title: Involvement of Bcl-2 Signal Pathway in the Protective Effects of Apigenin on Anoxia/Reoxygenation-induced Myocardium Injury.
abstract: Apigenin is a type of flavonoids, which has been demonstrated to protect myocardium against ischemia/reperfusion (I/R) injury. However, the mechanism is still unclear. We hypothesized that the mechanism of cardioprotective action of apigenin on the I/R-induced injury might be caused via B-cell lymphoma (Bcl) signaling pathway. In this study, an in vitro I/R model was replicated on Langendorff-perfused heart and H9c2 cardiomyocytes by anoxia/reoxygenation (A/R) treatment. The recovery of cardiac contractile function, infarct size, lactate dehydrogenase (LDH) and creatine kinase (CK) in the perfusate, the expression and activity of Bcl-2 and caspase-3, and cardiomyocyte apoptosis were measured in the Langendorff heart undergoing A/R injury. In addition, the cell viability, LDH release, intracellular reactive oxygen species (ROS), mitochondrial membrane potential (Δψm), expression of cytochrome c in the cytosol, and cell apoptosis were examined in the culture of H9c2 cardiomyocytes after the A/R. The results showed that apigenin significantly improved rat heart contractile function, reduced LDH release, infarct size and apoptotic rate, upregulated the expression of Bcl-2 and caspase-3, and downregulated the expression of cleaved caspase-3 after the A/R. Moreover, apigenin increased the cell viability and decreased the release of LDH, production of reactive oxygen species, release of mitochondrial cytochrome c into the cytosol, and cell apoptosis in the culture of H9c2 cardiomyocytes after the A/R. In addition, inhibition of Bcl-2 activity by ABT-737 markedly attenuated the protective effect of apigenin on the A/R-induced myocardium injury. Taken together, we firstly demonstrated that the effect of apigenin against A/R injury in cardiomyocytes involves Bcl-2 signal pathway and at least partly depends on its effect of upregulating the expression of Bcl-2.
authors.affiliation: *Jiangxi Provincial Key Laboratory of Basic Pharmacology, Nanchang University School of Pharmaceutical Science, Nanchang, China; and †Jiangxi Provincial Key Laboratory of Molecular Medicine at the Second Affiliated Hospital, Nanchang University, Nanchang, China.
authors.forename: Chuanjun
authors.initials: C
authors.lastname: Chen
authors.forename: Huan
authors.initials: H
authors.lastname: He
authors.forename: Yong
authors.initials: Y
authors.lastname: Luo
authors.forename: Min
authors.initials: M
authors.lastname: Zhou
authors.forename: Dong
authors.initials: D
authors.lastname: Yin
authors.forename: Ming
authors.initials: M
authors.lastname: He
mesh_terms: D000818:Animals; D047310:Apigenin / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D002316:Cardiotonic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002460:Cell Line; D000860:Hypoxia / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D009203:Myocardial Infarction / Q000378:metabolism / Q000517:prevention & control*; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects* / Q000502:physiology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000819:agonists / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
chemical_list: D002316:Cardiotonic Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D047310:Apigenin