title: Acrolein-exposed normal human lung fibroblasts in vitro: cellular senescence, enhanced telomere erosion, and degradation of Werner's syndrome protein.
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.
  
  
  OBJECTIVE
  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.
authors.affiliation: 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.
authors.forename: Jun-Ho
authors.initials: JH
authors.lastname: Jang
authors.forename: Shannon
authors.initials: S
authors.lastname: Bruse
authors.forename: Salam
authors.initials: S
authors.lastname: Huneidi
authors.forename: Ronald M
authors.initials: RM
authors.lastname: Schrader
authors.forename: Martha M
authors.initials: MM
authors.lastname: Monick
authors.forename: Yong
authors.initials: Y
authors.lastname: Lin
authors.forename: A Brent
authors.initials: AB
authors.lastname: Carter
authors.forename: Aloysius J
authors.initials: AJ
authors.lastname: Klingelhutz
authors.forename: Toru
authors.initials: T
authors.lastname: Nyunoya
mesh_terms: D000171:Acrolein / Q000633:toxicity*; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000187:drug effects*; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D004260:DNA Repair / Q000187:drug effects; D015536:Down-Regulation; D004785:Environmental Pollutants / Q000633:toxicity*; D005090:Exodeoxyribonucleases / Q000378:metabolism*; D005347:Fibroblasts / Q000187:drug effects*; D006801:Humans; D008168:Lung / Q000166:cytology / Q000378:metabolism; D053484:RecQ Helicases / Q000378:metabolism*; D016615:Telomere / Q000187:drug effects* / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D000071657:Werner Syndrome Helicase; D001616:beta-Galactosidase / Q000378:metabolism
chemical_list: D050759:Cyclin-Dependent Kinase Inhibitor p21; D004785:Environmental Pollutants; D016159:Tumor Suppressor Protein p53; D000171:Acrolein; D005090:Exodeoxyribonucleases; D001616:beta-Galactosidase; D053484:RecQ Helicases; C098785:WRN protein, human; D000071657:Werner Syndrome Helicase
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