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.

Reactive aldehyde-scavenging enzyme activities in atherosclerotic plaques of cigarette smokers and nonsmokers

“…It has recently been reported that ALDH3A1 is induced in bronchial epithelial cells by CS extract exposure in vitro [16]. To reconcile this experimental finding with the results of our study showing a depressed plaque ALDH activity in cigarette smokers, it should be considered that vascular antioxidant enzymes reportedly undergo an early prelesional induction and then a decreased expression in atherosclerotic lesions in vivo [17].…”

“…To reconcile this experimental finding with the results of our study showing a depressed plaque ALDH activity in cigarette smokers, it should be considered that vascular antioxidant enzymes reportedly undergo an early prelesional induction and then a decreased expression in atherosclerotic lesions in vivo [17]. Moreover, various cell types may respond differently to noxious conditions including cigarette smoking [16]; indeed, while activated in bronchial epithelial cells [16], ALDH is instead inactivated by CS components in human blood cells as shown by Helander et al [18]. This latter finding is consistent with our results showing a depressed ALDH activity in human atherosclerotic lesions, where also blood cells are present.…”

Connective Tissue Growth Factor Promotes Pulmonary Epithelial Cell Senescence and Is Associated with COPD Severity

“…UNCN3T cells were transduced with a lentiviral vector (cat#EX-A0312-LV152, pReceiver, GeneCopoeia, Rockville, MD) to overexpress CTGF protein as previously described (30). The transduced cells were selected with 5 µg/ml hygromycin for 14 days and surviving cells were collected.…”

“…CTGF-overexpressing or the control cells were cultured in p100 plates (100 mm) at a starting cell density of 15 × 10 3 /cm 2 and harvested after 3 d. Cell lysates were prepared in RIPA buffer with protease inhibitors (Boehringer Mannheim, Ridgefield, CT) and analyzed by immunoblotting as previously described (30). Protein levels were evaluated using anti-CTGF, anti-p53 antibody (Santa Cruz, CA) or anti-p16 and anti-p21 antibodies (Abcam, Cambridge, MA), and equal loading of protein samples from each group was evaluated using anti-β actin antibody (Sigma-Aldrich) after using the Restore WB stripping buffer (Thermo Fisher Scientific, Barrington, IL).…”

The Effect of Ambient Ozone on Unsaturated Tear Film Wax Esters

“…3 Rapid removal of aldehydes is essential to maintain the health of epithelial cells. 4 Tear film bears many similarities with lung-lining fluid of the alveoli, as these two structures are the only air-water interfaces in the human body. 5 Being in constant contact with surrounding air, tear film is also subject to similar ozone stress as the alveolar fluid, and therefore it is possible that increased ozone exposure may lead to ocular irritation through a similar mechanism.…”