Human cytomegalovirus induces caspase-dependent apoptosis of megakaryocytic CHRF-288-11 cells by activating the JNK pathway
Human cytomegalovirus induces caspase-dependent apoptosis of megakaryocytic CHRF-288-11 cells by activating the JNK pathway
复制标题
人巨细胞病毒通过激活JNK途径诱导巨核细胞CHRF-288-11细胞凋亡
DOI：
10.1007/s12185-010-0560-6
复制
发表时间：
2010-05-01
影响因子：
2.1
通讯作者：
Han, Yifan
中科院分区：
文献类型：
--
作者：
Dou, Juan;Li, Xiaofeng;Han, Yifan
人类巨细胞病毒（HCMV）感染通常与新生儿和免疫功能低下患者发生的血小板减少症有关。然而，潜在的机制仍然难以捉摸。本研究旨在探讨 HCMV 感染对巨核细胞 CHRF-288-11 细胞活力的影响及其潜在机制。 RT-PCR测定HCMV立即早期基因1的mRNA表达和Western blot测定晚期HCMV基因pp65的蛋白表达表明CHRF-288-11细胞对HCMV感染敏感。 HCMV 感染通过剂量和时间依赖性方式的细胞凋亡降低 CHRF-288-11 细胞的活力。在 HCMV 处理的 CHRF-288-11 细胞中，caspase 3 和 c-Jun 末端激酶 (JNK) 信号通路均被激活。 z-DEVD-fmk（一种 caspase 抑制剂）和 SP600125（一种 JNK 抑制剂）分别显着阻止 HCMV 诱导的 CHRF-288-11 细胞死亡。此外，抑制 JNK 活性可以减少 HCMV 诱导的活性 caspase 3 的形成。有趣的是，抗病毒药物更昔洛韦和SP600125的共同应用可以协同阻止HCMV诱导的CHRF-288-11细胞死亡。总的来说，这些发现表明HCMV感染可能通过激活JNK信号通路诱导巨核细胞CHRF-288-11细胞发生caspase依赖性凋亡。
Human cytomegalovirus (HCMV) infection is usually implicated in thrombocytopenia occurring in newborns and immunocompromised patients. However, the underlying mechanisms remain elusive. This study was conducted to investigate the effects of HCMV infection on the viability of megakaryocytic CHRF-288-11 cells and the underlying mechanisms involved. RT-PCR for determining mRNA expression of HCMV immediate early gene 1 and Western blot for measuring protein expression of late HCMV gene pp65 showed that CHRF-288-11 cells were susceptible to HCMV infection. HCMV infection reduced the viability of CHRF-288-11 cells via apoptosis in a dose- and time-dependent manner. Both caspase 3 and c-Jun terminal kinase (JNK) signaling pathway were activated in the HCMV-treated CHRF-288-11 cells. z-DEVD-fmk (a caspase inhibitor) and SP600125 (a JNK inhibitor) significantly prevented the death of CHRF-288-11 cells induced by HCMV, respectively. Furthermore, inhibition of JNK activity could reduce the formation of active caspase 3 induced by HCMV. Interestingly, the co-application of antivirus drug ganciclovir and SP600125 synergistically prevented the death of CHRF-288-11 cells induced by HCMV. Collectively, these findings suggest that HCMV infection may induce the caspase-dependent apoptosis of megakaryocytic CHRF-288-11 cells by the activation of JNK signaling pathway.