Dual role of cyclic GMP in cardiac cell survival.
Dual role of cyclic GMP in cardiac cell survival.
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环 GMP 在心脏细胞存活中的双重作用。
DOI：
10.1016/j.biocel.2013.04.027
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发表时间：
2013
期刊：
影响因子：
--
通讯作者：
Han,Jin
中科院分区：
文献类型：
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作者：
Xu,Zhelong;Lee,SungRyul;Han,Jin
环鸟苷酸通过激活蛋白激酶G（PKG）在心肌缺血再灌注损伤中发挥重要作用。我们发现cGMP通过蛋白激酶G（PKG）抑制糖原合成酶激酶3β（GSK-3β）的活性，从而抑制心肌细胞线粒体通透性转换孔（mPTP）的开放。虽然GSK-3β及其主要上游调节因子磷酸肌醇3-激酶（PI 3 K）/Akt对急性心脏保护至关重要，但PI 3 K/Akt的过度激活或GSK-3β失活也可导致心脏肥大。在这里，我们表明cGMP不仅通过PKG使GSK-3β失活（这导致急性心脏保护），而且还负调节心脏细胞中Akt活性（这可能导致预防肥大和心力衰竭，以及调节NO合成）。我们进一步发现cGMP对Akt活性的负调节作用不是通过PKG介导的，而是通过上调蛋白磷酸酶PP 2A活性。我们认为cGMP是一种多功能信号，在心脏细胞存活中具有双重有益作用。
It is well known that cyclic guanosine 3′,5′-monophosphate plays an important role in cardioprotection against ischemia/reperfusion injury through activation of protein kinase G (PKG). We found that cGMP prevents the mitochondrial permeability transition pore (mPTP) opening by inactivating glycogen synthase kinase 3β (GSK-3β) via protein kinase G (PKG) in cardiac H9c2 cells. While GSK-3β and its major upstream regulator phosphoinositide 3-kinase (PI3K)/Akt are critical for acute cardioprotection, an excessive activation of PI3K/Akt or GSK-3β inactivation can also lead to cardiac hypertrophy. Here, we show that cGMP not only inactivates GSK-3β through PKG (this leads to acute cardioprotection) but also negatively regulates Akt activity (this may lead to prevention of hypertrophy and heart failure, and the regulation of NO synthesis) in cardiac cells. We further found that the negative regulatory effect of cGMP on Akt activity is not mediated by PKG but may be through up-regulation of protein phosphatase PP2A activity. We propose that cGMP is a versatile signal with dual beneficial role in cardiac cell survival.