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Mechanism underlying impaired compartmentalization of AQP5 in parotid glands of diabetic rats and curative drug.

糖尿病大鼠腮腺 AQP5 区室化受损的机制及治疗药物。

基本信息

批准号：
15591968
负责人：
ISHIKAWA Yasuko
金额：
$ 2.24万
依托单位：
The University of Tokushima
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2004
项目状态：
已结题

项目摘要

Patients with diabetes mellitus who do not take xerogenic drugs often complain of dry-mouth symptoms, xerostomia. It remains unknown, however, whether aquaporin-5 (AQP5) is subjected to regulated trafficking in salivary gland cells of diabetic rats. In this study, we investigated the difference of subcellular localization of AQP5 in parotid glands of control and streptozocin-induced diabetic (diabetic) rats stimulated by the muscarinic agonist, cevimeline. Cevimeline induced an increase in the amount of AQP5 in the apical plasma membrane (APM) in parotid cells of control rats, but not diabetic rats. Immunohistochemical study indicated that AQP5 fluorescence, under unstimulated conditions, was colocalized with flotillin-2 and GM1 fluorescence in a diffuse pattern in the parotid cytoplasm of both control and diabetic rats. Ten minutes after intravenous injection of cevimeline, AQP5 fluorescence was dramatically increased together with flotillin-2 and GM1 fluorescence in the APM of the pa … More rotid cells of control rats, but not diabetic rats. Sixty minutes after the injection, there was diffuse pattern of fluorescence in the cytoplasm of control rats. The total amount of AQP5 did not decrease significantly in parotid cells of diabetic rats, but there was a significant increase in the amount of AQP5 mRNA in these cells. Administration of insulin to diabetic rats produced the cevimeline-induced trafficking of AQP5 with lipid rafts to the APM in parotid cells and the recovery of the amount of AQP5 mRNA in the cells, as observed in control rats. These findings indicate that AQP5 synthesis in rat parotid cells is not affected by diabetes mellitus at the translation step, but rather at the transcription step. Treatment of the parotid tissues with cevimeline for 10 min induced a decrease in the solubility of AQP5 by 1 % Triton X-100 in control rats, but not in diabetic rats, indicating that after trafficking with lipid rafts to the APM, AQP5 dissociates from lipid rafts to non-rafts in the APM in parotid cells. The results suggest that the impaired AQP5 translocation with lipid rafts to the APM in salivary gland cells in response to muscarinic agonists results in diabetic xerostomia. Less

糖尿病患者如果不服用致干燥药物，常出现口干症状。然而，水通道蛋白-5（AQP 5）在糖尿病大鼠唾液腺细胞中是否受调控运输仍不清楚。在这项研究中，我们研究了水通道蛋白5的亚细胞定位的差异，在腮腺的控制和链脲佐菌素诱导的糖尿病（糖尿病）大鼠刺激的毒蕈碱激动剂，西维美林。Cevimeline诱导对照大鼠腮腺细胞顶端质膜（APM）中AQP 5的量增加，但不诱导糖尿病大鼠。免疫组化研究表明，AQP 5的荧光，在未受刺激的条件下，共定位与flotilin-2和GM 1荧光在腮腺细胞质中的弥漫性模式的控制和糖尿病大鼠。静脉注射西维美林10分钟后，大鼠APM中AQP 5荧光显著增加，同时flotillin-2和GM 1荧光也显著增加。 ...更多信息对照组大鼠的甲状腺细胞，但糖尿病大鼠没有。注射后60分钟，对照组大鼠胞浆内可见弥漫性荧光。糖尿病大鼠腮腺细胞中AQP 5的总量没有明显减少，但这些细胞中AQP 5 mRNA的量显著增加。糖尿病大鼠胰岛素给药产生西维美林诱导的AQP 5与脂筏运输到腮腺细胞中的APM和细胞中的AQP 5 mRNA的量的恢复，如在对照大鼠中观察到的。这些发现表明，大鼠腮腺细胞中的AQP 5合成在翻译步骤中不受糖尿病的影响，而是在转录步骤中。用西维美林处理腮腺组织10 min可诱导对照大鼠中AQP 5在1%Triton X-100中的溶解度降低，但在糖尿病大鼠中则无此现象，表明在与脂筏一起运输至APM后，AQP 5在腮腺细胞中从脂筏解离为APM中的非脂筏。结果表明，受损的AQP 5易位与脂筏的APM在唾液腺细胞响应毒蕈碱激动剂的结果在糖尿病口干症。少