Research Advance Publication
Acrolein-Exposed Normal Human Lung Fibroblasts in Vitro: Cellular Senescence, Enhanced Telomere Erosion, and Degradation of Werner’s Syndrome Protein
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Citation: Jang JH, Bruse S, Huneidi S, Schrader RM, Monick MM, Lin Y, Carter AB, Klingelhutz AJ, Nyunoya T. Acrolein-Exposed Normal Human Lung Fibroblasts in Vitro: Cellular Senescence, Enhanced Telomere Erosion, and Degradation of Werner’s Syndrome Protein. Environ Health Perspect; http://dx.doi.org/10.1289/ehp.1306911.
Received: 8 April 2013
Accepted: 15 April 2014
Advance Publication: 18 April 2014
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Background: Acrolein is a carcinogenic and ubiquitous environmental hazard to human health. Acrolein activates the DNA damage response and induces apoptosis. However, little is known about the effects of acrolein on cellular senescence.
Objectives: In this study, we investigated whether acrolein induces cellular senescence in cultured normal human lung fibroblasts (NHLF).
Methods: We cultured NHLF in the presence or absence of acrolein and determined the effects of acrolein on cell proliferative capacity, senescence-associated β-galactosidase activity, the known senescence-inducing pathways (e.g., p53-p21), and telomere length.
Results: We found that acrolein induced cellular senescence by increasing both p53 and p21. siRNA-mediated knockdown of p53 attenuated acrolein-induced cellular senescence. Acrolein decreased Werner’s syndrome protein (WRN protein), a member of the RecQ helicase family involved in DNA repair and telomere maintenance. Acrolein-induced downregulation of WRN protein was rescued by p53 knockdown or proteasome inhibition. Finally, we found that acrolein accelerates p53-mediated telomere shortening.
Conclusions: These results suggest that acrolein induces p53-mediated cellular senescence accompanied by enhanced telomere attrition and WRN protein downregulation.
CEHN July 2014 Article of the Month
“Outdoor Formaldehyde and NO2 Exposures and Markers of Genotoxicity in Children Living Near Chipboard Industries” (Environ Health Perspect; DOI:10.1289/ehp.1307259) has been selected by the Children’s Environmental Health Network (CEHN) as its July 2014 Article of the Month. These CEHN summaries discuss the potential policy implications of current children’s environmental health research.
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