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.
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.
Authors: Yan-Ping Huang; Tian-Hua Yang; Zhi-Yan Jin; Ya Wang; Hong-Wei Ye; Qin Gao; Zheng-Hong Li Journal: Nan Fang Yi Ke Da Xue Xue Bao Date: 2018-05-20
Authors: Carolin Torregroza; Chiara O Glashoerster; Katharina Feige; Martin Stroethoff; Annika Raupach; André Heinen; Markus W Hollmann; Ragnar Huhn Journal: Int J Mol Sci Date: 2021-11-19 Impact factor: 5.923
Authors: Ingo Eitel; Juan Wang; Thomas Stiermaier; Georg Fuernau; Hans-Josef Feistritzer; Alexander Joost; Alexander Jobs; Moritz Meusel; Christian Blodau; Steffen Desch; Suzanne de Waha-Thiele; Harald Langer; Holger Thiele Journal: J Clin Med Date: 2020-03-09 Impact factor: 4.241