Sodium Ferulate attenuates anoxia/reoxygenation-induced calcium overload in neonatal rat cardiomyocytes by NO/cGMP/PKG pathway
Sodium Ferulate attenuates anoxia/reoxygenation-induced calcium overload in neonatal rat cardiomyocytes by NO/cGMP/PKG pathway
复制标题
阿魏酸钠通过 NO/cGMP/PKG 途径减轻新生大鼠心肌细胞缺氧/复氧引起的钙超载
DOI：
10.1016/j.ejphar.2008.12.003
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发表时间：
2009-01-28
影响因子：
5
通讯作者：
He, Ming
中科院分区：
文献类型：
--
作者：
Chen, He-Ping;Liao, Zhang-Ping;He, Ming
细胞内钙超载的发生是心肌缺血/再灌注或缺氧/复氧损伤的重要病理生理因素。最近的研究表明，阿魏酸钠（SF）可刺激一氧化氮（NO）的产生，并对缺血再灌注的心脏发挥心脏保护作用。然而，尚未确定 SF 的心脏保护作用是否与通过 NO/环鸟苷酸 (cGMP)/环鸟苷酸 (cGMP) 依赖性蛋白激酶 (PKG) 途径抑制 Ca2+ 过载有关。在这项工作中，心肌细胞与100、200、400或800μM SF孵育3小时后，诱导缺氧/复氧损伤，并适当测量细胞内Ca2+浓度、NO合酶（NOS）活性、鸟苷酸环化酶活性、NO和cGMP形成。结果表明，SF 处理浓度依赖性地抑制缺氧/复氧引起的钙超载。我们还证明，SF（100-800 μM）浓度通过增加心肌细胞中的 NOS 活性和鸟苷酸环化酶活性，依赖性地增强 NO 和 cGMP 形成。相反，通过添加NOS抑制剂、NO清除剂、可溶性鸟苷酸环化酶抑制剂和PKG抑制剂：N-G-硝基-L-精氨酸甲酯(L-NAME，100μM)、2-(4-羧基苯基)-4,4,5,5-四甲基咪唑-1-氧基-3-氧化物，SF对钙超载的抑制显着减弱。 (c-PTIO，1.0μM)、1H-[1,2,4]恶二唑并[4,3-α]喹喔啉-1-酮(ODQ，20μM)和KT5823(0.2μM)。我们的研究结果表明，SF 通过 NO/cGMP/PKG 信号通路显着减弱缺氧/复氧诱导的 Ca2+ 过载，并提高培养心肌细胞的细胞存活率。 (C) 2008 Elsevier B.V. 保留所有权利。
Development of intracellular calcium overload is an important pathophysiological factor in myocardial ischemia/reperfusion or anoxia/reoxygenation injury. Recent studies have shown that Sodium Ferulate (SF) stimulates nitric oxide (NO) production and exerts a cardioprotective effect in the ischemia-reperfused heart. However, it has not been determined whether the cardioprotection of SF is associated with suppression of Ca2+ overload via NO/cyclic GMP (cGMP)/cGMP-dependent protein kinase (PKG) pathway. In this work, after cardiomyocytes were incubated with 100, 200, 400, or 800 mu M SF for 3 h, anoxia/reoxygenation injury was induced and intracellular Ca2+ concentration, NO synthase (NOS) activity, guanylate cyclase activity, NO, and cGMP formation were measured appropriately. The results showed that treatment with SF concentration-dependently inhibited calcium overload induced by anoxia/reoxygenation. We also demonstrated that SF (100-800 mu M) concentration dependently enhanced NO and cGMP formation through increasing NOS activity and guanylate cyclase activity in the cardiomyocytes. On the contrary, inhibition of calcium overload by SF was markedly attenuated by addition of an NOS inhibitor, an NO scavenger, an soluble guanylate cyclase inhibitor, and a PKG inhibitor: N-G-nitro-L-arginine methyl ester (L-NAME, 100 mu M), 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazole-1-oxyl-3-oxide (c-PTIO, 1.0 mu M), 1H-[1, 2, 4] oxadiazolo [4, 3-alpha] quinoxalin-1-one (ODQ, 20 mu M) and KT5823 (0.2 mu M), respectively. Our findings indicate that SF significantly attenuates anoxia/reoxygenation-induced Ca2+ overload and improves cell survival in cultured cardiomyocytes through NO/cGMP/PKG signal pathway. (C) 2008 Elsevier B.V. All rights reserved.