Propofol Inhibits Ischemia/Reperfusion-Induced Cardiotoxicity Through the Protein Kinase C/Nuclear Factor Erythroid 2-Related Factor Pathway
Both hydrogen peroxide (H2O2, H) and ischemia/reperfusion (I/R) can damage cardiomyocytes, which was inhibited by propofol (P). The present research was designed to examine whether propofol can reduce myocardial I/R injury by activating protein kinase C (PKC)/nuclear factor erythroid-2-related facto...
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2021-05-01
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doaj-c8844a1254dc46948947ffed35dbff622021-05-13T09:24:46ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122021-05-011210.3389/fphar.2021.655726655726Propofol Inhibits Ischemia/Reperfusion-Induced Cardiotoxicity Through the Protein Kinase C/Nuclear Factor Erythroid 2-Related Factor PathwayShengqiang Li0Zhen Lei1Meng Zhao2Yonghao Hou3Di Wang4Xingli Xu5Xiaowen Lin6Jingxin Li7Shuhai Tang8Jingui Yu9Tao Meng10Department of Anesthesiology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, ChinaDepartment of Anesthesiology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, ChinaDepartment of Anesthesiology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, ChinaDepartment of Anesthesiology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, ChinaDepartment of Anesthesiology, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, ChinaDepartment of Cardiovascular Ultrasound and Non-invasive Cardiology, Sichuan People’s Hospital, Chengdu, ChinaDepartment of Pain Management, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, ChinaDepartment of Physiology, Cheeloo College of Medicine, Shandong University, Jinan, ChinaDepartment of Anesthesiology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, ChinaDepartment of Anesthesiology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, ChinaDepartment of Anesthesiology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, ChinaBoth hydrogen peroxide (H2O2, H) and ischemia/reperfusion (I/R) can damage cardiomyocytes, which was inhibited by propofol (P). The present research was designed to examine whether propofol can reduce myocardial I/R injury by activating protein kinase C (PKC)/nuclear factor erythroid-2-related factor 2 (NRF2) pathway in H9C2 cells and rat Langendorff models. H9C2 cells were disposed of no reagents (C), H2O2 for 24 h (H), propofol for 1 h before H2O2 (H+P), and chelerythrine (CHE, PKC inhibitor) for 1 h before propofol and H2O2 (H+P+CHE). N = 3. The PKC gene of H9C2 was knocked down by siRNA and overexpressed by phorbol 12-myristate 13-acetate (PMA, PKC agonist). The cell viability and the expressions of PKC, NRF2, or heme oxygenase-1(HO-1) were evaluated. Propofol significantly reduced H9C2 cell mortality induced by H2O2, and significantly increased NRF2 nuclear location and HO-1 expression, which were restrained by siRNA knockout of PKC and promoted by PMA. Rat hearts were treated with KrebsHenseleit solution for 120 min (C), with (I/R+P) or without (I/R) propofol for 20 min before stopping perfusion for 30 min and reperfusion for 60 min, and CHE for 10 min before treated with propofol. N = 6. The levels of lactate dehydrogenase (LDH), superoxide dismutase (SOD), and creatine kinase-MB (CK-MB) in perfusion fluid and antioxidant enzymes in the myocardium were assessed. I/R, which increased LDH and CK-MB expression and reduced SOD expression, boosted the pathological damage and infarcts of the myocardium after reperfusion. However, propofol restrained all these effects, an activity that was antagonized by CHE. The results suggest that propofol pretreatment protects against I/R injury by activating of PKC/NRF2 pathway.https://www.frontiersin.org/articles/10.3389/fphar.2021.655726/fullpropofolheartischemia reperfusionprotein kinase Cnuclear factor erythroid-2- related factorheme oxygenase-1 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Shengqiang Li Zhen Lei Meng Zhao Yonghao Hou Di Wang Xingli Xu Xiaowen Lin Jingxin Li Shuhai Tang Jingui Yu Tao Meng |
spellingShingle |
Shengqiang Li Zhen Lei Meng Zhao Yonghao Hou Di Wang Xingli Xu Xiaowen Lin Jingxin Li Shuhai Tang Jingui Yu Tao Meng Propofol Inhibits Ischemia/Reperfusion-Induced Cardiotoxicity Through the Protein Kinase C/Nuclear Factor Erythroid 2-Related Factor Pathway Frontiers in Pharmacology propofol heart ischemia reperfusion protein kinase C nuclear factor erythroid-2- related factor heme oxygenase-1 |
author_facet |
Shengqiang Li Zhen Lei Meng Zhao Yonghao Hou Di Wang Xingli Xu Xiaowen Lin Jingxin Li Shuhai Tang Jingui Yu Tao Meng |
author_sort |
Shengqiang Li |
title |
Propofol Inhibits Ischemia/Reperfusion-Induced Cardiotoxicity Through the Protein Kinase C/Nuclear Factor Erythroid 2-Related Factor Pathway |
title_short |
Propofol Inhibits Ischemia/Reperfusion-Induced Cardiotoxicity Through the Protein Kinase C/Nuclear Factor Erythroid 2-Related Factor Pathway |
title_full |
Propofol Inhibits Ischemia/Reperfusion-Induced Cardiotoxicity Through the Protein Kinase C/Nuclear Factor Erythroid 2-Related Factor Pathway |
title_fullStr |
Propofol Inhibits Ischemia/Reperfusion-Induced Cardiotoxicity Through the Protein Kinase C/Nuclear Factor Erythroid 2-Related Factor Pathway |
title_full_unstemmed |
Propofol Inhibits Ischemia/Reperfusion-Induced Cardiotoxicity Through the Protein Kinase C/Nuclear Factor Erythroid 2-Related Factor Pathway |
title_sort |
propofol inhibits ischemia/reperfusion-induced cardiotoxicity through the protein kinase c/nuclear factor erythroid 2-related factor pathway |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Pharmacology |
issn |
1663-9812 |
publishDate |
2021-05-01 |
description |
Both hydrogen peroxide (H2O2, H) and ischemia/reperfusion (I/R) can damage cardiomyocytes, which was inhibited by propofol (P). The present research was designed to examine whether propofol can reduce myocardial I/R injury by activating protein kinase C (PKC)/nuclear factor erythroid-2-related factor 2 (NRF2) pathway in H9C2 cells and rat Langendorff models. H9C2 cells were disposed of no reagents (C), H2O2 for 24 h (H), propofol for 1 h before H2O2 (H+P), and chelerythrine (CHE, PKC inhibitor) for 1 h before propofol and H2O2 (H+P+CHE). N = 3. The PKC gene of H9C2 was knocked down by siRNA and overexpressed by phorbol 12-myristate 13-acetate (PMA, PKC agonist). The cell viability and the expressions of PKC, NRF2, or heme oxygenase-1(HO-1) were evaluated. Propofol significantly reduced H9C2 cell mortality induced by H2O2, and significantly increased NRF2 nuclear location and HO-1 expression, which were restrained by siRNA knockout of PKC and promoted by PMA. Rat hearts were treated with KrebsHenseleit solution for 120 min (C), with (I/R+P) or without (I/R) propofol for 20 min before stopping perfusion for 30 min and reperfusion for 60 min, and CHE for 10 min before treated with propofol. N = 6. The levels of lactate dehydrogenase (LDH), superoxide dismutase (SOD), and creatine kinase-MB (CK-MB) in perfusion fluid and antioxidant enzymes in the myocardium were assessed. I/R, which increased LDH and CK-MB expression and reduced SOD expression, boosted the pathological damage and infarcts of the myocardium after reperfusion. However, propofol restrained all these effects, an activity that was antagonized by CHE. The results suggest that propofol pretreatment protects against I/R injury by activating of PKC/NRF2 pathway. |
topic |
propofol heart ischemia reperfusion protein kinase C nuclear factor erythroid-2- related factor heme oxygenase-1 |
url |
https://www.frontiersin.org/articles/10.3389/fphar.2021.655726/full |
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