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Title 

p62 sequestosome 1/light chain 3b complex confers cytoprotection on lung epithelial cells after hyperoxia

 

과산소 조건에서 폐상피세포를 보호하는 p62와 LC3B 복합체

Authors 

X LiangS Q WeiSeon-Jin LeeJ K FungM ZhangA TanakaA M K ChoiY Jin

Publisher 

American Thoracic Society

Issue Date 

2013

Citation 

American Journal of Respiratory Cell and Molecular Biology, vol. 48, no. 4, pp. 489-496

Keywords 

ApoptosisHyperoxiaLC3bP62/SQSTM1Tbid

Abstract 

Lung epithelial cell death is a prominent feature of hyperoxic lung injury, and has been considered a very important underlying mechanism of acute lung injury (ALI) and acute respiratory distress syndrome(ARDS). Here we report on a novel mechanism involved in epithelial cytoprotection and homeostasis after oxidative stress. p62 (sequestosome 1; SQSTM1) is a ubiquitously expressed cellular protein. It interacts with ubiquitinated proteins and autophagic marker light chain 3b (LC3b), thus mediating the degradation of selective targets. In this study, we explored the role of p62 in mitochondria-mediated cell death after hyperoxia. Lung alveolar epithelial cells demonstrate abundant p62 expression, and p62 concentrations are up-regulated by oxidative stress at both the protein and mRNA levels. The p62/LC3b complex interacts with Fas and truncated BID (tBID) physically. These interactions abruptly diminish after hyperoxia. The deletion of p62 robustly increases tBID and cleaved caspase-3, implying an antiapoptotic effect. This antiapoptotic effect of p62 is further confirmed by measuring caspase activities, cleaved poly ADP ribose polymerase, and cell viability. The deletion of the p62 PBI domain or the ubiquitin-associated domain both lead to elevated tBID, cleaved caspase-3, and significantly more cell death after hyperoxia. Moreover, p62 traffics in an opposite direction with LC3b after hyperoxia, leading to the dissociation of the p62/Cav-1/LC3b/BIDcomplex. Subsequently, the LC3b-mediated lysosomal degradation of tBID is eliminated. Taken together, our data suggest that the p62/LC3b complex regulates lung alveolar epithelial cell homeostasis and cytoprotection after hyperoxia.

ISSN 

1044-1549

Link 

http://dx.doi.org/10.1165/rcmb.2012-0017OC

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2019-05-02


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