Estrogen Regulation of a Ca2+ Activated Chloride Channel

雌激素对 Ca2 激活氯离子通道的调节

• 批准号: 6835262
• 负责人: CHI G ZHAO
• 金额: $ 2.77万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-06-28 至 2005-06-27
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6835262
• 关键词: astrocytes; biophysics; calcium flux; cell line; cell morphology; chloride channels; electrophysiology; estrogens; hormone regulation /control mechanism; membrane permeability; predoctoral investigator; protein kinase C; protein structure function; voltage /patch clamp; western blottings

DESCRIPTION (provided by applicant): Central nervous system injury triggers a response cascade leading to activation of astrocytes, which participate in post-traumatic brain swelling. Studies have shown that the hormone 17beta-estradiol (E2) plays an important role in CNS injury, in part because of its beneficial effects on astrocytes. A voltage-dependent Ca2+ activated CI- (CICa) channel that is involved in mediating cell swelling was recently identified in freshly isolated native reactive astrocytes. It was also found that this channel can be activated by E2. This project aims to explore the nongenomic signaling cascade induced by E2 during its activation of this channel. Based on a cell line of immortalized astrocytes expressing the CICa channel, and using patch clamp electrophysiology and Western immunoblot as the basic methods of investigation, various activators and inhibitors of PLC, IP3 and PKC will be employed to pharmacologically characterize and plot the E2--CICa signaling pathway in a stepwise fashion. Elucidating E2's protective mechanisms in astrocytes activated by traumatic injury will contribute to the understanding of CNS response to injury, and holds the prospect of improving therapy for the unfortunate patients who suffer from such injuries.

描述（由申请人提供）： 中枢神经系统损伤会触发反应级联反应导致星形胶质细胞的激活，该级联细胞参与创伤后脑肿胀。研究表明，激素17beta-雌二醇（E2）在中枢神经系统损伤中起重要作用，部分原因是它对星形胶质细胞的有益作用。最近在新鲜分离的天然反应性星形胶质细胞中鉴定出了介导细胞肿胀的电压依赖性Ca2+激活的CI-（CICA）通道。还发现该通道可以被E2激活。该项目旨在探索E2在该通道激活期间诱导的非原位信号传导级联。基于表达CICA通道的永生星形胶质细胞的细胞系，并使用斑块夹电生理学和西方免疫印迹作为基本研究方法，将使用PLC，IP3和PKC的各种激活剂和抑制剂，以在逐步时期进行药理表征和绘制E2--CICA信号途径。阐明由创伤性损伤激活的星形胶质细胞中E2的保护机制将有助于理解中枢神经系统对损伤的反应，并保持改善遭受此类伤害的不幸患者的治疗。