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终末期肾衰竭患者血浆中硫醇稳态的破坏。

Disruption of thiol homeostasis in plasma of terminal renal failure patients.

作者信息

Włodek Przemysław J, Smolenski Olgierd B, Chwatko Grazyna, Iciek Małgorzata B, Miłkowski Andrzej, Bald Edward, Włodek Lidia

机构信息

Department of Nephrology, Rydygier Hospital, os. Złotej Jesieni 1, 31-826 Cracow, Poland.

出版信息

Clin Chim Acta. 2006 Apr;366(1-2):137-45. doi: 10.1016/j.cca.2005.09.028. Epub 2005 Dec 7.

Abstract

BACKGROUND

The aim of the present studies was to investigate the changes in concentrations of different forms of thiols in plasma of terminal renal failure patients before and after hemodialysis.

METHODS

Total concentrations of thiols, their free forms and the level of their mixed disulfides with proteins were determined with HPLC.

RESULTS

In terminal renal failure patients before dialysis, total concentrations of cysteine, homocysteine and cysteinylglycine and their free and protein-bound fractions increased while level of all such forms of glutathione dropped. A single dialysis session caused short-lasting return of concentrations of all forms of thiols to the level equal or close to the control group. The changes observed in non-dialyzed patients were similar to those observed in dialyzed patients before single dialysis procedure.

CONCLUSIONS

The obtained results showed severe disturbance of thiol homeostasis in plasma of terminal renal failure patients. The following changes have to be emphasized: (1) high level of free cysteine (cystine) fraction, (2) strong tendency of homocysteine to form mixed disulfides with proteins, (3) drop of glutathione level. These observations confirm a suggestion that atherogenic action of homocysteine can be a result of S-homocysteinylation and N-homocysteinylation reactions, whereas toxic action of cysteine can result from auto-oxidation reaction.

摘要

背景

本研究的目的是调查终末期肾衰竭患者血液透析前后血浆中不同形式硫醇浓度的变化。

方法

采用高效液相色谱法测定硫醇的总浓度、其游离形式以及与蛋白质形成的混合二硫键的水平。

结果

在透析前的终末期肾衰竭患者中,半胱氨酸、同型半胱氨酸和半胱氨酰甘氨酸的总浓度及其游离和与蛋白质结合的部分增加,而所有这些形式的谷胱甘肽水平下降。单次透析使所有形式硫醇的浓度短暂恢复到等于或接近对照组的水平。未透析患者中观察到的变化与单次透析前透析患者中观察到的变化相似。

结论

所得结果表明终末期肾衰竭患者血浆中硫醇稳态严重紊乱。必须强调以下变化:(1)游离半胱氨酸(胱氨酸)部分水平高,(2)同型半胱氨酸与蛋白质形成混合二硫键的强烈倾向,(3)谷胱甘肽水平下降。这些观察结果证实了一种观点,即同型半胱氨酸的致动脉粥样硬化作用可能是S-同型半胱氨酸化和N-同型半胱氨酸化反应的结果,而半胱氨酸的毒性作用可能源于自氧化反应。

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