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

被引：25

作者：

Duan, Yantao ^{[1
,2
]}

Gao, Yaohui ^{[3
]}

Zhang, Jun ^{[1
,2
]}

Chen, Yinan ^{[1
,2
]}

Jiang, Yannan ^{[1
,2
]}

Ji, Jun ^{[1
,2
]}

Zhang, Jianian ^{[1
,2
]}

Chen, Xuehua ^{[1
,2
]}

Yang, Qiumeng ^{[1
,2
]}

Su, Liping ^{[1
,2
]}

Zhang, Jun ^{[1
,2
]}

Liu, Bingya ^{[1
,2
]}

Zhu, Zhenggang ^{[1
,2
,4
]}

Wang, Lishun ^{[3
]}

Yu, Yingyan ^{[1
,2
,4
]}

机构：

[1] Shanghai Jiao Tong Univ, Sch Med, Shanghai Inst Digest Surg, Dept Surg,Ruijin Hosp, 197 Ruijin Er Rd, Shanghai 200025, Peoples R China

[2] Shanghai Jiao Tong Univ, Sch Med, Shanghai Key Lab Gastr Neoplasms, 197 Ruijin Er Rd, Shanghai 200025, Peoples R China

[3] Fudan Univ, Minhang Hosp, Lab Translat Med, 170 Xinsong Rd, Shanghai 201199, Peoples R China

[4] Shanghai Jiao Tong Univ, Collaborat Innovat Ctr Syst Biomed, Shanghai 200025, Peoples R China

来源：

FREE RADICAL BIOLOGY AND MEDICINE | 2016年 / 93卷

基金：

中国国家自然科学基金;

关键词：

ALDH2; Oxidative stress; DNA damage; Apoptosis; 4-Hydroxynonenal; LIPID-PEROXIDATION; HELICOBACTER-PYLORI; CANCER; ALDH2; SPECIFICITY; HOMEOSTASIS; PROGRESSION; INHIBITION; ACTIVATION; APOPTOSIS;

D O I：

10.1016/j.freeradbiomed.2016.02.001

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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. (C) 2016 The Authors. Published by Elsevier Inc.

引用

页码：165 / 176

页数：12

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