Role of Vitamin C in Cardioprotection of Ischemia/Reperfusion Injury by Activation of Mitochondrial KATP Channel
| Autor: | Zhi-Fang Zhao, Hong Du, Fan Liu, Wei-Wei Li, Jingchao Lu, Jie Hao, Wei Cui, Xiuchun Yang |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Cardioprotection Chemistry MPTP General Chemistry General Medicine Mitochondrion Pharmacology medicine.disease 03 medical and health sciences chemistry.chemical_compound 030104 developmental biology Mitochondrial permeability transition pore GSK-3 Drug Discovery medicine Protein kinase B Reperfusion injury PI3K/AKT/mTOR pathway |
| Zdroj: | CHEMICAL & PHARMACEUTICAL BULLETIN. 64:548-557 |
| ISSN: | 1347-5223 0009-2363 |
| DOI: | 10.1248/cpb.c15-00693 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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