Analysis of functional significance of a newly discovered brain-specific transporter

新发现的脑特异性转运蛋白的功能意义分析

• 批准号: 20390044
• 负责人: NAKAJIMA Akira
• 金额: $ 12.56万
• 依托单位: Nagoya University (2009-2010)Tohoku University (2008)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2008
• 资助国家: 日本
• 起止时间: 2008 至 2010
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-20390044/
• 关键词: トランスポーター; 胆汁酸; 黒質; in silico; 黒室

We have focused on a newly discovered human brain-specific transporter SLC10A4, which is specifically localized in the substantia nigra. Over-expression cell of human SLC10A4 was successfully generated using human HepG2 cell. A low SLC10A4-mediated uptake of bile acids, such as chenodeoxycholic acid and ursodeoxycholic acid, was observed in the transformant. The expression of SLC10A4 was investigated in various cultured cells using immunoblot analysis. Finally, human brain-derived TE671(medulloblastoma) cells were found that they had a stable expression of SLC10A4. It was noteworthy finding that the uptake of taurocholic acid was induced by thrombin pretreatment in the TE671 cells and the Km value was higher than that of known sodium taurocholate co-transporting polypeptides, such as ASBT and NTCP. We considered that SLC10A4 was special brain transporter, could be activated and responsible for the uptake of bile acids when blood clotting was occurred following blood vessel damage or tissue injury.

我们专注于新发现的人脑特异性转运蛋白SLC10A4，它特异性地定位于黑质。利用人HepG2细胞成功构建了人SLC10A4的过表达细胞。在小肠中观察到SLC10A4介导的胆汁酸（如鹅去氧胆酸和熊去氧胆酸）摄取较低。使用免疫印迹分析在各种培养的细胞中研究SLC10A4的表达。最后，发现人脑源性TE 671（髓母细胞瘤）细胞稳定表达SLC 10A4。值得注意的是，在TE 671细胞中，凝血酶预处理诱导牛磺胆酸的摄取，并且Km值高于已知的牛磺胆酸钠共转运多肽，如ASBT和NTCP。我们认为，SLC10A4是一种特殊的脑转运蛋白，在血管损伤或组织损伤后发生凝血时，可被激活并参与胆汁酸的摄取。

项目成果

Simple quantification of lansoprazole and rabeprazole concentrations in human serum by liquid chromatography/tandem mass spectrometry

• DOI: 10.1016/j.jchromb.2008.05.034
• 发表时间: 2008-07-01
• 期刊: JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES
• 影响因子: 3
• 作者: Hishinuma, Takanori;Suzuki, Kaori;Goto, Junichi
• 通讯作者: Goto, Junichi

LC/MS/MSを用いたOATP1B3の絶対定量と過剰発現細胞のプロテオーム解析

使用 LC/MS/MS 对 OATP1B3 进行绝对定量和过表达细胞的蛋白质组分析

• 发表时间: 2011
• 作者: Ayumi Yamada;Ose A他;阿部拓哉ら;金光祥臣ら
• 通讯作者: 金光祥臣ら

The Nutrient Formula Containing Eicosapentaenoic Acid and Docosahexaenoic Acid Benefits the Fatty Acid Status of Patients Receiving Long-Term Enteral Nutrition

• DOI: 10.1620/tjem.217.23
• 发表时间: 2009-01-01
• 期刊: TOHOKU JOURNAL OF EXPERIMENTAL MEDICINE
• 影响因子: 2.2
• 作者: Munakata, Mitsutoshi;Nishikawa, Masazumi;Onuma, Akira
• 通讯作者: Onuma, Akira

胆汁酸トランスポーターSLC10A4の機能解析

胆汁酸转运蛋白SLC10A4的功能分析

• 发表时间: 2012
• 作者: 阿部拓哉;ら
• 通讯作者: ら

ヒト小脳由来TE671細胞におけるプロテアーゼ活性化トランスポーターの機能解析

人小脑来源的 TE671 细胞中蛋白酶激活转运蛋白的功能分析

• 发表时间: 2011
• 作者: Ayumi Yamada;Ose A他;阿部拓哉ら
• 通讯作者: 阿部拓哉ら