Acrolein-exposed normal human lung fibroblasts in vitro: cellular senescence, enhanced telomere erosion, and degradation of Werner's syndrome protein

Environ Health Perspect. 2014 Sep;122(9):955-62. doi: 10.1289/ehp.1306911. Epub 2014 Apr 18.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Acrolein / toxicity*
  • Cells, Cultured
  • Cellular Senescence / drug effects*
  • Cyclin-Dependent Kinase Inhibitor p21 / metabolism
  • DNA Repair / drug effects
  • Down-Regulation
  • Environmental Pollutants / toxicity*
  • Exodeoxyribonucleases / metabolism*
  • Fibroblasts / drug effects*
  • Humans
  • Lung / cytology
  • Lung / metabolism
  • RecQ Helicases / metabolism*
  • Telomere / drug effects*
  • Telomere / metabolism
  • Tumor Suppressor Protein p53 / metabolism
  • Werner Syndrome Helicase
  • beta-Galactosidase / metabolism


  • Cyclin-Dependent Kinase Inhibitor p21
  • Environmental Pollutants
  • Tumor Suppressor Protein p53
  • Acrolein
  • Exodeoxyribonucleases
  • beta-Galactosidase
  • RecQ Helicases
  • WRN protein, human
  • Werner Syndrome Helicase