Document Detail


Insufficient autophagy promotes bronchial epithelial cell senescence in chronic obstructive pulmonary disease.
MedLine Citation:
PMID:  22934255     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Tobacco smoke-induced accelerated cell senescence has been implicated in the pathogenesis of chronic obstructive pulmonary disease (COPD). Cell senescence is accompanied by the accumulation of damaged cellular components suggesting that in COPD, inhibition of autophagy may contribute to cell senescence. Here we look at whether autophagy contributes to cigarette smoke extract (CSE) - induced cell senescence of primary human bronchial epithelial cells (HBEC), and further evaluate p62 and ubiquitinated protein levels in lung homogenates from COPD patients. We demonstrate that CSE transiently induces activation of autophagy in HBEC, followed by accelerated cell senescence and concomitant accumulation of p62 and ubiquitinated proteins. Autophagy inhibition further enhanced accumulations of p62 and ubiquitinated proteins, resulting in increased senescence and senescence-associated secretory phenotype (SASP) with interleukin (IL)-8 secretion. Conversely, autophagy activation by Torin1, a mammalian target of rapamycin (mTOR inhibitor), suppressed accumulations of p62 and ubiquitinated proteins and inhibits cell senescence. Despite increased baseline activity, autophagy induction in response to CSE was significantly decreased in HBEC from COPD patients. Increased accumulations of p62 and ubiquitinated proteins were detected in lung homogenates from COPD patients. Insufficient autophagic clearance of damaged proteins, including ubiquitinated proteins, is involved in accelerated cell senescence in COPD, suggesting a novel protective role for autophagy in the tobacco smoke-induced senescence-associated lung disease, COPD.
Authors:
Satoko Fujii; Hiromichi Hara; Jun Araya; Naoki Takasaka; Jun Kojima; Saburo Ito; Shunsuke Minagawa; Yoko Yumino; Takeo Ishikawa; Takanori Numata; Makoto Kawaishi; Jun Hirano; Makoto Odaka; Toshiaki Morikawa; Stephen Nishimura; Katsutoshi Nakayama; Kazuyoshi Kuwano
Related Documents :
24001715 - A combined approach facilitates the reliable detection of human spermatogonia in vitro.
24850425 - Foxp3(+) regulatory t cells promote lung epithelial proliferation.
23071815 - Zfp423 promotes adipogenic differentiation of bovine stromal vascular cells.
23851005 - Cytotoxic responses in bc3h1 myoblast cell lines exposed to 1-desulfoyessotoxin.
2022695 - Membrane potential and amino acid transport in a mutant chinese hamster ovary cell line.
21064125 - Microfluidic approaches for the fabrication of gradient crosslinked networks based on p...
Publication Detail:
Type:  JOURNAL ARTICLE    
Journal Detail:
Title:  Oncoimmunology     Volume:  1     ISSN:  2162-402X     ISO Abbreviation:  Oncoimmunology     Publication Date:  2012 Aug 
Date Detail:
Created Date:  2012-8-30     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101570526     Medline TA:  Oncoimmunology     Country:  -    
Other Details:
Languages:  ENG     Pagination:  630-641     Citation Subset:  -    
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:

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


Previous Document:  Environment-mediated drug resistance in Bcr/Abl-positive acute lymphoblastic leukemia.
Next Document:  Tumor antigen specific iTreg accumulate in the tumor microenvironment and suppress therapeutic vacci...