Effect of eNOS on Ischemic Postconditioning-Induced Autophagy against Ischemia/Reperfusion Injury in Mice
Autophagy is involved in the development of numerous illnesses, including ischemia/reperfusion (I/R). Endothelial nitric oxide synthase (eNOS) participates in the protective effects of ischemic postconditioning (IPostC). However, it remains unclear whether eNOS-mediated autophagy serves as a critica...
Main Authors: | , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Hindawi Limited
2019-01-01
|
Series: | BioMed Research International |
Online Access: | http://dx.doi.org/10.1155/2019/5201014 |
id |
doaj-f3f52853d08d4c47a4f37e9ff5ccd7e5 |
---|---|
record_format |
Article |
spelling |
doaj-f3f52853d08d4c47a4f37e9ff5ccd7e52020-11-25T01:06:36ZengHindawi LimitedBioMed Research International2314-61332314-61412019-01-01201910.1155/2019/52010145201014Effect of eNOS on Ischemic Postconditioning-Induced Autophagy against Ischemia/Reperfusion Injury in MiceJun Shao0Chen Miao1Zhi Geng2Maohong Gu3Yanhu Wu4Qingguo Li5Department of Cardiothoracic Surgery, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210011, ChinaDepartment of Pathology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, ChinaDepartment of Cardiothoracic Surgery, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210011, ChinaDepartment of Obstetrics and Gynecology, The Affiliated Nanjing First Hospital to Nanjing Medical University, Nanjing, Jiangsu 210006, ChinaDepartment of Cardiothoracic Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, ChinaDepartment of Cardiothoracic Surgery, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210011, ChinaAutophagy is involved in the development of numerous illnesses, including ischemia/reperfusion (I/R). Endothelial nitric oxide synthase (eNOS) participates in the protective effects of ischemic postconditioning (IPostC). However, it remains unclear whether eNOS-mediated autophagy serves as a critical role in IPostC in the hearts of mice, in protecting against I/R injury. In the present study, the hearts of mice with left anterior descending coronary artery ligation were studied as I/R models. H9c2 cells underwent exposure to hypoxia/reoxygenation (H/R) and were examined as in vitro model. IPostC reduced mice myocardial infarct size and improved the structure of the heart. IPostC increased the formation of autophagosomes and increased the phosphorylation of eNOS and adenosine monophosphate-activated protein kinase (AMPK). Autophagy and eNOS inhibition suppressed the cardioprotective effects of IPostC. AMPK or eNOS inhibition abolished the improvement effect of IPostC on autophagy. AMPK inhibition decreased eNOS phosphorylation in the heart. Additionally, H9c2 cells suffering hypoxia were used as in vitro model. Autophagy or eNOS inhibition abolished the protective effects of hypoxic postconditioning (HPostC) against H/R injury. AMPK and eNOS inhibition/knockout decreased autophagic activity in the HPostC group. These results indicated that IPostC protects the heart against I/R injury, partially via promoting AMPK/eNOS-mediated autophagy.http://dx.doi.org/10.1155/2019/5201014 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Jun Shao Chen Miao Zhi Geng Maohong Gu Yanhu Wu Qingguo Li |
spellingShingle |
Jun Shao Chen Miao Zhi Geng Maohong Gu Yanhu Wu Qingguo Li Effect of eNOS on Ischemic Postconditioning-Induced Autophagy against Ischemia/Reperfusion Injury in Mice BioMed Research International |
author_facet |
Jun Shao Chen Miao Zhi Geng Maohong Gu Yanhu Wu Qingguo Li |
author_sort |
Jun Shao |
title |
Effect of eNOS on Ischemic Postconditioning-Induced Autophagy against Ischemia/Reperfusion Injury in Mice |
title_short |
Effect of eNOS on Ischemic Postconditioning-Induced Autophagy against Ischemia/Reperfusion Injury in Mice |
title_full |
Effect of eNOS on Ischemic Postconditioning-Induced Autophagy against Ischemia/Reperfusion Injury in Mice |
title_fullStr |
Effect of eNOS on Ischemic Postconditioning-Induced Autophagy against Ischemia/Reperfusion Injury in Mice |
title_full_unstemmed |
Effect of eNOS on Ischemic Postconditioning-Induced Autophagy against Ischemia/Reperfusion Injury in Mice |
title_sort |
effect of enos on ischemic postconditioning-induced autophagy against ischemia/reperfusion injury in mice |
publisher |
Hindawi Limited |
series |
BioMed Research International |
issn |
2314-6133 2314-6141 |
publishDate |
2019-01-01 |
description |
Autophagy is involved in the development of numerous illnesses, including ischemia/reperfusion (I/R). Endothelial nitric oxide synthase (eNOS) participates in the protective effects of ischemic postconditioning (IPostC). However, it remains unclear whether eNOS-mediated autophagy serves as a critical role in IPostC in the hearts of mice, in protecting against I/R injury. In the present study, the hearts of mice with left anterior descending coronary artery ligation were studied as I/R models. H9c2 cells underwent exposure to hypoxia/reoxygenation (H/R) and were examined as in vitro model. IPostC reduced mice myocardial infarct size and improved the structure of the heart. IPostC increased the formation of autophagosomes and increased the phosphorylation of eNOS and adenosine monophosphate-activated protein kinase (AMPK). Autophagy and eNOS inhibition suppressed the cardioprotective effects of IPostC. AMPK or eNOS inhibition abolished the improvement effect of IPostC on autophagy. AMPK inhibition decreased eNOS phosphorylation in the heart. Additionally, H9c2 cells suffering hypoxia were used as in vitro model. Autophagy or eNOS inhibition abolished the protective effects of hypoxic postconditioning (HPostC) against H/R injury. AMPK and eNOS inhibition/knockout decreased autophagic activity in the HPostC group. These results indicated that IPostC protects the heart against I/R injury, partially via promoting AMPK/eNOS-mediated autophagy. |
url |
http://dx.doi.org/10.1155/2019/5201014 |
work_keys_str_mv |
AT junshao effectofenosonischemicpostconditioninginducedautophagyagainstischemiareperfusioninjuryinmice AT chenmiao effectofenosonischemicpostconditioninginducedautophagyagainstischemiareperfusioninjuryinmice AT zhigeng effectofenosonischemicpostconditioninginducedautophagyagainstischemiareperfusioninjuryinmice AT maohonggu effectofenosonischemicpostconditioninginducedautophagyagainstischemiareperfusioninjuryinmice AT yanhuwu effectofenosonischemicpostconditioninginducedautophagyagainstischemiareperfusioninjuryinmice AT qingguoli effectofenosonischemicpostconditioninginducedautophagyagainstischemiareperfusioninjuryinmice |
_version_ |
1725189272767561728 |