Document Detail


Cigarette smoke extract induces activation of beta-catenin/TCF signaling through inhibiting GSK3beta in human alveolar epithelial cell line.
MedLine Citation:
PMID:  19429245     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Cigarette smoke is known to have various injurious and cytotoxic effects on alveolar epithelial cells. However, the mechanism about the effects caused by cigarette smoke on alveolar epithelial cells remains unclear. In the present study, we first validated that cigarette smoke extract (CSE) impaired the viability of alveolar epithelial cells (A549 cells) and resulted in some morphological changes. Next, we found that glycogen synthase kinase 3beta (GSK3beta) was highly expressed in A549 cells, and CSE significantly inhibited GSK3beta by reducing GSK3beta expression and increasing inactive phosphorylated GSK3beta. It was also observed that CSE promoted beta-catenin accumulation and nuclear translocation, and further activated beta-catenin/TCF signaling. Finally, we demonstrated that GSK3beta over-expression promoted the degradation of beta-catenin and abolished beta-catenin/TCF transcriptional activity that was induced by CSE in alveolar epithelial cells. These results suggest that CSE induces the activation of beta-catenin/TCF signaling through inhibiting GSK3beta, implying a possible mechanism responsible for the injurious and cytotoxic effects on alveolar epithelial cell caused by cigarette smoke.
Authors:
Dan Tian; Min Zhu; Jiansha Li; Yan Ma; Renliang Wu
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-02-10
Journal Detail:
Title:  Toxicology letters     Volume:  187     ISSN:  0378-4274     ISO Abbreviation:  Toxicol. Lett.     Publication Date:  2009 May 
Date Detail:
Created Date:  2009-05-11     Completed Date:  2009-05-26     Revised Date:  2011-11-02    
Medline Journal Info:
Nlm Unique ID:  7709027     Medline TA:  Toxicol Lett     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  58-62     Citation Subset:  IM    
Affiliation:
Department of Pathology, Shanghai First People's Hospital, Shanghai Jiao Tong University Affiliated First People's Hospital, Shanghai 200080, PR China.
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MeSH Terms
Descriptor/Qualifier:
Active Transport, Cell Nucleus / drug effects
Cell Line, Tumor
Cell Nucleus / drug effects,  metabolism
Cell Survival / drug effects
Enzyme Inhibitors / adverse effects
Epithelial Cells / drug effects*,  enzymology
Glycogen Synthase Kinase 3 / antagonists & inhibitors,  metabolism*
Humans
Lung Neoplasms
Nicotine / analysis
Plants, Toxic / chemistry
Pulmonary Alveoli / drug effects*,  enzymology
Signal Transduction / drug effects*
Smoke / adverse effects*,  analysis
Tars / analysis
Tobacco / chemistry*
beta Catenin / metabolism*
Chemical
Reg. No./Substance:
0/Enzyme Inhibitors; 0/Smoke; 0/Tars; 0/beta Catenin; 0/tobacco tar; 54-11-5/Nicotine; EC 2.7.11.1/glycogen synthase kinase 3 beta; EC 2.7.11.26/Glycogen Synthase Kinase 3

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


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