Mechanism for resveratrol-induced cardioprotection against reperfusion injury involves glycogen synthase kinase 3beta and mitochondrial permeability transition pore.
Mechanism for resveratrol-induced cardioprotection against reperfusion injury involves glycogen synthase kinase 3beta and mitochondrial permeability transition pore.
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DOI：
10.1016/j.ejphar.2008.12.024
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发表时间：
2009-02-14
影响因子：
5
通讯作者：
Xu Z
中科院分区：
文献类型：
--
作者：
Xi J;Wang H;Mueller RA;Norfleet EA;Xu Z
白藜芦醇预处理可通过诱导药理预处理来保护心脏。白藜芦醇在再灌注时是否对心脏有保护作用尚不清楚。我们检查了白藜芦醇在再灌注时对心肌梗死面积的影响，并研究了这种影响的机制。取离体大鼠心脏缺血30 min，再灌注2 h，取危险区心肌样本进行Western blot分析。用分光光度法测定线粒体肿胀，在520 nm处吸光度降低（A520）。白藜芦醇减少梗死面积，防止心肌线粒体肿胀。白藜芦醇可通过环鸟苷单磷酸(cGMP)/蛋白激酶G （PKG）通路增强GSK-3β在再灌注时的磷酸化。白藜芦醇通过cGMP/PKG途径将GSK-3β从细胞质转运到线粒体。进一步的研究表明，线粒体GSK-3β与亲环蛋白D共免疫沉淀，但不与VDAC（电压依赖性阴离子通道）或ANT（腺嘌呤核苷酸转运体）共免疫沉淀。这些数据表明，白藜芦醇可能通过将GSK-3β从细胞质转运到线粒体来靶向mPTP，从而防止心肌再灌注损伤。易位的GSK-3β可能最终与亲环蛋白D相互作用以调节mPTP的开放。
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.
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DOI：
10.1152/ajpheart.00453.2004
发表时间：
2005-01-01
影响因子：
4.8
作者：
Das, S;Cordis, GA;Das, DK
通讯作者：
Das, DK
影响因子：
64.8
作者：
Baines, CP;Kaiser, RA;Molkentin, JD
通讯作者：
Molkentin, JD
影响因子：
5
作者：
Argaud, Laurent;Gateau-Roesch, Odile;Ovize, Michel
通讯作者：
Ovize, Michel
影响因子：
1.7
作者：
Bijur, GN;Jope, RS
通讯作者：
Jope, RS
影响因子：
5
作者：
Bradamante, S;Barenghi, L;De Jong, JW
通讯作者：
De Jong, JW