Cigarette Smoke Induces Cellular Senescence via Werner's Syndrome Protein Down-regulation

Toru Nyunoya; Martha M Monick; Aloysius L Klingelhutz; Heather Glaser; Jeffrey R Cagley; Charles O Brown; Eiyu Matsumoto; Nukhet Aykin-Burns; Douglas R Spitz; Junko Oshima; Gary W Hunninghake

doi:10.1164/rccm.200802-320OC

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Cigarette Smoke Induces Cellular Senescence via Werner's Syndrome Protein Down-regulation

Journal article

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Cigarette Smoke Induces Cellular Senescence via Werner's Syndrome Protein Down-regulation

Toru Nyunoya, Martha M Monick, Aloysius L Klingelhutz, Heather Glaser, Jeffrey R Cagley, Charles O Brown, Eiyu Matsumoto, Nukhet Aykin-Burns, Douglas R Spitz, Junko Oshima, …

American journal of respiratory and critical care medicine, Vol.179(4), pp.279-287

02/15/2009

DOI: 10.1164/rccm.200802-320OC

PMCID: PMC2643077

PMID: 19011155

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Abstract

Rationale : Werner's syndrome is a genetic disorder that causes premature aging due to loss-of-function mutations in a gene encoding a member of the RecQ helicase family. Both Werner's syndrome and cigarette smoking accelerate aging. No studies have examined the effect of cigarette smoke on Werner's syndrome protein. Objectives : To investigate the role of Werner's syndrome protein in cigarette smoke–induced cellular senescence. Methods : Cellular senescence and amounts of Werner's syndrome protein were measured in fibroblasts isolated from patients with emphysema and compared with age-matched nonsmokers. The in vitro effects of cigarette smoke on amounts of Werner's syndrome protein, function, and senescence were also evaluated in primary human lung fibroblasts and epithelial cells. Measurements and Main Results : Cultured lung fibroblasts isolated from patients with emphysema exhibited a senescent phenotype accompanied by a decrease in Werner's syndrome protein. Cigarette smoke extract decreased Werner's syndrome protein in cultured fibroblasts and epithelial cells. Werner's syndrome protein–deficient fibroblasts were more susceptible to cigarette smoke–induced cellular senescence and cell migration impairment. In contrast, exogenous overexpression of Werner's syndrome protein attenuated the cigarette smoke effects. Conclusions : Cigarette smoke induces cellular senescence and cell migration impairment via Werner's syndrome protein down-regulation. Rescue of Werner's syndrome protein down-regulation may represent a potential therapeutic target for smoking-related diseases.

cell migration

aging

B. Chronic Obstructive Pulmonary Disease

oxidative stress

smoking

emphysema

Details

Title: Subtitle: Cigarette Smoke Induces Cellular Senescence via Werner's Syndrome Protein Down-regulation
Creators: Toru Nyunoya - Department of Pathology, University of Washington, Seattle, Washington
Martha M Monick - Department of Pathology, University of Washington, Seattle, Washington
Aloysius L Klingelhutz - Department of Pathology, University of Washington, Seattle, Washington
Heather Glaser - Department of Pathology, University of Washington, Seattle, Washington
Jeffrey R Cagley - Department of Pathology, University of Washington, Seattle, Washington
Charles O Brown - Department of Pathology, University of Washington, Seattle, Washington
Eiyu Matsumoto - Department of Pathology, University of Washington, Seattle, Washington
Nukhet Aykin-Burns - Department of Pathology, University of Washington, Seattle, Washington
Douglas R Spitz - Department of Pathology, University of Washington, Seattle, Washington
Junko Oshima - Department of Pathology, University of Washington, Seattle, Washington
Gary W Hunninghake - Department of Pathology, University of Washington, Seattle, Washington
Resource Type: Journal article
Publication Details: American journal of respiratory and critical care medicine, Vol.179(4), pp.279-287
DOI: 10.1164/rccm.200802-320OC
PMID: 19011155
PMCID: PMC2643077
NLM abbreviation: Am J Respir Crit Care Med
ISSN: 1073-449X
eISSN: 1535-4970
Publisher: American Thoracic Society
Language: English
Date published: 02/15/2009
Academic Unit: Microbiology and Immunology; Pathology; Radiation Oncology; Internal Medicine
Record Identifier: 9984001219102771

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