title: Mitochondrial permeability transition pore plays a role in the cardioprotection of CB2 receptor against ischemia-reperfusion injury.
abstract: The aim of this study was to investigate whether the mitochondrial permeability transition pore (MPTP) opening was involved in the protective effects of CB2 receptor against ischemia-reperfusion (I-R) injury. For this, isolated perfused rat hearts were subjected to 30 min global ischemia followed by 120 min reperfusion, and left ventricle function was recorded. At the end of reperfusion, the infarct size in the hearts was measured by staining with triphenyltetrazolium chloride. MPTP opening and the mitochondrial membrane potential (ΔΨ(m)) were measured by flow cytometry. Western blot analysis of cytochrome c in the mitochondrion and cytosol, as well as ERK1/2 and p-ERK1/2 were performed. Administration of CB2 receptor agonist JWH133 before ischemia significantly improved the recovery of cardiac ventricular function during reperfusion, increased coronary flow, reduced infarct size, prevented the loss of ΔΨ(m) and MPTP opening, reduced the release of cytochrome c from mitochondria, and increased levels of p-ERK1/2. These effects of JWH133 were abolished by pretreatment with CB2 receptor antagonist AM630, or ERK1/2 inhibitor PD98059. Furthermore, JWH133 reversed the MPTP opening induced by atractyloside. The protective effect of JWH133 on the heart against I-R injury may be through increased ERK1/2 phosphorylation, inhibiting MPTP opening.
authors.affiliation: a Department of Physiology, Hebei Medical University, Shijiazhuang 050017, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Li
authors.forename: Hui-cai
authors.initials: HC
authors.lastname: Guo
authors.forename: Leonid N
authors.initials: LN
authors.lastname: Maslov
authors.forename: Xiao-wen
authors.initials: XW
authors.lastname: Qiao
authors.forename: Jing-jing
authors.initials: JJ
authors.lastname: Zhou
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000818:Animals; D002186:Cannabinoids / Q000494:pharmacology; D045304:Cytochromes c / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000502:physiology; D008297:Male; D008929:Mitochondria, Heart / Q000187:drug effects / Q000378:metabolism; D033681:Mitochondrial Membrane Transport Proteins / Q000187:drug effects / Q000502:physiology*; D000083162:Mitochondrial Permeability Transition Pore; D009203:Myocardial Infarction / Q000473:pathology / Q000517:prevention & control; D015428:Myocardial Reperfusion Injury / Q000378:metabolism* / Q000503:physiopathology / Q000517:prevention & control; D051381:Rats; D017207:Rats, Sprague-Dawley; D043885:Receptor, Cannabinoid, CB2 / Q000819:agonists / Q000378:metabolism*
chemical_list: D002186:Cannabinoids; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D043885:Receptor, Cannabinoid, CB2; D045304:Cytochromes c; C432747:1,1-dimethylbutyl-1-deoxy-Delta(9)-THC