Apoptosis-inducing factor mediates microglial and neuronal apoptosis caused by pneumococcus
Apoptosis-inducing factor mediates microglial and neuronal apoptosis caused by pneumococcus
复制标题
DOI：
10.1086/324013
复制
发表时间：
2001-11-15
影响因子：
6.4
通讯作者：
Cleveland, JL
中科院分区：
文献类型：
--
作者：
Braun, JS;Novak, R;Cleveland, JL
肺炎链球菌是细菌性脑膜炎的主要病因，它通过诱导神经元凋亡而损害海马。阻断半胱天冬酶仅在实验性脑膜炎中提供部分保护，这表明存在额外的凋亡途径。这一途径的一个触发因素是细菌本身，因为小胶质细胞或神经元暴露于活的肺炎球菌会诱导快速凋亡。在本研究中，凋亡与caspase -1-10的激活无关，并且不受广谱caspase抑制剂z-VAD-fmk的抑制。相反，细胞凋亡归因于线粒体损伤，随后线粒体释放凋亡诱导因子（AIF），大规模DNA断裂和次二倍体。此外，胞浆内微量注射aif特异性抗血清可显著损害肺炎球菌诱导的细胞凋亡。这些发现表明AIF可能在脑细胞凋亡和细菌发病中起核心作用。
Streptococcus pneumoniae is the major cause of bacterial meningitis and it damages the hippocampus by inducing neuronal apoptosis. The blocking of caspases provides only partial protection in experimental meningitis, which suggests that there is an additional apoptotic pathway. A trigger of this pathway is the bacterium itself, as exposure of microglia or neurons to live pneumococci induces rapid apoptosis. In this study, apoptosis was not associated with the activation of caspases-1-10 and was not inhibited by z-VAD-fmk, a broad-spectrum caspase inhibitor. Rather, apoptosis was attributed to damage to mitochondria, which was followed by the release of apoptosis-inducing factor (AIF) from the mitochondria, large-scale DNA fragmentation, and hypodiploidy. Furthermore, intracytoplasmatic microinjection of AIF-specific antiserum markedly impaired pneumococcus-induced apoptosis. These findings indicate that AIF may play a central role in brain cell apoptosis and bacterial pathogenesis.