2010 Fiscal Year Final Research Report
New drug therapy of the transporter-related diseases through the modulation of membrane trafficking
| Project/Area Number |
21790146
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Medical pharmacy
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| Research Institution | The University of Tokyo |
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Principal Investigator |
HAYASHI Hisamitsu The University of Tokyo, 大学院・薬学系研究科, 助教 (10451858)
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| Project Period (FY) |
2009 – 2010
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| Keywords | トランスポーター / 肝内胆汁うっ滞 / 細胞内ソーティング / 胆汁酸 / フェニルブチレート / コレステロール |
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| Research Abstract |
Bile salt export pump (BSEP) localizes on canalicular membrane of hepatocytes and mediates biliary excretion of bile salts. BSEP dysfunction attributed to its internalization from hepatocanalicular membrane and subsequent degradation causes intrahepatic cholestasis. At present, no medical therapy for this disease state has been established, because the regulatory mechanism of cell surface expression of BSEP remains to be elucidated. In this study, we explored it focusing on posttranslational machinery and demonstrated that ubiquitination, a posttranslational modification, is an internalization signal of BSEP and that AP2, an adaptor protein for clathrin-mediated endocytosis, is associated with BSEP internazliation through its direct interaction with BSEP.
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[Journal Article] Favorable effect of 4-phenylacetate on liver functions attributable to enhanced bile salt export pump expression in ornithine transcarbamylase-deficient children.2010
Author(s)
Nagasaka H, Yorifuji T, Kobayashi K, Takikawa H, Komatsu H, Inui A, Fujisawa T, Miida T, Tsukahara H, Takatani T, Hayashi H.
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Journal Title
Mol Genet Metab. 100(2)
Pages: 123-128
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[Remarks] ホームページ等
