Aldehyde dehydrogenase 3A1 protects airway epithelial cells from cigarette smoke-induced DNA damage and cytotoxicity

Free Radic Biol Med. 2014 Mar;68:80-6. doi: 10.1016/j.freeradbiomed.2013.11.028. Epub 2013 Dec 4.

Abstract

Aldehyde dehydrogenase 3A1 (ALDH3A1), an ALDH superfamily member, catalyzes the oxidation of reactive aldehydes, highly toxic components of cigarette smoke (CS). Even so, the role of ALDH3A1 in CS-induced cytotoxicity and DNA damage has not been examined. Among all of the ALDH superfamily members, ALDH3A1 mRNA levels showed the greatest induction in response to CS extract (CSE) exposure of primary human bronchial epithelial cells (HBECs). ALDH3A1 protein accumulation was accompanied by increased ALDH enzymatic activity in CSE-exposed immortalized HBECs. The effects of overexpression or suppression of ALDH3A1 on CSE-induced cytotoxicity and DNA damage (γH2AX) were evaluated in cultured immortalized HBECs. Enforced expression of ALDH3A1 attenuated cytotoxicity and downregulated γH2AX. SiRNA-mediated suppression of ALDH3A1 blocked ALDH enzymatic activity and augmented cytotoxicity in CSE-exposed cells. Our results suggest that the availability of ALDH3A1 is important for cell survival against CSE in HBECs.

Keywords: ALDH3A1; Airway epithelial cells; Chronic obstructive pulmonary disease; Cigarette smoke; Cytotoxicity; DNA damage; FANCD2; Free radicals; Reactive aldehydes.

Publication types

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

MeSH terms

  • Aldehyde Dehydrogenase / antagonists & inhibitors
  • Aldehyde Dehydrogenase / metabolism*
  • Aldehydes / metabolism
  • Apoptosis / drug effects
  • Bronchi / drug effects
  • Bronchi / enzymology*
  • Bronchi / pathology
  • Cell Survival / drug effects
  • Cells, Cultured
  • DNA Damage / drug effects
  • DNA Damage / genetics
  • Epithelial Cells / drug effects
  • Epithelial Cells / enzymology*
  • Epithelial Cells / metabolism
  • Humans
  • RNA, Small Interfering
  • Smoking / adverse effects*

Substances

  • Aldehydes
  • RNA, Small Interfering
  • ALDH3A1 protein, human
  • Aldehyde Dehydrogenase