Molecular nature of sulfhydryl modification by hydrogen peroxide on type 1 ryanodine receptor

作     者：Anthony F LAI 

作者机构：Cardiff CF14 4XN Cardiff University UK Wales Heart Research Institute Wales College of Medicine 

出 版 物：《Acta Pharmacologica Sinica》 (中国药理学报(英文版))

年 卷 期：2006年第27卷第7期

页      面：888-894页

核心收录：

学科分类：1007[医学-药学(可授医学、理学学位)] 1006[医学-中西医结合] 100706[医学-药理学] 1002[医学-临床医学] 100602[医学-中西医结合临床] 10[医学] 

基　　金：British Heart Foundation and Medical Research Council (to Anthony F LAI) 国家自然科学基金 国家教育部新世纪优秀人才支持计划 

主　　题：Ca2+ release channel/ryanodine receptor hydrogen peroxide reactive oxygen redoxsensitive ion channel 

摘      要：Aim:To elucidate the molecular nature of sulfhydryl modification by hydrogenperoxide on type 1 ryanodine receptor(RyR1).Methods:Rabbit skeletal musclesarcoplasmic reticulum was treated with hydrogen peroxide,then RyR1 complexwas *** proteins in the complex were analysed by electrophoresis,Western blot and electron ***:(1)Hydrogen peroxide inducesinter-subunit cross-linking within the tetrameric RyR1 molecule;(2)in parallel tointer-subunit cross-linking,the RyR1 molecule changes morphology;(3)the chemi-cal and morphological changes are reversible:upon reduction by reducing agents,the RyR1 molecule regains its original ***:These findings suggestthat the molecular mechanism of RyR1 channel activity in sarcoplasmic reticulumregulated by hydrogen peroxide is through inter-subunit cross-linking within thetetrameric RyR1 molecule,which in turn induces structural changes of RyR1.