Mechanism for resveratrol-induced cardioprotection against reperfusion injury involves glycogen synthase kinase 3β and mitochondrial permeability transition pore

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• 作者：Jinkun Xi ; Huihua Wang ; Robert A. Mueller ; Edward A. Norfleet ; Zhelong Xu
• 关键词：Resveratrol ; Reperfusion injury ; Glycogen synthase kinase 3β ; Mitochondrial permeability transition pore
• 刊名：European Journal of Pharmacology
• 出版年：2009
• 出版时间：14 February 2009
• 年：2009
• 卷：604
• 期：1-3
• 页码：111-116
• 全文大小：411 K

文摘

Resveratrol pretreatment can protect the heart by inducing pharmacological preconditioning. Whether resveratrol protects the heart when applied at reperfusion remains unknown. We examined the effect of resveratrol on myocardial infarct size when given at reperfusion and investigated the mechanism underlying the effect. Isolated rat hearts were subjected to 30 min ischemia followed by 2 h of reperfusion, and myocardial samples were collected from the risk zone for Western blot analysis. Mitochondrial swelling was spectrophotometrically measured as a decrease in absorbance at 520 nm (A₅₂₀). Resveratrol reduced infarct size and prevented cardiac mitochondrial swelling. Resveratrol enhanced GSK-3β phosphorylation upon reperfusion, an effect that was mediated by the cyclic guanosine monophosphate (cGMP)/protein kinase G (PKG) pathway. Resveratrol translocated GSK-3β from cytosol to mitochondria via the cGMP/PKG pathway. Further studies showed that mitochondrial GSK-3β was co-immunoprecipitated with cyclophilin D but not with VDAC (voltage dependent anion channel) or ANT (adenine nucleotide translocator). These data suggest that resveratrol prevents myocardial reperfusion injury presumably by targeting the mPTP through translocation of GSK-3β from cytosol to mitochondria. Translocated GSK-3β may ultimately interact with cyclophilin D to modulate the mPTP opening.