Norswertianolin Promotes Cystathionine γ-Lyase Activity and Attenuates Renal Ischemia/Reperfusion Injury and Hypertension.
Norswertianolin Promotes Cystathionine γ-Lyase Activity and Attenuates Renal Ischemia/Reperfusion Injury and Hypertension.
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Norswertianolin 促进胱硫醚γ-裂解酶活性并减轻肾缺血/再灌注损伤和高血压
DOI：
10.3389/fphar.2021.677212
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发表时间：
2021
影响因子：
5.6
通讯作者：
Geng B
中科院分区：
文献类型：
--
作者：
Niu Y;Du C;Cui C;Zhang H;Deng Y;Cai J;Chen Z;Geng B
胱硫醚γ-裂解酶（CSE）/硫化氢（H2S）在心血管疾病包括高血压和缺血/再灌注（I/R）损伤中起保护作用。本研究旨在筛选激活CSE活性的天然小分子化合物，然后评价其对肾I/R损伤和高血压的影响。应用计算机分子对接技术，筛选出与CSE特异性结合的天然小分子化合物去甲獐牙菜苷（NW）。利用微量热电泳技术，我们证实了Leu 68位点是NW与CSE结合的必要氢键位点。NW补充显着增加CSE的表达和其活性的H2S生成在体内和体外。在急性和长期肾I/R损伤模型中，NW预处理显著减轻肾损伤，与降低血尿素氮（BUN）、血清肌酐（Cr）水平、活性氧（ROS）产生和切割的caspase 3表达相关。在自发性高血压大鼠（SHR）中，NW治疗还降低了血压、股动脉中膜/管腔比以及炎症细胞因子的mRNA水平。结论：NW是一种新型的CSE小分子化合物激动剂，可直接与CSE结合，提高CSE产生H2S的活性，从而减轻肾I/R损伤和高血压。NW对心血管疾病具有潜在的治疗价值。
Cystathionine gamma-lyase (CSE)/hydrogen sulfide (H2S) plays a protective role in cardiovascular diseases including hypertension and ischemia/reperfusion (I/R) injury. This study was aimed to screen natural small molecule compounds that activate CSE activity and then evaluate its effect(s) on kidney I/R injury and hypertension. Applying computer molecular docking technology, we screened the natural small molecule compound norswertianolin (NW)-specific binding to CSE. Using the microscale thermophoresis technology, we confirmed that the Leu68 site was the essential hydrogen bond site of NW binding to CSE. NW supplementation significantly increased CSE expression and its activity for H2S generation both in vivo and in vitro. In the model of acute and long-term kidney I/R injury, NW pretreatment dramatically attenuated kidney damage, associated with decreasing blood urea nitrogen (BUN), serum creatinine (Cr) level, reactive oxygen species (ROS) production, and cleaved caspase 3 expression. In spontaneously hypertensive rats (SHRs), NW treatment also lowered blood pressure, the media/lumen ratio of the femoral artery, and the mRNA level of inflammatory cytokines. In conclusion, NW acts as a novel small molecular chemical compound CSE agonist, directly binding to CSE, heightening CSE generation–H2S activity, and then alleviating kidney I/R injury and hypertension. NW has a potential therapeutic merit for cardiovascular diseases.
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H2S 供体 NaHS 改变心肌梗死后 H2S 产生酶的表达模式
影响因子：
--
作者：
Li, Na;Wang, Ming-Jie;Zhu, Yi-Chun
通讯作者：
Zhu, Yi-Chun
影响因子：
3
作者：
Ahmad, Fiaz Ud Din;Sattar, Munavvar Abdul;Johns, Edward James
通讯作者：
Johns, Edward James
DOI：
10.1161/atvbaha.118.311229
发表时间：
2018-09
期刊：
Arteriosclerosis, thrombosis, and vascular biology
影响因子：
--
作者：
Brown IAM;Diederich L;Good ME;DeLalio LJ;Murphy SA;Cortese-Krott MM;Hall JL;Le TH;Isakson BE
通讯作者：
Isakson BE
影响因子：
2.1
作者：
Azizi, F.;Seifi, B.;Ahghari, P.
通讯作者：
Ahghari, P.
影响因子：
13.6
作者：
Bos, Eelke M.;Leuvenink, Henri G. D.;van Goor, Harry
通讯作者：
van Goor, Harry