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首页> 外文期刊>Thrombosis and Haemostasis: Journal of the International Society on Thrombosis and Haemostasis >Differentiation of cGMP-dependent and -independent nitric oxide effects on platelet apoptosis and reactive oxygen species production using platelets lacking soluble guanylyl cyclase.
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Differentiation of cGMP-dependent and -independent nitric oxide effects on platelet apoptosis and reactive oxygen species production using platelets lacking soluble guanylyl cyclase.

机译：使用缺乏可溶性鸟苷酸环化酶的血小板，cGMP依赖性和非依赖性一氧化氮的差异对血小板凋亡和活性氧产生的影响。

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摘要

Platelet activation is an irreversible process resulting in platelet apoptosis and necrosis, and circulating platelets contain many components of the apoptotic machinery. Cyclic guanosine monophosphate (cGMP) generated by nitric oxide (NO) activated soluble guanylyl cyclase (sGC) plays a crucial role in preventing platelet activation. However, in addition to activation of sGC, cGMP-independent NO effects in platelets have been described. To differentiate between cGMP-dependent and -independent NO effects on platelet apoptosis and reactive oxygen species (ROS) production, we generated platelet-specific sGC-deficient mice (PS-GCKO). Platelet apoptosis was induced by a combination of thrombin/convulxin (Thr/Cvx) and assessed by phosphatidylserine (PS) surface exposure, and loss of the mitochondrial membrane potential. NO-induced inhibition of PS externalisation was mediated only by cGMP-dependent mechanisms. Inhibition of the mitochondrial membrane potential decrease at low NO concentration was also cGMP-dependent but became cGMP-independent at high NO concentrations. In contrast, inhibition of ROS formation at any NO concentration was mediated by cGMP-independent mechanisms, very likely due to direct radical scavenging. NO inhibits platelet apoptosis by cGMP-dependent mechanisms and ROS production by cGMP-independent mechanisms. The PS-GCKO mouse model is an important tool for the differentiation of cGMP-dependent and -independent NO effects on platelets.
机译：血小板活化是导致血小板凋亡和坏死的不可逆过程，循环中的血小板包含凋亡机制的许多成分。一氧化氮（NO）活化的可溶性鸟苷基环化酶（sGC）生成的环鸟苷单磷酸（cGMP）在防止血小板活化中起着至关重要的作用。然而，除了激活sGC，还描述了血小板中不依赖cGMP的NO作用。为了区分依赖cGMP的和不依赖NO的血小板凋亡和活性氧（ROS）产生，我们生成了血小板特异性sGC缺陷型小鼠（PS-GCKO）。凝血酶/惊厥毒素（Thr / Cvx）的组合可诱导血小板凋亡，并通过磷脂酰丝氨酸（PS）表面暴露和线粒体膜电位的丧失进行评估。 NO诱导的PS外部化抑制仅通过cGMP依赖性机制介导。在低NO浓度下抑制线粒体膜电位的降低也与cGMP依赖，但在高NO浓度下变得与cGMP无关。相反，在任何NO浓度下，对ROS形成的抑制作用均由cGMP独立机制介导，这很可能是由于直接自由基清除所致。 NO通过cGMP依赖性机制抑制血小板凋亡，并通过cGMP依赖性机制抑制ROS产生。 PS-GCKO小鼠模型是区分依赖cGMP和不依赖NO的血小板的重要工具。

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