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Morphine postconditioning protects against reperfusion injury: the role of protein kinase c-epsilon, extracellular signal-regulated kinase 1/2 and mitochondrial permeability transition pores


Chen, Zuolei; Spahn, Donat R; Zhang, Xuewei; Liu, Yingzhi; Chu, Haichen; Liu, Zhongkai (2016). Morphine postconditioning protects against reperfusion injury: the role of protein kinase c-epsilon, extracellular signal-regulated kinase 1/2 and mitochondrial permeability transition pores. Cellular Physiology and Biochemistry, 39(5):1930-1940.

Abstract

BACKGROUND/AIMS The purpose of this study was to investigate the implications of protein kinase C-epsilon (PKCε), Extracellular Signal-regulated Kinase 1/2 (ERK1/2) and mitochondrial permeability transition pore (mPTP) in myocardial protection induced by morphine postconditioning (MpostC). METHODS The isolated rat hearts were randomly assigned into one of eight groups. Hearts in time control (TC) group were constantly perfused for 105min. Hearts in ischemia-reperfusion (I/R) group were subjected to 45 min of ischemia followed by 1 h of reperfusion. MpostC was induced by 10 min of morphine administration at the onset of reperfusion. εV1-2 (an inhibitor of PKCε) and PD (an inhibitor of ERK1/2) was administered with or without morphine during the first 10 min of reperfusion following the 45 min of ischemia. I/R injury was assessed by functional parameters, creatine kinase-MB (CK-MB) release and infarct size (IS/AAR). Additional hearts were excised at 20 min following reperfusion to detect the membrane-specific translocation of PKCε, ERK1/2 phosphorylation, mitochondrial permeability transition (MPT) and cytochrome C (Cyt-c) release. RESULTS MpostC markedly reduced infarct size (IS/AAR), CK-MB release, and improved cardiac function recovery. However, these protective effects were partly abolished in the presence of εV1-2 or PD. Compared to TC group, the membrane translocation of PKCε, ERK1/2 phosphorylation, mPTP opening, and Cyt-c release were significantly increased in I/R hearts. MpostC further increased the membrane translocation of PKCε and ERK1/2 phosphorylation, and significantly inhibited mPTP opening and Cyt-c release. However, those protective effects induced by MpostC were abolished by εV1-2 or PD, which, used alone, showed no influence on reperfusion injury. CONCLUSIONS These findings suggest that MpostC protects isolated rat hearts against ischemia-reperfusion injury via activating PKCε-ERK1/2 pathway and inhibiting mPTP opening.

Abstract

BACKGROUND/AIMS The purpose of this study was to investigate the implications of protein kinase C-epsilon (PKCε), Extracellular Signal-regulated Kinase 1/2 (ERK1/2) and mitochondrial permeability transition pore (mPTP) in myocardial protection induced by morphine postconditioning (MpostC). METHODS The isolated rat hearts were randomly assigned into one of eight groups. Hearts in time control (TC) group were constantly perfused for 105min. Hearts in ischemia-reperfusion (I/R) group were subjected to 45 min of ischemia followed by 1 h of reperfusion. MpostC was induced by 10 min of morphine administration at the onset of reperfusion. εV1-2 (an inhibitor of PKCε) and PD (an inhibitor of ERK1/2) was administered with or without morphine during the first 10 min of reperfusion following the 45 min of ischemia. I/R injury was assessed by functional parameters, creatine kinase-MB (CK-MB) release and infarct size (IS/AAR). Additional hearts were excised at 20 min following reperfusion to detect the membrane-specific translocation of PKCε, ERK1/2 phosphorylation, mitochondrial permeability transition (MPT) and cytochrome C (Cyt-c) release. RESULTS MpostC markedly reduced infarct size (IS/AAR), CK-MB release, and improved cardiac function recovery. However, these protective effects were partly abolished in the presence of εV1-2 or PD. Compared to TC group, the membrane translocation of PKCε, ERK1/2 phosphorylation, mPTP opening, and Cyt-c release were significantly increased in I/R hearts. MpostC further increased the membrane translocation of PKCε and ERK1/2 phosphorylation, and significantly inhibited mPTP opening and Cyt-c release. However, those protective effects induced by MpostC were abolished by εV1-2 or PD, which, used alone, showed no influence on reperfusion injury. CONCLUSIONS These findings suggest that MpostC protects isolated rat hearts against ischemia-reperfusion injury via activating PKCε-ERK1/2 pathway and inhibiting mPTP opening.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Institute of Anesthesiology
Dewey Decimal Classification:610 Medicine & health
Language:German
Date:2016
Deposited On:21 Nov 2016 10:37
Last Modified:08 Dec 2017 20:55
Publisher:Karger
ISSN:1015-8987
Additional Information:The final, published version of this article is available at http://www.karger.com/?doi=10.1159/000447890
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1159/000447890
PubMed ID:27771708

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