Open AccessAlda-1 Ameliorates Liver Ischemia-Reperfusion Injury by Activating Aldehyde Dehydrogenase 2 and Enhancing Autophagy in Mice
Author(s) -
Meng Li,
Min Xu,
Jichang Li,
Lili Chen,
Dongwei Xu,
Ying Tong,
Jianjun Zhang,
Hailong Wu,
Xiaoni Kong,
Qiang Xia
Publication year - 2018
Publication title -
journal of immunology research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.315
H-Index - 83
eISSN - 2314-8861
pISSN - 2314-7156
DOI - 10.1155/2018/9807139
Subject(s) - aldh2 , aldehyde dehydrogenase , autophagy , ampk , reperfusion injury , liver injury , ischemia , chemistry , activator (genetics) , pharmacology , biochemistry , hepatocyte , enzyme , apoptosis , medicine , protein kinase a , gene , in vitro
Aldehyde dehydrogenase 2 (ALDH2) is a key enzyme for metabolism of reactive aldehydes, but its role during liver ischemia-reperfusion injury (IRI) remains unclear. In the present study, we investigated the effects of the ALDH2 activator, Alda-1, in liver IRI and elucidated the underlying mechanisms. Mice were pretreated with Alda-1 and subjected to a 90 min hepatic 70% ischemia model, and liver tissues or serum samples were collected at indicated time points after reperfusion. We demonstrated that Alda-1 pretreatment had a hepatoprotective role in liver IRI as evidenced by decreased liver necrotic areas, serum ALT/AST levels, and liver inflammatory responses. Mechanistically, Alda-1 treatment enhanced ALDH2 activity and subsequently reduced the accumulation of reactive aldehydes and toxic protein adducts, which result in decreased hepatocyte apoptosis and mitochondrial dysfunction. We further demonstrated that Alda-1 treatment could activate AMPK and autophagy and that AMPK activation was required for Alda-1-mediated autophagy enhancement. These findings collectively indicate that Alda-1-mediated ALDH2 activation could be a promising strategy to improve liver IRI by clearance of reactive aldehydes and enhancement of autophagy.