The localization of calcium-activated chloride channel and its contribution on related pathologic conditions

钙激活氯离子通道的定位及其对相关病理状况的贡献

• 批准号: 18592025
• 负责人: OKAMURA Kazuhiko
• 金额: $ 1.01万
• 依托单位: Fukuoka Dental College
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2006
• 资助国家: 日本
• 起止时间: 2006 至 2007
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18592025/
• 关键词: chloride channel; salivary gland; cancer cell; apoptosis; adhesion molecules; 局在; イオン組成; 顎下腺; 導管

This project clarified how rat calcium-activated chloride channel-related (rCLCA) molecules distribute in the salivary gland (chiefly submandibular gland) both at physiological and pathologic states. rCLCA was localizad throughout the cytoplasmic organellae, namely rER, Golgi apparatus, early and late endosomes, et. Al. of the ductal sytem. Within the salivary ductal system, striated ducts and granular convoluted tubules showed the most intense localization of rCLCA, while the amount of rCLCA weakened in intercalated ducts and excretory ducts, and no rCLCA was detected in the serous and mucinous acinar cells. rCLCA molecules at the above ductal system colocalized with other chloride channel molecules such as CFTR. The function of rCLCA was analyzed with broad methodological approaches as molecular biology (the inhibition of mRNA procuction with siRNA), electro-physiology, pharmacology and biochemistry along with co-workers. Subsequently the interaction of rCLCA and CFTR and the influence of rCLCA on ion transport of salivary ductal system were partially clarified, and these products were published in international journals.rCLCA expression was drastically depressed when the hyperplasia of acinar cells was induced by the isoproterenol administration; almost all rCLCA proteins disappeared except at the intercalated duct. Cell lines with stable rCLCAexpression showed decreased proliferative activity and increased apoptosis after the exposure of Staurosporine, compared with the same cell lines without rCLCAexpression.Further exploration would be required to elucidate the other function of rCLCA both in physiologic and pathlogic states.

该项目阐明了大鼠钙激活的氯化物通道（RCLCA）分子如何在生理和病理状态下分布在唾液腺（主要是下颌腺）中。 RCLCA是整个细胞质细胞器中的本地化，即RER，Golgi设备，早期和晚期内体等。 al。导管系统。在唾液导管系统中，横纹管和颗粒状的杂质小管显示出RCLCA的最强烈定位，而在插入的导管和排泄管道中弱的RCLCA量却弱，并且在浆液和粘膜细胞中未检测到RCLCA。上述导管系统与其他氯化物通道分子（如CFTR）共定位的RCLCA分子。用广泛的方法论方法分析了RCLCA的功能，作为分子生物学（用siRNA抑制mRNA的抑制），电生理学，药理学和生物化学以及同事。随后，RCLCA和CFTR的相互作用以及RCLCA对唾液导管系统离子运输的影响得到了部分阐明，并且这些产物在国际期刊中发表。当异丙肾上腺素施用诱导腺泡细胞的增生时，RCLCA表达急剧降低。除了插入的管道外，几乎所有RCLCA蛋白都消失了。与没有RCLCAExpression的相同细胞系相比，具有稳定的RCLCAETARMES的细胞系显示出增殖活性降低和凋亡增加。要阐明RCLCA在生理和路径状态下的其他功能。