High-resolution molecular imaging to elucidate the mechanism of hearing loss due to connexin gene mutation

高分辨率分子成像阐明连接蛋白基因突变导致听力损失的机制

• 批准号: 16591720
• 负责人: SUZUKI Toshihiro
• 金额: $ 1.28万
• 依托单位: Kyoto Prefectural University of Medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2004
• 资助国家: 日本
• 起止时间: 2004 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-16591720/
• 关键词: spiral limbus; connexins; gap junctions; glucose; GLUT; tight junctions; 6-NBDG

To elucidate the role of the spiral limbus in glucose transport in the cochlea, we analyzed the expression and localization of GLUT1, connexin26, connexin30, and occludin in the spiral limbus of the rat cochlea. GLUT1 and occludin were detected in blood vessels. GLUT1, connexin26, connexin30, and occludin were also expressed in fibrocytes just basal to the supralimbal lining cells. Connexin26 and connexin30 were present among not only these GLUT1-positive fibrocytes but also GLUT1-negative fibrocytes. In vivo glucose imaging using 6-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-6- deoxyglucose (6-NBDG, MW 342) together with Evans Blue Albumin (EBA, MW 68,000) showed that 6-NBDG was rapidly distributed throughout the spiral limbus, whereas EBA was localized only in the vessels. Moreover, the gap junctional uncoupler heptanol inhibited the distribution of 6-NBDG. These findings suggest that gap junctions play an important role in glucose transport in the spiral limbus, i.e., that gap junctions mediate glucose transport from GLUT1-positive fibrocytes to GLUT1-negative fibrocytes in the spiral limbus.

为了阐明螺旋利姆布斯在耳蜗葡萄糖转运中的作用，我们分析了GLUT 1、连接蛋白26、连接蛋白30和闭合蛋白在大鼠耳蜗螺旋利姆布斯中的表达和定位。血管中检测到GLUT 1和occludin。GLUT 1，connexin 26，connexin 30和occludin也表达在纤维细胞只是基底缘上衬里细胞。连接蛋白26和连接蛋白30不仅存在于这些GLUT 1阳性纤维细胞中，而且存在于GLUT 1阴性纤维细胞中。使用6-[N-（7-硝基苯-2-氧杂-1，3-二氮唑-4-基）氨基]-6-脱氧葡萄糖（6-NBDG，MW 342）和伊文思蓝白蛋白（EBA，MW 68，000）进行的体内葡萄糖成像显示，6-NBDG迅速分布在整个螺旋利姆布斯中，而EBA仅局限于血管中。此外，差距连接解偶联剂庚醇抑制6-NBDG的分布。这些发现表明间隙连接在螺旋利姆布斯的葡萄糖转运中起重要作用，即，间隙连接介导葡萄糖从螺旋利姆布斯中的GLUT 1阳性纤维细胞转运到GLUT 1阴性纤维细胞。

项目成果

Gap junctions mediate glucose transport between GLUT1-positive and -negative cells in the spiral limbus of the rat cochlea

• DOI: 10.1080/15419060600631805
• 发表时间: 2006-01-01
• 期刊: CELL COMMUNICATION AND ADHESION
• 作者: Matsunami, T;Suzuki, T;Oyamada, M
• 通讯作者: Oyamada, M