Статья

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

Yantao DuanDepartment 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 ChinaYaohui GaoLab. of Translational Medicine, Minhang Hospital, Fudan University, No. 170 Xinsong Road, Shanghai 201199, People's Republic of ChinaJun ZhangDepartment 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 ChinaYinan ChenDepartment 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 ChinaYannan JiangDepartment 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 ChinaJun JiDepartment 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 ChinaJianian ZhangDepartment 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 ChinaXuehua ChenDepartment 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 ChinaQiumeng YangDepartment 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 ChinaLiping SuDepartment 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 ChinaBingya LiuDepartment 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 ChinaZhenggang ZhuDepartment 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 ChinaLi‐Shun WangLab. of Translational Medicine, Minhang Hospital, Fudan University, No. 170 Xinsong Road, Shanghai 201199, People's Republic of China. Electronic address: [email protected]Yingyan YuDepartment 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: [email protected]

2016en

ABI

Аннотация

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.

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Идентификаторы

DOI: 10.1016/j.freeradbiomed.2016.02.001

Цитирования и источники

Цитирований: 2Использованных источников: 0

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