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硫代乙酰胺诱导的肝性脑病期间脑膜结合型乙酰胆碱酯酶的动力学和热致性特性改变:与膜脂质变化的相关性

Alterations in kinetic and thermotropic properties of cerebral membrane-bound acetylcholineesterase during thioacetamide-induced hepatic encephalopathy: correlation with membrane lipid changes.

作者信息

Swapna I, SathyaSaikumar K V, Murthy Ch R K, Gupta A Dutta, Senthilkumaran B

机构信息

Department of Animal Sciences, School of Life Sciences, University of Hyderabad, Hyderabad, India.

出版信息

Brain Res. 2007 Jun 11;1153:188-95. doi: 10.1016/j.brainres.2007.02.095. Epub 2007 Mar 24.

DOI:10.1016/j.brainres.2007.02.095
PMID:17482580
Abstract

Acetylcholinesterase (AchE) is an important peripheral membrane-bound enzyme, crucial for cholinergic neurotransmission. Changes in AchE activity, kinetic and thermotropic properties were studied in hepatic encephalopathy (HE) associated with acute liver failure induced experimentally by the administration of the hepatotoxin thioacetamide (TAA). Activity of AchE decreased significantly following TAA administration. AchE from cerebral cortex membrane isolates of TAA-treated rats also showed a decrease in Vmax and an increase in Km. Arrhenius plots revealed considerable changes in the thermotropic behavior of AchE from membrane isolates obtained from TAA-treated rats as evident from the decreased transition temperature. A positive correlation was observed between changes in membrane cholesterol (r2=0.987), sphingomyelin (r2=0.99) levels and AchE activity, thus indicating that membrane lipid changes could underlie the observed changes in kinetic and thermotropic properties of membrane-bound AchE during TAA-induced HE.

摘要

乙酰胆碱酯酶(AchE)是一种重要的外周膜结合酶,对胆碱能神经传递至关重要。在通过给予肝毒素硫代乙酰胺(TAA)实验性诱导的急性肝衰竭相关的肝性脑病(HE)中,研究了AchE活性、动力学和热致性特性的变化。给予TAA后,AchE活性显著降低。来自TAA处理大鼠大脑皮质膜分离物的AchE也显示Vmax降低,Km增加。阿伦尼乌斯图显示,从TAA处理大鼠获得的膜分离物中AchE的热致性行为有相当大的变化,从降低的转变温度可以明显看出。观察到膜胆固醇(r2 = 0.987)、鞘磷脂(r2 = 0.99)水平变化与AchE活性之间存在正相关,因此表明膜脂质变化可能是TAA诱导的HE期间膜结合AchE的动力学和热致性特性所观察到变化的基础。

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