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

• Published in: Biochemical and biophysical research communications Vol. 504; no. 4; pp. 777 - 783
• Main Authors: Xue, Li, Yang, Feihong, Han, Ziqi, Cui, Sumei, Dai, Shuai, Xu, Feng, Zhang, Chuanxin, Wang, Xuping, Pang, Jiaojiao, Pan, Chang, Chen, Yuguo
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 12.10.2018
• Subjects: 4-HNE; 60 APPLIED LIFE SCIENCES; ACETYLATION; ALDEHYDES; ALDH2; CYTOPLASM; Endothelial senescence; eNOS; ETHANOL; OXIDOREDUCTASES; PHENOTYPE; SIRT1; eNOS; Ethanol; ALDH2; 4-HNE; SIRT1; Endothelial senescence
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2018.08.081

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. •Chronic ethanol exerts dose-response protection against endothelial senescence.•Chronic appropriate dose of ethanol upregulates ALDH2 expression and activity.•ALDH2 deficiency inhibits ethanol protection by producing 4-HNE-SIRT1 adducts.•4-HNE-SIRT1 blocks the translocation of SIRT1 from the cytoplasm to the nucleus.•Cytoplasmic SIRT1 promotes endothelial senescence by increasing p53 acetylation.