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机构地区:[1]上海第二医科大学细胞生物学教研室,上海200025
出 处:《细胞生物学杂志》2005年第2期121-126,共6页Chinese Journal of Cell Biology
基 金:国家自然科学基金资助项目(No.30170475)~~
摘 要:氧化修饰是细胞内的活性氧诱导生物大分子发生氧化反应引起的结构及构象改变,发挥调控信号转导和对应激作出反应的功能。氧化修饰发生在凋亡信号转导中的多个生物大分子,包括凋亡相关蛋白质的氧化,如caspase-9、线粒体通透性转变孔及电压依赖的阴离子通道(voltage-dependent anion channel,VDAC),同时也包括膜磷脂的氧化修饰,如磷脂酰丝氨酸及线粒体特异的心磷脂。氧化修饰作用也涉及凋亡诱导因子、促凋亡的凋亡信号调控激酶1(apoptosis signal-regulating kinase1,ASK1)信号转导途径及抗凋亡的转录因子NF-κB的激活和活性。所以氧化修饰可能是调控凋亡信号转导机制中除磷酸化、泛素化外的另一个新的分子机制。Oxidative modification mainly refers to the structure and conformation alteration of macromol- ecules resulting from oxidative reaction induced by reactive oxygen species, which serves as a regulatory mecha- nism in cell signaling and responding to diverse stresses. Oxidative modifications occur in various macromolecules related of apoptosis signaling. Some proteins including caspase-9, mitochondria permeability transition pore and voltage-dependent anion channel, promote apoptosis once they are oxidized. Simultaneously, oxidation of phospho- lipids such as cardiclipin and phosphatidylserine also participate in apoptosis. In addition, oxidative modification function on the activation of apoptosis-inducing factor (AIF), on the regulation of apoptosis signal-regulating kinase 1(ASK1) signaling pathway and on the activation and activity of anti-apoptosis transcription factor NF-κB. Taken together, oxidative modification appears to be a pivotal modulating fashion and novel molecular mechanism in addition to phosphorylation and ubiquition in regulation of apoptotic signaling.
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