The vasodilatory effect of sulfur dioxide via SGC/cGMP/PKG pathway in association with sulfhydryl-dependent dimerization.
The vasodilatory effect of sulfur dioxide via SGC/cGMP/PKG pathway in association with sulfhydryl-dependent dimerization.
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二氧化硫通过 SGC/cGMP/PKG 途径的血管舒张作用与巯基依赖性二聚化相关。
DOI：
10.1152/ajpregu.00101.2015
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发表时间：
2016-06
期刊：
影响因子：
--
通讯作者：
Jin HF
中科院分区：
文献类型：
--
作者：
Du SX;Huang P;Tang CS;Du JB;Jin HF
本研究旨在探讨可溶性鸟苷酸环化酶（sGC）/环磷酸鸟苷（cGMP）/PKG通路在二氧化硫（SO2）诱导的血管舒张中的作用。结果表明，SO_2浓度依赖性地舒张苯丙氨酸（PE）预收缩的大鼠主动脉环，并伴随cGMP浓度的增加，而SO_2合酶抑制剂L-天冬氨酸-β-异羟肟酸（HDX）则呈剂量依赖性地收缩主动脉环。用sGC抑制剂ODQ（30 μM）预处理主动脉环可减弱SO2的血管舒张作用，表明cGMP途径参与了SO2诱导的血管舒张。SO2上调sGC和PKG二聚体的蛋白水平，而HDX抑制它，表明SO2可以通过激活sGC促进cGMP合成。巯基还原剂二硫苏糖醇（DTT）可显著抑制预收缩环中sGC和PKG的二聚化以及SO2诱导的血管舒张。此外，SO2降低磷酸二酯酶5型（PDE 5），cGMP特异性水解酶的活性，这意味着SO2通过抑制其水解升高cGMP浓度。因此，SO2至少部分通过促进sGC和PKG的二硫键依赖性二聚化，导致血管中sGC/cGMP/PKG途径活化来发挥其血管舒张作用。这些发现揭示了SO2调节血管张力的新的作用模式和机制。
The present study was designed to explore the role of soluble guanylate cyclase (sGC)/cyclic guanosine monophosphate (cGMP)/PKG pathway in sulfur dioxide (SO2)-induced vasodilation. We showed that SO2 induced a concentration-dependent relaxation of phenylephrine (PE)-precontracted rat aortic rings in association with an increase in cGMP concentration, whereas l-aspartic acid β-hydroxamate (HDX), an inhibitor of SO2 synthase, contracted rings in a dose-dependent manner. Pretreatment of aortic rings with the sGC inhibitor ODQ (30 μM) attenuated the vasodilatory effects of SO2, suggesting the involvement of cGMP pathway in SO2-induced vasodilation. Mechanistically, SO2 upregulated the protein levels of sGC and PKG dimers, while HDX inhibited it, indicating SO2 could promote cGMP synthesis through sGC activation. Furthermore, the dimerization of sGC and PKG and vasodilation induced by SO2 in precontracted rings were significantly prevented by thiol reductants dithiothreitol (DTT). In addition, SO2 reduced the activity of phosphodiesterase type 5 (PDE5), a cGMP-specific hydrolytic enzyme, implying that SO2 elevated cGMP concentration by inhibiting its hydrolysis. Hence, SO2 exerted its vasodilatory effects at least partly by promoting disulfide-dependent dimerization of sGC and PKG, resulting in an activated sGC/cGMP/PKG pathway in blood vessels. These findings revealed a new mode of action and mechanisms by which SO2 regulated the vascular tone.
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影响因子：
5
作者：
Sun, Yan;Tian, Yue;Du, Junbao
通讯作者：
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二氧化硫通过内皮依赖性和独立机制放松大鼠主动脉
影响因子：
2.1
作者：
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影响因子：
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作者：
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通讯作者：
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DOI：
10.1007/s00424-014-1441-2
发表时间：
2014-01
期刊：
Pflügers Archiv - European Journal of Physiology
影响因子：
--
作者：
Juan Liu;Zhengju Chen;L. Ye;Huixia Liu;D. Dou;Limei Liu;Xiaoxing Yu;Yuansheng Gao
通讯作者：
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影响因子：
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作者：
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通讯作者：
Du, Jun-bao