ALDH2 mediates the dose-response protection of chronic ethanol against endothelial senescence through SIRT1/p53 pathway

Li Xue; Feihong Yang; Ziqi Han; Sumei Cui; Shuai Dai; Feng Xu; Chuanxin Zhang; Xuping Wang; Jiaojiao Pang; Chang Pan; Yuguo Chen

doi:10.1016/j.bbrc.2018.08.081

ALDH2 mediates the dose-response protection of chronic ethanol against endothelial senescence through SIRT1/p53 pathway

Biochem Biophys Res Commun. 2018 Oct 12;504(4):777-783. doi: 10.1016/j.bbrc.2018.08.081. Epub 2018 Sep 11.

Authors

Li Xue¹, Feihong Yang², Ziqi Han¹, Sumei Cui¹, Shuai Dai¹, Feng Xu¹, Chuanxin Zhang¹, Xuping Wang³, Jiaojiao Pang¹, Chang Pan¹, Yuguo Chen⁴

Affiliations

¹ Department of Emergency Medicine and Chest Pain Center, Qilu Hospital of Shandong University, Jinan, China; Clinical Research Center for Emergency and Critical Care Medicine of Shandong Province, Institute of Emergency and Critical Care Medicine of Shandong University, Qilu Hospital of Shandong University, Jinan, China; Key Laboratory of Emergency and Critical Care Medicine of Shandong Province, Key Laboratory of Cardiopulmonary-Cerebral Resuscitation Research of Shandong Province, Qilu Hospital of Shandong University, Jinan, China; Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese Ministry of Health and Chinese Academy of Medical Sciences, State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Qilu Hospital of Shandong University, Jinan, China.
² Department of Emergency Medicine and Chest Pain Center, Qilu Hospital of Shandong University, Jinan, China; Clinical Research Center for Emergency and Critical Care Medicine of Shandong Province, Institute of Emergency and Critical Care Medicine of Shandong University, Qilu Hospital of Shandong University, Jinan, China; Key Laboratory of Emergency and Critical Care Medicine of Shandong Province, Key Laboratory of Cardiopulmonary-Cerebral Resuscitation Research of Shandong Province, Qilu Hospital of Shandong University, Jinan, China; Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese Ministry of Health and Chinese Academy of Medical Sciences, State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Qilu Hospital of Shandong University, Jinan, China; Emergency Center, Zhongnan Hospital of Wuhan University, Wuhan, China.
³ Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese Ministry of Health and Chinese Academy of Medical Sciences, State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Qilu Hospital of Shandong University, Jinan, China.
⁴ Department of Emergency Medicine and Chest Pain Center, Qilu Hospital of Shandong University, Jinan, China; Clinical Research Center for Emergency and Critical Care Medicine of Shandong Province, Institute of Emergency and Critical Care Medicine of Shandong University, Qilu Hospital of Shandong University, Jinan, China; Key Laboratory of Emergency and Critical Care Medicine of Shandong Province, Key Laboratory of Cardiopulmonary-Cerebral Resuscitation Research of Shandong Province, Qilu Hospital of Shandong University, Jinan, China; Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese Ministry of Health and Chinese Academy of Medical Sciences, State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Qilu Hospital of Shandong University, Jinan, China. Electronic address: chen919085@sdu.edu.cn.

PMID: 30217444
DOI: 10.1016/j.bbrc.2018.08.081

Abstract

Aldehyde dehydrogenase 2 (ALDH2) plays essential roles in drinking-associated diseases or effects. As we have previously reported, ALDH2 mediates acute ethanol-induced eNOS activation in vitro. However, whether chronic ethanol treatment has a dose-response endothelial protection, as well as the possible mediating role of ALDH2 involved, is unclear. Here, we show that appropriate dose of ethanol preserved the expression and activity of ALDH2 and eNOS, and alleviated senescence-associated phenotypes in human aortic endothelial cells. Furthermore, ALDH2 deficiency impairs the dose-response protection of ethanol against endothelial senescence by promoting the accumulation of 4-HNE, the formation of 4-HNE-SIRT1 protein adducts and the subsequent decrease in SIRT1-dependent p53 deacetylation. Collectively, our data indicate that ALDH2 mediates the protection of appropriate ethanol by modulating SIRT1/p53-dependent endothelial senescence.

Keywords: 4-HNE; ALDH2; Endothelial senescence; Ethanol; SIRT1; eNOS.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Acetylation
Aldehyde Dehydrogenase, Mitochondrial / genetics
Aldehyde Dehydrogenase, Mitochondrial / metabolism*
Aorta / cytology
Cells, Cultured
Cellular Senescence
Dose-Response Relationship, Drug
Endothelial Cells / drug effects*
Endothelial Cells / metabolism
Endothelial Cells / pathology
Ethanol / toxicity*
Humans
Nitric Oxide Synthase Type III / genetics
Nitric Oxide Synthase Type III / metabolism
Protein Transport / drug effects
Reactive Oxygen Species / metabolism
Sirtuin 1 / genetics
Sirtuin 1 / metabolism*
Toxicity Tests, Chronic
Tumor Suppressor Protein p53 / metabolism*

Substances

Reactive Oxygen Species
TP53 protein, human
Tumor Suppressor Protein p53
Ethanol
NOS3 protein, human
Nitric Oxide Synthase Type III
ALDH2 protein, human
Aldehyde Dehydrogenase, Mitochondrial
SIRT1 protein, human
Sirtuin 1