INVESTIGATION OF AN ALTERNATE CHLORIDE CONDUCTANCE IN CF

CF 中替代氯化物电导率的研究

• 批准号: 6207611
• 负责人: STEVEN Y CHANG
• 金额: $ 4.26万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-07-01 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6207611
• 关键词: antisense nucleic acid; apical membrane; calcium flux; calmodulin dependent protein kinase; cell line; chloride channels; chloride ion; cystic fibrosis; electrophysiology; epithelium; ion transport; membrane potentials; protein binding; protein protein interaction; protein structure function; site directed mutagenesis; voltage /patch clamp

Cystic Fibrosis is an ultimately fatal disease which involves multiple organ systems including the respiratory and gastrointestinal tracts. It also affects reproductive function. Patients tend to die from progressive lung disease which involves recurrent infections and obstruction. Central to its pathophysiology is a defect in ion transport. Specifically, there is a defect involving the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) which results in decreased chloride (Cl-) conductance across epithelia. It is possible that an alternate pathway for Cl- conductance may bypass the CFTR mediated defect. A promising candidate, CLC-3, may in fact, be the calcium dependent Cl- channel. There is evidence that CFTR regulates CLC-3. It may be possible to elucidate their relationship to each other via patch-clamp studies in transfected cell lines and in cell lines containing endogenous CFTR and CLC-3. Complimentary studies would involve antisense, mutagenesis and experiments examining protein-protein and domain-domain interactions.

囊性纤维化是一种最终致命疾病，涉及多个器官系统，包括呼吸道和胃肠道。它还影响生殖功能。患者倾向于死于涉及复发感染和阻塞的进行性肺部疾病。其病理生理学的核心是离子运输的缺陷。具体而言，存在涉及囊性纤维化跨膜电导调节剂（CFTR）的缺陷，该缺陷导致遍布上皮的氯化物（Cl-）电导降低。替代途径的替代途径可能绕过CFTR介导的缺陷。实际上，有希望的候选者CLC-3可能是钙依赖性的Cl-通道。有证据表明CFTR调节CLC-3。可以通过转染的细胞系以及含有内源性CFTR和CLC-3的细胞系中的斑块钳研究来阐明它们的关系。免费研究将涉及反义，诱变和检查蛋白质 - 蛋白质和结构域相互作用的实验。