S-Nitrosoglutathione Reductase Underlies the Dysfunctional Relaxation to Nitric Oxide in Preterm Labor.
S-Nitrosoglutathione Reductase Underlies the Dysfunctional Relaxation to Nitric Oxide in Preterm Labor.
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DOI：
10.1038/s41598-018-23371-w
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发表时间：
2018-04-04
影响因子：
4.6
通讯作者：
Buxton ILO
中科院分区：
文献类型：
--
作者：
Barnett SD;Smith CR;Ulrich CC;Baker JE;Buxton ILO
宫缩抑制剂对预防早产的效果有限。在子宫平滑肌中，cGMP积累后，添加一氧化氮（NO）对松弛的影响很小，这表明蛋白质S-亚硝化的作用。在来自足月分娩（TL）或早产自发分娩（sPTL）的妇女的人子宫肌层组织中，直接刺激可溶性鸟苷酸环化酶（sGC）不能松弛子宫肌层，而相同的治疗完全松弛血管平滑肌。与足月子宫肌层不同，NO的作用不仅在sPTL中减弱，而且整体蛋白S-亚硝化也减弱，表明对NO介导的蛋白S-亚硝化的功能障碍反应。内源性S-亚硝基谷胱甘肽可用性的酶调节剂S-亚硝基谷胱甘肽还原酶的检查揭示了与总蛋白S-亚硝化减少相关的早产子宫肌层中还原酶表达增加。阻断S-亚硝基谷胱甘肽还原酶可松弛sPTL组织。向肌动蛋白运动性测定中加入NO供体减弱了力。sGC激活介导sPTL组织松弛的失败，以及NO松弛TL而不是sPTL子宫肌层的能力，表明子宫肌层中NO介导松弛的独特途径。我们的研究结果表明，检查S-亚硝化对子宫平滑肌收缩调节的关键收缩相关蛋白的作用可以揭示新的宫缩抑制靶点。
Tocolytics show limited efficacy to prevent preterm delivery. In uterine smooth muscle cGMP accumulation following addition of nitric oxide (NO) has little effect on relaxation suggesting a role for protein S-nitrosation. In human myometrial tissues from women in labor at term (TL), or spontaneously in labor preterm (sPTL), direct stimulation of soluble guanylyl cyclase (sGC) fails to relax myometrium, while the same treatment relaxes vascular smooth muscle completely. Unlike term myometrium, effects of NO are not only blunted in sPTL, but global protein S-nitrosation is also diminished, suggesting a dysfunctional response to NO-mediated protein S-nitrosation. Examination of the enzymatic regulator of endogenous S-nitrosoglutathione availability, S-nitrosoglutathione reductase, reveals increased expression of the reductase in preterm myometrium associated with decreased total protein S-nitrosation. Blockade of S-nitrosoglutathione reductase relaxes sPTL tissue. Addition of NO donor to the actin motility assay attenuates force. Failure of sGC activation to mediate relaxation in sPTL tissues, together with the ability of NO to relax TL, but not sPTL myometrium, suggests a unique pathway for NO-mediated relaxation in myometrium. Our results suggest that examining the action of S-nitrosation on critical contraction associated proteins central to the regulation of uterine smooth muscle contraction can reveal new tocolytic targets.
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DOI：
10.1124/jpet.110.171934
发表时间：
2010-10-10
影响因子：
3.5
作者：
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DOI：
10.1080/10409238.2017.1304353
发表时间：
2017-06
影响因子：
6.5
作者：
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通讯作者：
Buxton ILO
影响因子：
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