Morphine Postconditioning Protects against Reperfusion Injury via Inhibiting JNK/p38 MAPK and Mitochondrial Permeability Transition Pores Signaling Pathways.
BACKGROUND
The purpose of this study was to determine whether c-jun NH2 amino-terminal kinases (JNK) and p38 mitogen-activated protein kinases (MAPK) were involved in morphine postconditioning (MpostC).


METHODS
The isolated rat hearts were randomly assigned into one of the following groups. Hearts in the time control (TC) group were constantly perfused for 105min. Hearts in the 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. Anisomycin (an activator of JNK/p38 kinases) was administered with or without morphine during the first 10 min of reperfusion following the 45 min of ischemia. Mitochondria and cytosolic proteins were prepared to detect mitochondrial permeability transition (MPT) and cytochrome C (Cyt-c) respectively.


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 anisomycin. I/R significantly increased the phosphorylation of JNK and p38 kinases, mitochondrial permeability transition (MPT) opening and Cyt-c release, while these effects were partly abolished by MpostC. The inhibitory effects of MpostC on the phosphorylation of JNK/p38 kinases, MPT opening and Cyt-c release were totally reversed by Anisocycin, which, used individually, did not show any influence on perfusion injury.


CONCLUSIONS
These findings suggest that MpostC protects isolated rat hearts against reperfusion injury via inhibiting JNK/p38 MAPKs and mitochondrial permeability transition pores signaling pathways.
Department of Anesthesiology, Affiliated Hospital of Qingdao University, Qingdao City, China.
Zuolei
Z
Chen
Xuewei
X
Zhang
Yingzhi
Y
Liu
Zhongkai
Z
Liu
D000701:Analgesics, Opioid / Q000494:pharmacology; D000818:Animals; D015153:Blotting, Western; D002316:Cardiotonic Agents / Q000494:pharmacology; D045304:Cytochromes c / Q000378:metabolism; D006321:Heart / Q000187:drug effects / Q000503:physiopathology; D066298:In Vitro Techniques; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D008297:Male; D008929:Mitochondria, Heart / Q000187:drug effects / Q000378:metabolism; D033681:Mitochondrial Membrane Transport Proteins / Q000378:metabolism*; D000083162:Mitochondrial Permeability Transition Pore; D009020:Morphine / Q000494:pharmacology*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D010766:Phosphorylation / Q000187:drug effects; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D015398:Signal Transduction / Q000187:drug effects*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
D000701:Analgesics, Opioid; D002316:Cardiotonic Agents; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D009020:Morphine; D045304:Cytochromes c; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases