title: Mitochondrial aldehyde dehydrogenase 2 protects gastric mucosa cells against DNA damage caused by oxidative stress.
abstract: 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.
authors: Department of Surgery, Ruijin Hospital, Shanghai Institute of Digestive Surgery and Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Jiao Tong University School of Medicine, No. 197 Ruijin er Road, Shanghai 200025, People's Republic of China.
authors: Yantao
authors: Y
authors: Duan
authors: Lab. of Translational Medicine, Minhang Hospital, Fudan University, No. 170 Xinsong Road, Shanghai 201199, People's Republic of China.
authors: Yaohui
authors: Y
authors: Gao
authors: Department of Surgery, Ruijin Hospital, Shanghai Institute of Digestive Surgery and Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Jiao Tong University School of Medicine, No. 197 Ruijin er Road, Shanghai 200025, People's Republic of China.
authors: Jun
authors: J
authors: Zhang
authors: Department of Surgery, Ruijin Hospital, Shanghai Institute of Digestive Surgery and Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Jiao Tong University School of Medicine, No. 197 Ruijin er Road, Shanghai 200025, People's Republic of China.
authors: Yinan
authors: Y
authors: Chen
authors: Department of Surgery, Ruijin Hospital, Shanghai Institute of Digestive Surgery and Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Jiao Tong University School of Medicine, No. 197 Ruijin er Road, Shanghai 200025, People's Republic of China.
authors: Yannan
authors: Y
authors: Jiang
authors: Department of Surgery, Ruijin Hospital, Shanghai Institute of Digestive Surgery and Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Jiao Tong University School of Medicine, No. 197 Ruijin er Road, Shanghai 200025, People's Republic of China.
authors: Jun
authors: J
authors: Ji
authors: Department of Surgery, Ruijin Hospital, Shanghai Institute of Digestive Surgery and Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Jiao Tong University School of Medicine, No. 197 Ruijin er Road, Shanghai 200025, People's Republic of China.
authors: Jianian
authors: J
authors: Zhang
authors: Department of Surgery, Ruijin Hospital, Shanghai Institute of Digestive Surgery and Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Jiao Tong University School of Medicine, No. 197 Ruijin er Road, Shanghai 200025, People's Republic of China.
authors: Xuehua
authors: X
authors: Chen
authors: Department of Surgery, Ruijin Hospital, Shanghai Institute of Digestive Surgery and Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Jiao Tong University School of Medicine, No. 197 Ruijin er Road, Shanghai 200025, People's Republic of China.
authors: Qiumeng
authors: Q
authors: Yang
authors: Department of Surgery, Ruijin Hospital, Shanghai Institute of Digestive Surgery and Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Jiao Tong University School of Medicine, No. 197 Ruijin er Road, Shanghai 200025, People's Republic of China.
authors: Liping
authors: L
authors: Su
authors: Department of Surgery, Ruijin Hospital, Shanghai Institute of Digestive Surgery and Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Jiao Tong University School of Medicine, No. 197 Ruijin er Road, Shanghai 200025, People's Republic of China.
authors: Jun
authors: J
authors: Zhang
authors: Department of Surgery, Ruijin Hospital, Shanghai Institute of Digestive Surgery and Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Jiao Tong University School of Medicine, No. 197 Ruijin er Road, Shanghai 200025, People's Republic of China.
authors: Bingya
authors: B
authors: Liu
authors: Department of Surgery, Ruijin Hospital, Shanghai Institute of Digestive Surgery and Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Jiao Tong University School of Medicine, No. 197 Ruijin er Road, Shanghai 200025, People's Republic of China; Collaborative Innovation Center of Systems Biomedicine, Shanghai Jiao Tong University, Shanghai 200025, People's Republic of China.
authors: Zhenggang
authors: Z
authors: Zhu
authors: Lab. of Translational Medicine, Minhang Hospital, Fudan University, No. 170 Xinsong Road, Shanghai 201199, People's Republic of China. Electronic address: lishunwang@fudan.edu.cn.
authors: Lishun
authors: L
authors: Wang
authors: Department of Surgery, Ruijin Hospital, Shanghai Institute of Digestive Surgery and Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Jiao Tong University School of Medicine, No. 197 Ruijin er Road, Shanghai 200025, People's Republic of China; Collaborative Innovation Center of Systems Biomedicine, Shanghai Jiao Tong University, Shanghai 200025, People's Republic of China. Electronic address: yingyan3y@sjtu.edu.cn.
authors: Yingyan
authors: Y
authors: Yu
mesh_terms: D000071396:Aldehyde Dehydrogenase, Mitochondrial / Q000235:genetics* / Q000378:metabolism; D000447:Aldehydes / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004249:DNA Damage / Q000187:drug effects*; D005753:Gastric Mucosa / Q000201:enzymology*; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008928:Mitochondria / Q000187:drug effects / Q000201:enzymology; D018384:Oxidative Stress / Q000235:genetics*
chemical_list: D000447:Aldehydes; D006861:Hydrogen Peroxide; C096127:ALDH2 protein, human; D000071396:Aldehyde Dehydrogenase, Mitochondrial; C027576:4-hydroxy-2-nonenal
keywords: 4-Hydroxynonenal; ALDH2; Apoptosis; DNA damage; Oxidative stress