Hydrogen sulfide mediates the vasoactivity of garlic
Hydrogen sulfide mediates the vasoactivity of garlic
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DOI：
10.1073/pnas.0705710104
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发表时间：
2007-11-13
影响因子：
11.1
通讯作者：
Kraus, David W.
中科院分区：
文献类型：
--
作者：
Benavides, Gloria A.;Squadrito, Giuseppe L.;Kraus, David W.
大蒜的消费与心血管疾病的进展呈负相关，尽管其机制尚不清楚。本研究表明，人红细胞将大蒜衍生的有机多硫化物转化为硫化氢（H2S），这是一种内源性的心脏保护血管细胞信号分子。这种H2S的产生，通过一种新型的极谱H2S传感器实时测量，由葡萄糖维持的胞质谷胱甘肽水平支持，并且在很大程度上依赖于红细胞膜内或膜上的还原硫醇。烯丙基取代基和拴链硫原子数量的增加促进了有机多硫化物产生H2S。烯丙基取代的多硫化物在烯丙基取代基的a碳上发生亲核取代，从而形成氢多硫化物（RSnH），这是形成H2S的关键中间体。有机多硫化物（R-Sn-R′；n >2）也在硫原子上发生亲核取代，生成RSnH和H2S。在生理相关的氧水平下，完整的主动脉环也会代谢大蒜衍生的有机多硫化物，释放H2S。大蒜化合物的血管活性与H2S的产生是同步的，它们介导松弛的效力随着H2S的产生而增加，这有力地支持了我们关于H2S介导大蒜血管活性的假设。我们的研究结果还表明，产生H2S的能力可以用来标准化大蒜膳食补充剂。
The consumption of garlic is inversely correlated with the progression of cardiovascular disease, although the responsible mechanisms remain unclear. Here we show that human RBCs convert garlic-derived organic polysulfides into hydrogen sulfide (H2S), an endogenous cardioprotective vascular cell signaling molecule. This H2S production, measured in real time by a novel polarographic H2S sensor, is supported by glucose-maintained cytosolic glutathione levels and is to a large extent reliant on reduced thiols in or on the RBC membrane. H2S production from organic polysulfides is facilitated by allyl substituents and by increasing numbers of tethering sulfur atoms. Allyl-substituted polysulfides undergo nucleophilic substitution at the a carbon of the allyl substituent, thereby forming a hydropolysulfide (RSnH), a key intermediate during the formation of H2S. Organic polysulfides (R-Sn-R'; n > 2) also undergo nucleophilic substitution at a sulfur atom, yielding RSnH and H2S. Intact aorta rings, under physiologically relevant oxygen levels, also metabolize garlic-derived organic polysulfides to liberate H2S. The vasoactivity of garlic compounds is synchronous with H2S production, and their potency to mediate relaxation increases with H2S yield, strongly supporting our hypothesis that H2S mediates the vasoactivity of garlic. Our results also suggest that the capacity to produce H2S can be used to standardize garlic dietary supplements.