Journal article
Acrolein-Exposed Normal Human Lung Fibroblasts in Vitro : Cellular Senescence, Enhanced Telomere Erosion, and Degradation of Werner’s Syndrome Protein
Environmental health perspectives, Vol.122(9), pp.955-962
09/2014
DOI: 10.1289/ehp.1306911
PMCID: PMC4154210
PMID: 24747221
Abstract
Background: Acrolein is a ubiquitous environmental hazard to human health. Acrolein has been reported to activate the DNA damage response and induce apoptosis. However, little is known about the effects of acrolein on cellular senescence.
Objectives: We examined 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. The knockdown of p53 mediated by small interfering RNA (siRNA) attenuated acrolein-induced cellular senescence. Acrolein decreased Werner’s syndrome protein (WRN), a member of the RecQ helicase family involved in DNA repair and telomere maintenance. Acrolein-induced down-regulation of WRN protein was rescued by p53 knockdown or proteasome inhibition. Finally, we found that acrolein accelerated p53-mediated telomere shortening.
Conclusions: These results suggest that acrolein induces p53-mediated cellular senescence accompanied by enhanced telomere attrition and WRN protein down-regulation.
Details
- Title: Subtitle
- Acrolein-Exposed Normal Human Lung Fibroblasts in Vitro : Cellular Senescence, Enhanced Telomere Erosion, and Degradation of Werner’s Syndrome Protein
- Creators
- Jun-Ho Jang - Division of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, University of New Mexico and New Mexico VA Health Care System, Albuquerque, New Mexico, USA, Lovelace Respiratory Research Institute, Albuquerque, New Mexico, USAShannon Bruse - Lovelace Respiratory Research Institute, Albuquerque, New Mexico, USASalam Huneidi - Division of Pulmonary, Critical Care, and Occupational Medicine, andRonald M Schrader - Division of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, University of New Mexico and New Mexico VA Health Care System, Albuquerque, New Mexico, USAMartha M Monick - Division of Pulmonary, Critical Care, and Occupational Medicine, andYong Lin - Lovelace Respiratory Research Institute, Albuquerque, New Mexico, USAA. Brent Carter - Division of Pulmonary, Critical Care, and Occupational Medicine, andAloysius J Klingelhutz - Department of Microbiology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa, USAToru Nyunoya - Division of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, University of New Mexico and New Mexico VA Health Care System, Albuquerque, New Mexico, USA, Lovelace Respiratory Research Institute, Albuquerque, New Mexico, USA
- Resource Type
- Journal article
- Publication Details
- Environmental health perspectives, Vol.122(9), pp.955-962
- DOI
- 10.1289/ehp.1306911
- PMID
- 24747221
- PMCID
- PMC4154210
- ISSN
- 0091-6765
- eISSN
- 1552-9924
- Language
- English
- Date published
- 09/2014
- Academic Unit
- Microbiology and Immunology; Radiation Oncology; Internal Medicine
- Record Identifier
- 9984001230302771
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