Document Detail

p62 sequestosome 1/light chain 3b complex confers cytoprotection on lung epithelial cells after hyperoxia.
MedLine Citation:
PMID:  23333919     Owner:  NLM     Status:  MEDLINE    
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/BID complex. 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.
Xiaoliang Liang; Shu-Quan Wei; Seon-Jin Lee; James K Fung; Meng Zhang; Akihiko Tanaka; Augustine M K Choi; Yang Jin
Related Documents :
24068039 - Erk pathway is activated in bare-fenps-induced autophagy.
22920899 - Hsp60 as a drug target.
23007469 - Protumor and antitumor functions of neutrophil granulocytes.
23146149 - Nanoscale imaging of the candida-macrophage interaction using correlated fluorescence-a...
23507439 - Plasmids expressing porcine interferon gamma up-regulate pro-inflammatory cytokine and ...
23541899 - Implications for interleukin-33 in solid organ transplantation.
24124799 - Oral inflammation, a role for antimicrobial peptide modulation of cytokine and chemokin...
2070879 - The immunopathology of intraocular tumour rejection.
20339379 - Cathepsin b facilitates autophagy-mediated apoptosis in sparc overexpressed primitive n...
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  American journal of respiratory cell and molecular biology     Volume:  48     ISSN:  1535-4989     ISO Abbreviation:  Am. J. Respir. Cell Mol. Biol.     Publication Date:  2013 Apr 
Date Detail:
Created Date:  2013-04-02     Completed Date:  2013-05-23     Revised Date:  2014-04-01    
Medline Journal Info:
Nlm Unique ID:  8917225     Medline TA:  Am J Respir Cell Mol Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  489-96     Citation Subset:  IM    
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
ADP Ribose Transferases / metabolism
Adaptor Proteins, Signal Transducing / metabolism*
BH3 Interacting Domain Death Agonist Protein / metabolism
Caspase 3 / metabolism
Caveolin 1 / metabolism
Cell Line
Epithelial Cells / metabolism*,  pathology
Heat-Shock Proteins / metabolism*
Hyperoxia / metabolism*,  pathology
Lysosomes / metabolism,  pathology
Microtubule-Associated Proteins / metabolism*
Multiprotein Complexes / metabolism*
Oxidative Stress
Pulmonary Alveoli / metabolism*,  pathology
Grant Support
Reg. No./Substance:
0/Adaptor Proteins, Signal Transducing; 0/BH3 Interacting Domain Death Agonist Protein; 0/Bid protein, mouse; 0/Cav1 protein, mouse; 0/Caveolin 1; 0/Heat-Shock Proteins; 0/MAP1LC3 protein, mouse; 0/Microtubule-Associated Proteins; 0/Multiprotein Complexes; 0/Sqstm1 protein, mouse; EC 2.4.2.-/ADP Ribose Transferases; EC 3.4.22.-/Casp3 protein, mouse; EC 3.4.22.-/Caspase 3

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Previous Document:  Tamavidin 2-REV: an engineered tamavidin with reversible biotin-binding capability.
Next Document:  Synergy of IL-27 and TNF-? in regulating CXCL10 expression in lung fibroblasts: implications in airw...