Astragaloside IV inhibits oxidative stress-induced mitochondrial permeability transition pore opening by inactivating GSK-3β via nitric oxide in H9c2 cardiac cells.
Astragaloside IV inhibits oxidative stress-induced mitochondrial permeability transition pore opening by inactivating GSK-3β via nitric oxide in H9c2 cardiac cells.
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DOI：
10.1155/2012/935738
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发表时间：
2012
影响因子：
--
通讯作者：
Xu Z
中科院分区：
文献类型：
--
作者：
He Y;Xi J;Zheng H;Zhang Y;Jin Y;Xu Z
Objective.本研究旨在探讨黄芪甲苷IV是否通过糖原合成酶激酶3β（GSK-3β）调节H9 c2细胞线粒体通透性转换孔（mPTP）开放。方法.将H9 c2细胞暴露于黄芪甲苷IV 20分钟。用Western blot法测定GSK-3β（Ser 9）、Akt（Ser 473）和VASP（Ser 239）的活性。通过测量线粒体膜电位（Δ μ m）来评估mPTP开放。用4-氨基-5-甲氨基-2 ′，7′-二氟荧光素（DAF-FM）二乙酸酯测定一氧化氮（NO）的生成。用共聚焦显微镜获得荧光图像。结果黄芪甲苷能显著增强GSK-3β的磷酸化水平，并能阻止H2 O2诱导的Δ β m的丢失。这些作用的黄芪甲苷逆转磷脂酰肌醇3-激酶（PI 3 K）抑制剂LY 294002，NO敏感的鸟苷酸环化酶选择性抑制剂ODQ，和PKG抑制剂KT 5823。黄芪甲苷激活Akt和PKG。黄芪甲苷IV也显示出增加NO的产生，L-NAME和LY 294002逆转了这种作用。再灌注时应用黄芪甲苷可减少模拟缺血/再灌注引起的细胞死亡，表明黄芪甲苷可预防再灌注损伤。结论.提示黄芪甲苷通过NO/cGMP/PKG信号通路抑制GSK-3β的活性，从而抑制mPTP开放和再灌注损伤。NOS负责NO的产生，并通过PI 3 K/Akt途径激活。
Objective. This study aimed to investigate whether astragaloside IV modulates the mitochondrial permeability transition pore (mPTP) opening through glycogen synthase kinase 3β (GSK-3β) in H9c2 cells. Methods. H9c2 cells were exposed to astragaloside IV for 20 min. GSK-3β (Ser9), Akt (Ser473), and VASP (Ser239) activities were determined with western blot. The mPTP opening was evaluated by measuring mitochondrial membrane potential (ΔΨm). Nitric oxide (NO) generation was measured by 4-amino-5-methylamino-2′, 7′-difluorofluorescein (DAF-FM) diacetate. Fluorescence images were obtained with confocal microscopy. Results. Astragaloside IV significantly enhanced GSK-3β phosphorylation and prevented H2O2-induced loss of ΔΨm. These effects of astragaloside IV were reversed by the phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002, the NO sensitive guanylyl cyclase selective inhibitor ODQ, and the PKG inhibitor KT5823. Astragaloside IV activated Akt and PKG. Astragaloside IV was also shown to increase NO production, an effect that was reversed by L-NAME and LY294002. Astragaloside IV applied at reperfusion reduced cell death caused by simulated ischemia/reperfusion, indicating that astragaloside IV can prevent reperfusion injury. Conclusions. These data suggest that astragaloside IV prevents the mPTP opening and reperfusion injury by inactivating GSK-3β through the NO/cGMP/PKG signaling pathway. NOS is responsible for NO generation and is activated by the PI3K/Akt pathway.
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DOI：
10.1111/j.1440-1681.2008.05059.x
发表时间：
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