Alda-1 Ameliorates Liver Ischemia-Reperfusion Injury by Activating Aldehyde Dehydrogenase 2 and Enhancing Autophagy in Mice
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....
Saved in:
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2018-01-01
|
| Series: | Journal of Immunology Research |
| Online Access: | http://dx.doi.org/10.1155/2018/9807139 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832546129923801088 |
|---|---|
| author | Meng Li Min Xu Jichang Li Lili Chen Dongwei Xu Ying Tong Jianjun Zhang Hailong Wu Xiaoni Kong Qiang Xia |
| author_facet | Meng Li Min Xu Jichang Li Lili Chen Dongwei Xu Ying Tong Jianjun Zhang Hailong Wu Xiaoni Kong Qiang Xia |
| author_sort | Meng Li |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-4fb32cdf9ae4482f954dbbdd60bbfd84 |
| institution | Kabale University |
| issn | 2314-8861 2314-7156 |
| language | English |
| publishDate | 2018-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Immunology Research |
| spelling | doaj-art-4fb32cdf9ae4482f954dbbdd60bbfd842025-02-03T07:23:50ZengWileyJournal of Immunology Research2314-88612314-71562018-01-01201810.1155/2018/98071399807139Alda-1 Ameliorates Liver Ischemia-Reperfusion Injury by Activating Aldehyde Dehydrogenase 2 and Enhancing Autophagy in MiceMeng Li0Min Xu1Jichang Li2Lili Chen3Dongwei Xu4Ying Tong5Jianjun Zhang6Hailong Wu7Xiaoni Kong8Qiang Xia9Department of Liver Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, ChinaDepartment of Liver Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, ChinaDepartment of Liver Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, ChinaDepartment of Liver Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, ChinaDepartment of Liver Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, ChinaDepartment of Liver Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, ChinaDepartment of Liver Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, ChinaShanghai Key Laboratory for Molecular Imaging, Collaborative Research Center, Shanghai University of Medicine & Health Science, Shanghai, ChinaDepartment of Liver Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, ChinaDepartment of Liver Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, ChinaAldehyde 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.http://dx.doi.org/10.1155/2018/9807139 |
| spellingShingle | Meng Li Min Xu Jichang Li Lili Chen Dongwei Xu Ying Tong Jianjun Zhang Hailong Wu Xiaoni Kong Qiang Xia Alda-1 Ameliorates Liver Ischemia-Reperfusion Injury by Activating Aldehyde Dehydrogenase 2 and Enhancing Autophagy in Mice Journal of Immunology Research |
| title | Alda-1 Ameliorates Liver Ischemia-Reperfusion Injury by Activating Aldehyde Dehydrogenase 2 and Enhancing Autophagy in Mice |
| title_full | Alda-1 Ameliorates Liver Ischemia-Reperfusion Injury by Activating Aldehyde Dehydrogenase 2 and Enhancing Autophagy in Mice |
| title_fullStr | Alda-1 Ameliorates Liver Ischemia-Reperfusion Injury by Activating Aldehyde Dehydrogenase 2 and Enhancing Autophagy in Mice |
| title_full_unstemmed | Alda-1 Ameliorates Liver Ischemia-Reperfusion Injury by Activating Aldehyde Dehydrogenase 2 and Enhancing Autophagy in Mice |
| title_short | Alda-1 Ameliorates Liver Ischemia-Reperfusion Injury by Activating Aldehyde Dehydrogenase 2 and Enhancing Autophagy in Mice |
| title_sort | alda 1 ameliorates liver ischemia reperfusion injury by activating aldehyde dehydrogenase 2 and enhancing autophagy in mice |
| url | http://dx.doi.org/10.1155/2018/9807139 |
| work_keys_str_mv | AT mengli alda1amelioratesliverischemiareperfusioninjurybyactivatingaldehydedehydrogenase2andenhancingautophagyinmice AT minxu alda1amelioratesliverischemiareperfusioninjurybyactivatingaldehydedehydrogenase2andenhancingautophagyinmice AT jichangli alda1amelioratesliverischemiareperfusioninjurybyactivatingaldehydedehydrogenase2andenhancingautophagyinmice AT lilichen alda1amelioratesliverischemiareperfusioninjurybyactivatingaldehydedehydrogenase2andenhancingautophagyinmice AT dongweixu alda1amelioratesliverischemiareperfusioninjurybyactivatingaldehydedehydrogenase2andenhancingautophagyinmice AT yingtong alda1amelioratesliverischemiareperfusioninjurybyactivatingaldehydedehydrogenase2andenhancingautophagyinmice AT jianjunzhang alda1amelioratesliverischemiareperfusioninjurybyactivatingaldehydedehydrogenase2andenhancingautophagyinmice AT hailongwu alda1amelioratesliverischemiareperfusioninjurybyactivatingaldehydedehydrogenase2andenhancingautophagyinmice AT xiaonikong alda1amelioratesliverischemiareperfusioninjurybyactivatingaldehydedehydrogenase2andenhancingautophagyinmice AT qiangxia alda1amelioratesliverischemiareperfusioninjurybyactivatingaldehydedehydrogenase2andenhancingautophagyinmice |