title: Role of Vitamin C in Cardioprotection of Ischemia/Reperfusion Injury by Activation of Mitochondrial KATP Channel.
abstract: How to provide effective prevention and treatment of myocardial ischemia/reperfusion (I/R) injury and study of the mechanism underlying I/R injury are hotspots of current research. This study aimed to elucidate the effect and cardioprotective mechanism of vitamin C (VC) on myocardial I/R injury. Our study introduced two different I/R models: I/R in vitro and oxygen-glucose deprivation/recovery (OGD/R) in primary neonatal rat cardiac myocytes. We used the mitochondrial permeability transition pore (mPTP) opener lonidamine (LND) and the mitochondrial KATP (mitoKATP) channel inhibitor 5-hydroxydecanoate (5-HD) to analyze the underlying mechanisms. We found that post-treatment with VC decreased I/R injury in our models. Post-treatment with VC significantly decreased I/R-induced injury, attenuated apoptosis, and maintained the functional integrity of mitochondria via alleviation of Ca(2+) overload, reactive oxygen species burst, inhibition of the opening of mPTP, and prevention of mitochondrial membrane potential (ΔΨm) depolarization. VC post-treatment increased the phosphorylation of Akt and glycogen synthase kinase (GSK)-3β. The present results demonstrate that VC might protect the myocardium from I/R-induced injury by inhibiting the mPTP opening via activation of mitoKATP channels. VC mediates cardioprotection via activation of the phosphatidyl inositol 3-kinase (PI3K)-Akt signaling pathway. These findings may contribute toward the development of novel strategies for clinical cardioprotection against I/R injury.
authors.affiliation: The Second Hospital of Hebei Medical University.
authors.forename: Jie
authors.initials: J
authors.lastname: Hao
authors.forename: Wei-Wei
authors.initials: WW
authors.lastname: Li
authors.forename: Hong
authors.initials: H
authors.lastname: Du
authors.forename: Zhi-Fang
authors.initials: ZF
authors.lastname: Zhao
authors.forename: Fan
authors.initials: F
authors.lastname: Liu
authors.forename: Jing-Chao
authors.initials: JC
authors.lastname: Lu
authors.forename: Xiu-Chun
authors.initials: XC
authors.lastname: Yang
authors.forename: Wei
authors.initials: W
authors.lastname: Cui
mesh_terms: D000818:Animals; D001205:Ascorbic Acid / Q000494:pharmacology*; D002316:Cardiotonic Agents / Q000494:pharmacology*; D003652:Decanoic Acids / Q000494:pharmacology; D006880:Hydroxy Acids / Q000494:pharmacology; D007191:Indazoles / Q000494:pharmacology; D008297:Male; D033681:Mitochondrial Membrane Transport Proteins / Q000378:metabolism*; D000083162:Mitochondrial Permeability Transition Pore; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D015221:Potassium Channels / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000378:metabolism
chemical_list: D002316:Cardiotonic Agents; D003652:Decanoic Acids; D006880:Hydroxy Acids; D007191:Indazoles; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D015221:Potassium Channels; C117780:mitochondrial K(ATP) channel; C052853:5-hydroxydecanoic acid; D001205:Ascorbic Acid; C016371:lonidamine