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首页> 外文期刊>Platelets >Thiosulfinates modulate platelet activation by reaction with surface free sulfhydryls and internal thiol-containing proteins.
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Thiosulfinates modulate platelet activation by reaction with surface free sulfhydryls and internal thiol-containing proteins.

机译：硫代亚磺酸盐通过与表面游离巯基和内部含巯基的蛋白质反应来调节血小板活化。

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Thiosulfinates are characteristic flavors of Allium vegetables, with a highly reactive S-S=O group, that we previously showed to inhibit platelet aggregation through calpain-dependent mechanisms. With the aim to clarify the mode of action of these redox phytochemicals, we studied their effect on extracellular free sulfhydryls in relation to their effect on platelet responses (Ca2+ signals, release reaction, and aIIb3 integrin activation state). At the platelet surface, thiosulfinate dose-dependently increased the basal level of free sulfhydryls, independently of protein disulfide isomerase activity. This generation of new free sulfhydryls was associated with: (i) a three fold increase in labeling of resting platelets with an anti ligand-induced binding site antibody and (ii) marked inhibition of subsequent aIIb3 activation by agonists. Thiosulfinates increased the basal intracellular Ca2+ level of platelets. In activated platelets, they markedly inhibited the Ca2+ mobilization independently of the external Ca2+, the calpain-induced SNAP-23 cleavage and the granule release. In platelet free systems, thiosulfinates inhibited the activity of purified calpain and the free sulfhydryl of glutathione without any reducing properties on disulfides. The results demonstrate for the first time that thiosulfinates rapidly interact with sulfhydryls both at the platelet surface and inside the cell on intracellular cysteine-proteins, especially calpain. Inhibition of free cysteine and glutathione in whole blood may also contribute to their anti-aggregant properties. Such sulfur compounds are of interest for the development of a new class of antithrombotic agents.
机译：硫代亚硫酸盐是葱属蔬菜的特征性风味，具有高反应性的S-S = O基团，我们先前已证明其通过钙蛋白酶依赖性机制抑制血小板聚集。为了阐明这些氧化还原植物化学物质的作用方式，我们研究了它们对细胞外游离巯基的影响与它们对血小板反应（Ca2 +信号，释放反应和aIIb3整联蛋白激活状态）的影响有关。在血小板表面，硫代亚磺酸盐剂量依赖性地增加了游离巯基的基础水平，而与蛋白质二硫键异构酶活性无关。这种新的游离巯基的产生与：（i）用抗配体诱导的结合位点抗体标记静止血小板的标记增加了三倍，以及（ii）激动剂对随后的aIIb3激活的明显抑制。硫代亚磺酸盐增加了血小板的基础细胞内Ca2 +水平。在活化的血小板中，它们显着抑制Ca2 +动员，而与外部Ca2 +，钙蛋白酶诱导的SNAP-23裂解和颗粒释放无关。在无血小板系统中，硫代亚磺酸盐抑制了纯化的钙蛋白酶的活性和谷胱甘肽的游离巯基，而对二硫化物没有任何还原性。结果首次证明了硫亚磺酸盐在细胞内半胱氨酸蛋白（尤其是钙蛋白酶）的血小板表面和细胞内部均与巯基快速相互作用。全血中游离半胱氨酸和谷胱甘肽的抑制也可能有助于它们的抗凝集特性。这类硫化合物对于开发新型抗血栓剂是令人感兴趣的。

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