Human endogenous retrovirus W family envelope gene activates the small conductance Ca2+-activated K+ channel in human neuroblastoma cells through CREB
Human endogenous retrovirus W family envelope gene activates the small conductance Ca2+-activated K+ channel in human neuroblastoma cells through CREB
复制标题
DOI：
10.1016/j.neuroscience.2013.05.033
复制
发表时间：
2013-09
期刊：
影响因子：
3.3
通讯作者：
S. Li;Z. Liu;S. Yin;Y. T. Chen;H. Yu;J. Zeng;Q. Zhang;F. Zhu
中科院分区：
文献类型：
--
作者：
S. Li;Z. Liu;S. Yin;Y. T. Chen;H. Yu;J. Zeng;Q. Zhang;F. Zhu
大量研究表明，人类内源性逆转录病毒W家族（HERV-W）包膜基因（env）与多种疾病有关，但其机制尚不清楚。本实验室前期研究发现，精神分裂症患者血清中存在HERV-W env的异常表达。在本文中，我们报道了HERV-W env的过表达升高了人神经母细胞瘤细胞中小电导钙激活K+通道蛋白3（SK 3）的水平。利用荧光素酶报告系统和RNA干扰方法，我们发现HERV-W env启动SK 3基因表达需要功能性cAMP反应元件位点。此外，还发现SK 3通道被HERV-W env激活。进一步的研究表明，cAMP反应元件结合蛋白（CREB）是激活SK 3通道所必需的。因此，提出了HERV-W env如何影响神经元活动并导致精神疾病如精神分裂症的新信号传导机制。
Numerous studies have shown that human endogenous retrovirus W family (HERV-W) envelope gene (env) is related to various diseases but the underlying mechanism has remained poorly understood. Our previous study showed that there was abnormal expression of HERV-W env in sera of patients with schizophrenia. In this paper, we reported that overexpression of the HERV-W env elevated the levels of small conductance Ca2+-activated K+channel protein 3 (SK3) in human neuroblastoma cells. Using a luciferase reporter system and RNA interference method, we found that functional cAMP response element site was required for the expression of SK3 triggered by HERV-W env. In addition, it was also found that the SK3 channel was activated by HERV-W env. Further study indicated that cAMP response element-binding protein (CREB) was required for the activation of the SK3 channel. Thus, a novel signaling mechanism of how HERV-W env influences neuronal activity and contributes to mental illnesses such as schizophrenia was proposed.