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氯通道相关(RCLCA)分子在生理和病理状态下如何分布在唾液腺(主要是颌下腺)中。RCLCA定位于细胞质细胞器，即ER、高尔基体、早期和晚期内体等。艾尔。导管系统的。在涎腺导管系统中，纹状管和颗粒曲管中rCLCA的表达最强，而插入管和排泄管中的rCLCA含量较弱，浆液性和粘液性腺泡细胞中未检测到rCLCA。上述导管系统的rCLCA分子与其他氯离子通道分子如CFTR共定位。利用分子生物学(siRNA抑制信使核糖核酸的合成)、电生理学、药理学和生物化学等方法学方法，对rCLCA的功能进行了分析。随后，rCLCA和CFTR的相互作用以及rCLCA对涎腺导管系统离子转运的影响被部分阐明，并发表在国际期刊上。异丙肾上腺素诱导腺泡细胞增殖时，rCLCA的表达被显著抑制；几乎所有的rCLCA蛋白都消失了，除了插入的导管。与未表达rCLCA的细胞相比，稳定表达rCLCA的细胞株在加入Stauroporine后，细胞增殖活性降低，细胞凋亡率增加，rCLCA在生理和病理状态下的其他功能有待进一步研究。