Hydrogen peroxide-induced apoptosis is CD95-independent, requires the release of mitochondria-derived reactive oxygen species and the activation of NF-κB
Hydrogen peroxide-induced apoptosis is CD95-independent, requires the release of mitochondria-derived reactive oxygen species and the activation of NF-κB
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DOI：
10.1038/sj.onc.1202325
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发表时间：
1999-01-21
期刊：
影响因子：
8
通讯作者：
Schmitz, ML
中科院分区：
文献类型：
--
作者：
Dumont, A;Hehner, SP;Schmitz, ML
活性氧(ROS)在多种不同刺激诱导的细胞死亡中起重要作用。本研究表明，过氧化氢诱导的T细胞凋亡不需要酪氨酸激酶p56(Lck)、磷酸酶CD45、CD95受体及其相关的Caspase-8，过氧化氢诱导的细胞死亡导致Caspase-3的裂解和激活，过氧化氢处理T细胞导致线粒体通透性转换孔的形成，线粒体跨膜电位Delta Psi(M)迅速降低和细胞色素C的释放，bongkrekic酸(BA)抑制线粒体通透性转换，鱼藤酮或甲萘二酮干扰线粒体电子传递系统，阻止H_2O_2、抗霉素A、甲萘二酮的细胞毒性作用一种线粒体抑制剂，增加线粒体ROS(MIROS)的释放，促进细胞凋亡。Bcl2和病毒抗凋亡蛋白BHRF-1和E1B19K的过表达可拮抗过氧化氢诱导的细胞凋亡，转录因子NF-kappa B的药理和遗传抑制可保护细胞免受过氧化氢诱导的细胞死亡。核因子-kappa B介导过氧化氢诱导的细胞死亡的这种有害作用可能依赖于死亡效应基因的诱导表达，如P53，它是在过氧化氢存在下依赖于核因子-kappa B上调的。
Reactive oxygen species (ROS) play an important role in cell death induced by many different stimuli. This study shows that hydrogen peroxide-induced apoptosis in T-cells did not require tyrosine kinase p56(lck), phosphatase CD45, the CD95 receptor and its associated Caspase-8, H2O2-triggered cell death led to the induced cleavage and activation of Caspase-3, Hydrogen peroxide-treatment of T-cells resulted in the formation of mitochondrial permeability transition pores, a rapid decrease of the mitochondrial transmembrane potential Delta Psi(m) and the release of Cytochrome C, Inhibition of the mitochondrial permeability transition by bongkrekic acid (BA), or interference with the mitochondrial electron transport system by rotenone or menadione prevented the cytotoxic effect of H2O2, Antimycin A, a mitochondrial inhibitor that increases the release of mitochondrial ROS (MiROS), enhanced apoptosis. Overexpression of Bcl-2 and the viral anti-apoptotic proteins BHRF-1 and E1B 19K counteracted H2O2-induced apoptosis, Pharmacological and genetic inhibition of transcription factor NF-kappa B protected cells from hydrogen peroxide-elicited cell death. This detrimental effect of NF-kappa B mediating hydrogen peroxide-induced cell death presumably relies on the induced expression of death effector genes such as p53, which was NF-kappa B-dependently upregulated in the presence of H2O2.