Mitochondrial aldehyde dehydrogenase 2 protects gastric mucosa cells against DNA damage caused by oxidative stress

• Published in: Free radical biology & medicine Vol. 93; pp. 165 - 176
• Main Authors: Duan, Yantao, Gao, Yaohui, Zhang, Jun, Chen, Yinan, Jiang, Yannan, Ji, Jun, Zhang, Jianian, Chen, Xuehua, Yang, Qiumeng, Su, Liping, Liu, Bingya, Zhu, Zhenggang, Wang, Lishun, Yu, Yingyan
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.04.2016
• Subjects: 4-Hydroxynonenal; Aldehyde Dehydrogenase, Mitochondrial - genetics; Aldehyde Dehydrogenase, Mitochondrial - metabolism; Aldehydes - metabolism; ALDH2; Apoptosis; Apoptosis - drug effects; Cell Line; Cell Survival - drug effects; DNA damage; DNA Damage - drug effects; Gastric Mucosa - enzymology; Humans; Hydrogen Peroxide - pharmacology; Mitochondria - drug effects; Mitochondria - enzymology; Oxidative stress; Oxidative Stress - genetics; Oxidative stress; ALDH2; 4-Hydroxynonenal; DNA damage; Apoptosis
• ISSN: 0891-5849; 1873-4596
• DOI: 10.1016/j.freeradbiomed.2016.02.001

Mitochondrial aldehyde dehydrogenase 2 (ALDH2) is a member of the aldehyde dehydrogenase superfamily and is involved with the metabolic processing of aldehydes. ALDH2 plays a cytoprotective role by removing aldehydes produced during normal metabolism. We examined the cytoprotective role of ALDH2 specifically in gastric mucosa cells. Overexpression of ALDH2 increased the viability of gastric mucosa cells treated with H2O2, while knockdown of ALDH2 had an opposite effect. Moreover, overexpression of ALDH2 protected gastric mucosa cells against oxidative stress-induced apoptosis as determined by flow cytometry, Hoechst 33342, and TUNEL assays. Consistently, ALDH2 knockdown had an opposite effect. Additionally, DNA damage was ameliorated in ALDH2-overexpressing gastric mucosa cells treated with H2O2. We further identified that this cytoprotective role of ALDH2 was mediated by metabolism of 4-hydroxynonenal (4-HNE). Consistently, 4-HNE mimicked the oxidative stress induced by H2O2 in gastric mucosa cells. Treatment with 4-HNE increased levels of DNA damage in ALDH2-knockdown GES-1 cells, while overexpression of ALDH2 decreased 4-HNE-induced DNA damage. These findings suggest that ALDH2 can protect gastric mucosa cells against DNA damage caused by oxidative stress by reducing levels of 4-HNE. [Display omitted] •ALDH2 reduces oxidative stress-induced cytotoxicity in gastric mucosa cells.•ALDH2 reduces oxidative stress-induced apoptosis.•ALDH2 protects against oxidative stress-induced DNA damage.•ALDH2 metabolizes 4-HNE.