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同型半胱氨酸及其硫内酯刺激引起的人血浆蛋白修饰是否会在体外诱导血浆止血功能的变化?

May modifications of human plasma proteins stimulated by homocysteine and its thiolactone induce changes of hemostatic function of plasma in vitro?

作者信息

Olas Beata, Kołodziejczyk Joanna, Malinowska Joanna

机构信息

Department of General Biochemistry, Institute of Biochemistry, University of Łódź, Banacha 12/16, 90-237 Łódź, Poland.

出版信息

Gen Physiol Biophys. 2010 Jun;29(2):186-93. doi: 10.4149/gpb_2010_02_186.

Abstract

Homocysteine (Hcys) may be implicated in different diseases, especially in cardiovascular illnesses. The most reactive form of Hcys is its cyclic thioester-homocysteine thiolactone (HTL), which is formed in plasma and represents up to 0.29% of plasma total Hcys. Recently, it has been observed that Hcys and HTL may modify plasma proteins, including albumin, hemoglobin or fibrinogen, but the role of this process is not yet well known. The aim of our study in vitro was to investigate the modifications of human plasma total proteins after incubation with the reduced form of Hcys in concentrations 10-100 micromol/l, and HTL in concentrations 1-0.1 micromol/l, which correspond to levels found in human plasma during hyperhomocysteinemia in vivo. The aim of our study was also to explain the effects of Hcys and HTL on coagulation activity of human plasma. We showed that in model system in vitro Hcys and HTL change the level of thiol, amino and carbonyl groups in plasma total proteins. Moreover, our studies reported that not only Hcys (10-100 micromol/l), but also HTL (at lower concentrations than Hcys) modulates the coagulation properties of human plasma.

摘要

同型半胱氨酸(Hcys)可能与多种疾病有关,尤其是心血管疾病。Hcys最具反应活性的形式是其环状硫酯——同型半胱氨酸硫内酯(HTL),它在血浆中形成,占血浆总Hcys的0.29%。最近,有人观察到Hcys和HTL可能会修饰血浆蛋白,包括白蛋白、血红蛋白或纤维蛋白原,但这一过程的作用尚不清楚。我们体外研究的目的是探讨在体外分别用浓度为10 - 100微摩尔/升的还原型Hcys和浓度为1 - 0.1微摩尔/升的HTL孵育人血浆总蛋白后的变化,这些浓度与体内高同型半胱氨酸血症时人体血浆中的水平相对应。我们研究的目的还包括解释Hcys和HTL对人血浆凝血活性的影响。我们发现,在体外模型系统中,Hcys和HTL会改变血浆总蛋白中巯基、氨基和羰基的水平。此外,我们的研究报告称,不仅Hcys(10 - 100微摩尔/升),而且HTL(浓度低于Hcys)也会调节人血浆的凝血特性。

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