Herpes simplex virus type 1-induced encephalitis has an apoptotic component associated with activation of c-Jun N-terminal kinase.
Herpes simplex virus type 1-induced encephalitis has an apoptotic component associated with activation of c-Jun N-terminal kinase.
复制标题
单纯疱疹病毒 1 型诱发的脑炎具有与 c-Jun N 末端激酶激活相关的细胞凋亡成分。
DOI：
10.1080/13550280390173427
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发表时间：
2003
影响因子：
3.2
通讯作者：
Aurelian,Laure
中科院分区：
文献类型：
--
作者：
Perkins,Dana;Gyure,KymberlyA;Pereira,EdnaFR;Aurelian,Laure
单纯疱疹病毒 1 型 (HSV-1) 在海马培养物中引发细胞凋亡，通过末端脱氧核苷酸转移酶介导的 dUTP 缺口末端标记 (TUNEL) 和使用活化 caspase 3 大片段特异性抗体进行免疫组织化学测定。在 HSV-1 感染的海马培养物中，磷酸化（活化）c-Jun N 末端激酶 (JNK) 的水平也增加，磷酸化（活化）c-Jun N 末端激酶 (JNK) 的水平也增加。激活的c-Jun，它的目标。 JNK 抑制剂 SP600125 抑制细胞凋亡证明，JNK 激活参与了 HSV-1 诱导的细胞凋亡。 HSV-2 激活丝裂原激活蛋白激酶/细胞外调节蛋白激酶 (MEK/ERK) 存活途径，并且不会引发海马培养物中的细胞凋亡。 MEK特异性抑制剂U0126抑制ERK激活，并导致HSV-2感染培养物中TUNEL+细胞百分比显着增加，表明HSV-2未能触发细胞凋亡是由于其激活MEK/ERK存活途径的能力。 HSV-1 抗原呈阳性的 HSV 相关急性局灶性脑炎 (HSE) 患者的脑组织中 JNK 也被激活。 JNK 激活与细胞凋亡相关，通过使用激活的 caspase 3 或裂解聚 (ADP-核糖) 聚合酶 (PARP) 的抗体进行免疫组织化学测定。数据表明，HSE 具有可能有助于疾病发病机制的细胞凋亡成分。
Herpes simplex virus type 1 (HSV-1) triggered apoptosis in hippocampal cultures, as determined by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) and immunohistochemistry with antibody specific for the large fragment of activated caspase 3. The levels of phosphorylated (activated) c-Jun N-terminal kinase (JNK) were also increased in HSV-1-infected hippocampal cultures as were the levels of activated c-Jun, its target. JNK activation was involved in HSV-1-induced apoptosis as evidenced by apoptosis inhibition with the JNK inhibitor SP600125. HSV-2 activated the mitogen-activated protein kinase/extracellular regulated protein kinase (MEK/ERK) survival pathway and did not trigger apoptosis in hippocampal cultures. The MEK specific inhibitor U0126 inhibited ERK activation and caused a significant increase in the percent TUNEL+ cells in HSV-2-infected cultures, indicating that the failure of HSV-2 to trigger apoptosis is due to its ability to activate the MEK/ERK survival pathway. JNK was also activated in brain tissues from patients with HSV-associated acute focal encephalitis (HSE) that were positive for HSV-1 antigen. JNK activation correlated with apoptosis, as determined by immunohistochemistry with antibody to activated caspase 3 or cleaved poly (ADP-ribose) polymerase (PARP). The data suggest that HSE has an apoptotic component that may contribute to disease pathogenesis.