1/metabolism ; Mice ; NF-E2-Related Factor 2/metabolism ; Oxidative Stress/physiology ; RNA-Binding Proteins/metabolism* ; Sequestosome-1 Protein/metabolism* ; Tunicamycin/pharmacology
Keywords
ER stress ; Keap1 ; Nrf2 ; Tunicamycin ; autophagy ; p62
Abstract
Endoplasmic reticulum (ER) stress is triggered by various cellular stresses that disturb protein folding or calcium homeostasis in the ER. To cope with these stresses, ER stress activates the unfolded protein response (UPR) pathway, but unresolved ER stress induces reactive oxygen species (ROS) accumulation leading to apoptotic cell death. However, the mechanisms that underlie protection from ER stress-induced cell death are not clearly defined. The nuclear factor erythroid 2-related factor 2 (Nrf2)-Kelch-like ECH-associated protein 1 (Keap1) pathway plays a crucial role in the protection of cells against ROS-mediated oxidative damage. Keap1 acts as a negative regulator of Nrf2 activation. In this study, we investigated the role of the Nrf2-Keap1 pathway in protection from ER stress-induced cell death using tunicamycin (TM) as an ER stress inducer. We found that Nrf2 is an essential protein for the prevention from TM-induced apoptotic cell death and its activation is driven by autophagic Keap1 degradation. Furthermore, ablation of p62, an adapter protein in the autophagy process, attenuates the Keap1 degradation and Nrf2 activation that was induced by TM treatment, and thereby increases susceptibility to apoptotic cell death. Conversely, reinforcement of p62 alleviated TM-induced cell death in p62-deficient cells. Taken together, these results demonstrate that p62 plays an important role in protecting cells from TM-induced cell death through Nrf2 activation.
Full Text
http://www.tandfonline.com/doi/abstract/10.1080/10715762.2016.1253073
DOI
10.1080/10715762.2016.1253073
Appears in Collections:
1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 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
이서구(Rhee, Sue Goo)
이용호(Lee, Yong Ho) ORCID logo https://orcid.org/0000-0002-6219-4942
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URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/152774
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