Unknown

Dataset Information

0

Caveolin-1 expression is required for the development of pulmonary emphysema through activation of the ATM-p53-p21 pathway.


ABSTRACT: Free radicals play a role in aging and age-related human diseases, including pulmonary emphysema. Cigarette smoke represents a source of oxidants and is considered an environmental hazard that causes pulmonary emphysema. Here, we show that caveolin-1 activates ataxia telangiectasia-mutated (ATM) after oxidative stress by sequestering the ATM inhibitor, the catalytic subunit of protein phosphatase 2A, into caveolar membranes. We demonstrate that cigarette smoke extracts promote stress-induced premature senescence in wild type but not caveolin-1 null lung fibroblasts and that caveolin-1 expression is required for activation of the ATM-p53-p21(Waf1)(/)(Cip1) pathway following stimulation with cigarette smoke extracts in vitro. In vivo studies show that caveolin-1 expression is necessary for cigarette smoking-induced senescence of lung fibroblasts and pulmonary emphysema. These findings bring new insights into the molecular mechanism underlying free radical activation of the ATM-p53 pathway and indicate that caveolin-1 is a novel therapeutic target for the treatment and/or prevention of pulmonary emphysema.

SUBMITTER: Volonte D 

PROVIDER: S-EPMC2645811 | BioStudies | 2009-01-01T00:00:00Z

REPOSITORIES: biostudies

Similar Datasets

2009-01-01 | S-EPMC2643077 | BioStudies
2015-01-01 | S-EPMC4478793 | BioStudies
2019-01-01 | S-EPMC6689060 | BioStudies
2015-01-01 | S-EPMC4604604 | BioStudies
1000-01-01 | S-EPMC3208661 | BioStudies
2008-01-01 | S-EPMC2493196 | BioStudies
1000-01-01 | S-EPMC3366403 | BioStudies
2013-01-01 | S-EPMC3674284 | BioStudies
2009-01-01 | S-EPMC2692066 | BioStudies
2006-01-01 | S-EPMC2647641 | BioStudies