title: Aldehyde dehydrogenase 3A1 protects airway epithelial cells from cigarette smoke-induced DNA damage and cytotoxicity.
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.
authors: Division of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, University of New Mexico, Albuquerque, NM 87131, USA; New Mexico VA Health Care System, Albuquerque, NM 87108, USA; COPD Program, Lovelace Respiratory Research Institute, Albuquerque, NM 87108, USA.
authors: Jun-Ho
authors: JH
authors: Jang
authors: COPD Program, Lovelace Respiratory Research Institute, Albuquerque, NM 87108, USA.
authors: Shannon
authors: S
authors: Bruse
authors: COPD Program, Lovelace Respiratory Research Institute, Albuquerque, NM 87108, USA.
authors: Yushi
authors: Y
authors: Liu
authors: COPD Program, Lovelace Respiratory Research Institute, Albuquerque, NM 87108, USA.
authors: Veronica
authors: V
authors: Duffy
authors: COPD Program, Lovelace Respiratory Research Institute, Albuquerque, NM 87108, USA.
authors: Chunyu
authors: C
authors: Zhang
authors: COPD Program, Lovelace Respiratory Research Institute, Albuquerque, NM 87108, USA.
authors: Nathaniel
authors: N
authors: Oyamada
authors: Department of Cell and Molecular Physiology, University of North Carolina, Chapel Hill, NC 27599, USA.
authors: Scott
authors: S
authors: Randell
authors: Department of Pharmacology, University of Colorado at Denver, Aurora, CO 80045, USA.
authors: Akiko
authors: A
authors: Matsumoto
authors: Department of Pharmacology, University of Colorado at Denver, Aurora, CO 80045, USA.
authors: David C
authors: DC
authors: Thompson
authors: COPD Program, Lovelace Respiratory Research Institute, Albuquerque, NM 87108, USA.
authors: Yong
authors: Y
authors: Lin
authors: Department of Pharmacology, University of Colorado at Denver, Aurora, CO 80045, USA.
authors: Vasilis
authors: V
authors: Vasiliou
authors: COPD Program, Lovelace Respiratory Research Institute, Albuquerque, NM 87108, USA.
authors: Yohannes
authors: Y
authors: Tesfaigzi
authors: Division of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, University of New Mexico, Albuquerque, NM 87131, USA; New Mexico VA Health Care System, Albuquerque, NM 87108, USA; COPD Program, Lovelace Respiratory Research Institute, Albuquerque, NM 87108, USA. Electronic address: tnyunoya@lrri.org.
authors: Toru
authors: T
authors: Nyunoya
mesh_terms: D000444:Aldehyde Dehydrogenase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000447:Aldehydes / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D001980:Bronchi / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004249:DNA Damage / Q000187:drug effects / Q000235:genetics; D004847:Epithelial Cells / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D006801:Humans; D034741:RNA, Small Interfering; D012907:Smoking / Q000009:adverse effects*
chemical_list: D000447:Aldehydes; D034741:RNA, Small Interfering; C480021:ALDH3A1 protein, human; D000444:Aldehyde Dehydrogenase
keywords: ALDH3A1; Airway epithelial cells; Chronic obstructive pulmonary disease; Cigarette smoke; Cytotoxicity; DNA damage; FANCD2; Free radicals; Reactive aldehydes