Human hepatitis C virus NS5A protein alters intracellular calcium levels, induces oxidative stress, and activates STAT-3 and NF-κB
Human hepatitis C virus NS5A protein alters intracellular calcium levels, induces oxidative stress, and activates STAT-3 and NF-κB
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DOI：
10.1073/pnas.171311298
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发表时间：
2001-08-14
影响因子：
11.1
通讯作者：
Siddiqui, A
中科院分区：
文献类型：
--
作者：
Gong, GZ;Waris, G;Siddiqui, A
由人丙型肝炎病毒RNA基因组编码的非结构蛋白5A（NS 5A）在此显示通过氧化应激诱导NF-κ B和STAT-3转录因子从其胞质驻留物活化。NS 5A引起细胞内钙离子紊乱。Ca 2+信号转导触发线粒体中活性氧的升高，导致NF-κ B和STAT-3易位到细胞核中。有证据表明STAT-3被NS 5A组成性激活。在抗氧化剂[吡咯烷二硫代氨基甲酸酯（PDTC），N-乙酰L-半胱氨酸（NAC）]或Ca 2+螯合剂（EGTA-AM，TMB-8）的存在下，NS 5A诱导的NF-κ B和STAT-3活化被消除。这些结果提供了对NS 5A可以改变与病毒感染相关的肝脏发病机制相关的细胞内事件的机制的深入了解。
The nonstructural protein 5A (NS5A) encoded by the human hepatitis C virus RNA genome is shown here to induce the activation of NF-kappaB and STAT-3 transcription factors from its cytoplasmic residence via oxidative stress. NS5A causes the disturbance of intracellular calcium. Ca2+ signaling triggers the elevation of reactive oxygen species in mitochondria, leading to the translocation of NF-KB and STAT-3 into the nucleus. Evidence is presented for the constitutive activation of STAT-3 by NS5A. In the presence of antioxidants [pyrrolidine dithiocarbamate (PDTC), N-acetyl L-cysteine (NAC)] or Ca2+ chelators (EGTA-AM, TMB-8), NS5A-induced activation of NF-kappaB and STAT-3 was eliminated. These results provide an insight into the mechanism by which NS5A can alter intracellular events relevant to liver pathogenesis associated with the viral infection.