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乙酰半胱氨酸通过非氧化形式白蛋白的再生来抑制血小板功能。

-Acetylcysteine Inhibits Platelet Function through the Regeneration of the Non-Oxidative Form of Albumin.

作者信息

Eligini Sonia, Porro Benedetta, Aldini Giancarlo, Colli Susanna, Banfi Cristina

机构信息

Centro Cardiologico Monzino I.R.C.C.S., 20138 Milan, Italy.

Dipartimento di Scienze Farmaceutiche, Università degli Studi di Milano, 20133 Milan, Italy.

出版信息

Antioxidants (Basel). 2022 Feb 23;11(3):445. doi: 10.3390/antiox11030445.

DOI:10.3390/antiox11030445
PMID:35326096
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8944739/
Abstract

-acetylcysteine (NAC) is able to break down protein disulfides, generating free thiols. This mechanism occurs on mixed disulfides of albumin (HSA) to form mercaptoalbumin (HMA), the main antioxidant species in the plasma. Circulating HSA exists in two main forms: the reduced form (HMA), and the oxidized forms, whose predominant modification is cystenylation (HSA-Cys). Increased levels of oxidized HSA have been detected in several diseases associated with oxidative stress. This study showed that NAC inhibits platelet aggregation by restoring HMA. In addition, the regeneration of HMA by NAC inhibits platelet functions such as intracellular calcium mobilization, reactive oxygen species generation, arachidonic acid metabolites synthesis, and adhesion to the collagen matrix. In our conditions, the exposure of platelets to NAC did not increase GSH levels. However, the inhibition of platelet aggregation was also detected following treatment of platelet-rich plasma with GSH, which, similarly to NAC, reduced HSA-Cys levels. Furthermore, this study showed that cysteine, another compound able to restore HMA by reducing the HSA-Cys content, inhibited platelet aggregation to a similar extent as NAC. The results obtained in this study suggest a new mechanism by which NAC can modulate platelet activation and suggest its possible use as an antiplatelet drug in conditions associated with oxidative stress.

摘要

乙酰半胱氨酸(NAC)能够分解蛋白质二硫键,生成游离巯基。这一机制发生在白蛋白(HSA)的混合二硫键上,形成血浆中的主要抗氧化物质巯基白蛋白(HMA)。循环中的HSA主要以两种形式存在:还原形式(HMA)和氧化形式,其主要修饰为半胱氨酸化(HSA-Cys)。在几种与氧化应激相关的疾病中,已检测到氧化型HSA水平升高。本研究表明,NAC通过恢复HMA来抑制血小板聚集。此外,NAC使HMA再生可抑制血小板功能,如细胞内钙动员、活性氧生成、花生四烯酸代谢物合成以及与胶原基质的黏附。在我们的实验条件下,血小板暴露于NAC并未增加谷胱甘肽(GSH)水平。然而,用GSH处理富血小板血浆后也检测到了血小板聚集的抑制,与NAC类似,GSH也降低了HSA-Cys水平。此外,本研究表明,另一种能够通过降低HSA-Cys含量来恢复HMA的化合物半胱氨酸,其抑制血小板聚集的程度与NAC相似。本研究获得的结果提示了一种NAC调节血小板活化的新机制,并表明其在与氧化应激相关的疾病中可能作为一种抗血小板药物使用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f2e/8944739/efe9acab5016/antioxidants-11-00445-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f2e/8944739/139604327283/antioxidants-11-00445-g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f2e/8944739/8c8c20b36f64/antioxidants-11-00445-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f2e/8944739/54cd91f609b3/antioxidants-11-00445-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f2e/8944739/e37385a30e4f/antioxidants-11-00445-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f2e/8944739/f2eaa35415df/antioxidants-11-00445-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f2e/8944739/f3e02a5a8ea5/antioxidants-11-00445-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f2e/8944739/efe9acab5016/antioxidants-11-00445-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f2e/8944739/139604327283/antioxidants-11-00445-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f2e/8944739/a7991b13e20f/antioxidants-11-00445-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f2e/8944739/8c8c20b36f64/antioxidants-11-00445-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f2e/8944739/54cd91f609b3/antioxidants-11-00445-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f2e/8944739/e37385a30e4f/antioxidants-11-00445-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f2e/8944739/f2eaa35415df/antioxidants-11-00445-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f2e/8944739/f3e02a5a8ea5/antioxidants-11-00445-g007.jpg
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