cGMP-dependent protein kinase contributes to hydrogen sulfide-stimulated vasorelaxation.
cGMP-dependent protein kinase contributes to hydrogen sulfide-stimulated vasorelaxation.
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DOI：
10.1371/journal.pone.0053319
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Cirino G
中科院分区：
文献类型：
--
作者：
Bucci M;Papapetropoulos A;Vellecco V;Zhou Z;Zaid A;Giannogonas P;Cantalupo A;Dhayade S;Karalis KP;Wang R;Feil R;Cirino G
越来越多的证据表明，硫化氢（H2S）是哺乳动物细胞中的信号分子。在心血管系统中，H2S增强血管舒张和血管生成。H2S诱导的血管舒张被假设为通过ATP敏感性钾通道（KATP）发生;然而，我们最近证明，它也增加了组织中的cGMP水平。在此，我们研究了cGMP依赖性蛋白激酶-I参与硫化氢诱导的血管舒张。在有或无内皮的苯肾上腺素收缩的主动脉环上研究了H2S对血管张力的影响。通过酶免疫测定法测定培养的细胞或分离的血管中的cGMP水平。用西地那非预处理主动脉环减弱了NaHS诱导的舒张，证实了先前的研究结果，即H2S是磷酸二酯酶抑制剂。此外，胱硫醚γ裂解酶基因敲除小鼠的血管组织cGMP水平低于野生型对照小鼠。用NaHS（一种快速释放H2S的供体）处理主动脉环，以时间依赖性方式增强血管扩张剂刺激的磷蛋白的磷酸化，表明cGMP依赖性蛋白激酶（PKG）在暴露于H2S后被激活。用PKG-I抑制剂（DT-2）孵育主动脉环可减弱NaHS刺激的舒张。有趣的是，对缓慢释放H2S供体（GYY 4137）的血管舒张反应不受DT-2的影响，表明该供体通过PKG非依赖性途径扩张小鼠主动脉。在PKG-I敲除小鼠（PKG-I−/−）的血管中，对NaHS和L-半胱氨酸（H2S产生的底物）的扩张反应降低。此外，格列本脲可抑制野生型动物血管中NaHS诱导的血管舒张，但不能抑制PKG-I−/−，这表明KATP和PKG之间存在相互作用。我们的研究结果证实了cGMP在血管对NaHS的反应中的作用，并表明PKG-I的基因缺失减弱了NaHS和L-半胱氨酸刺激的血管舒张。
A growing body of evidence suggests that hydrogen sulfide (H2S) is a signaling molecule in mammalian cells. In the cardiovascular system, H2S enhances vasodilation and angiogenesis. H2S-induced vasodilation is hypothesized to occur through ATP-sensitive potassium channels (KATP); however, we recently demonstrated that it also increases cGMP levels in tissues. Herein, we studied the involvement of cGMP-dependent protein kinase-I in H2S-induced vasorelaxation. The effect of H2S on vessel tone was studied in phenylephrine-contracted aortic rings with or without endothelium. cGMP levels were determined in cultured cells or isolated vessel by enzyme immunoassay. Pretreatment of aortic rings with sildenafil attenuated NaHS-induced relaxation, confirming previous findings that H2S is a phosphodiesterase inhibitor. In addition, vascular tissue levels of cGMP in cystathionine gamma lyase knockouts were lower than those in wild-type control mice. Treatment of aortic rings with NaHS, a fast releasing H2S donor, enhanced phosphorylation of vasodilator-stimulated phosphoprotein in a time-dependent manner, suggesting that cGMP-dependent protein kinase (PKG) is activated after exposure to H2S. Incubation of aortic rings with a PKG-I inhibitor (DT-2) attenuated NaHS-stimulated relaxation. Interestingly, vasodilatory responses to a slowly releasing H2S donor (GYY 4137) were unaffected by DT-2, suggesting that this donor dilates mouse aorta through PKG-independent pathways. Dilatory responses to NaHS and L-cysteine (a substrate for H2S production) were reduced in vessels of PKG-I knockout mice (PKG-I−/−). Moreover, glibenclamide inhibited NaHS-induced vasorelaxation in vessels from wild-type animals, but not PKG-I−/−, suggesting that there is a cross-talk between KATP and PKG. Our results confirm the role of cGMP in the vascular responses to NaHS and demonstrate that genetic deletion of PKG-I attenuates NaHS and L-cysteine-stimulated vasodilation.
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影响因子：
7.3
作者：
Mustafa AK;Gadalla MM;Snyder SH
通讯作者：
Snyder SH
影响因子：
3.7
作者：
Chai Y;Zhang DM;Lin YF
通讯作者：
Lin YF
DOI：
10.1073/pnas.97.26.14772
发表时间：
2000-12-19
影响因子：
11.1
作者：
Dostmann, WRG;Taylor, MS;Tegge, WJ
通讯作者：
Tegge, WJ
影响因子：
20.1
作者：
Mustafa AK;Sikka G;Gazi SK;Steppan J;Jung SM;Bhunia AK;Barodka VM;Gazi FK;Barrow RK;Wang R;Amzel LM;Berkowitz DE;Snyder SH
通讯作者：
Snyder SH
影响因子：
3.6
作者：
Ibarra-Alvarado, C;Galle, J;Schmidt, HHHW
通讯作者：
Schmidt, HHHW