Role of ATP7B in biliary copper excretion in a human hepatoma cell line and normal rat hepatocytes

被引:50
作者
Harada, M
Sakisaka, S
Terada, K
Kimura, R
Kawaguchi, T
Koga, H
Taniguchi, E
Sasatomi, K
Miura, N
Suganuma, T
Fujita, H
Furuta, K
Tanikawa, K
Sugiyama, T
Sata, M
机构
[1] Kurume Univ, Sch Med, Dept Med 2, Kurume, Fukuoka 8300011, Japan
[2] Akita Univ, Sch Med, Dept Biochem, Akita 010, Japan
[3] Miyazaki Med Coll, Dept Anat, Miyazaki 88916, Japan
[4] Kyushu Univ, Fac Pharmaceut Sci, Div Physiol Chem, Fukuoka 812, Japan
[5] Univ Occupat & Environm Hlth, Sch Hlth Sci, Dept Med Technol 1, Kitakyushu, Fukuoka, Japan
[6] Int Inst Liver Res, Kurume, Fukuoka, Japan
关键词
D O I
10.1016/S0016-5085(00)70178-8
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Background 65 Aims: Wilson's disease is a genetic disorder characterized by the accumulation of copper in the body caused by a defect of biliary copper excretion. The Wilson's disease gene has been cloned; however, the precise localization of the gene product (ATP7B) and its role in biliary copper excretion have not been clarified. Methods: We constructed a chimeric protein between green fluorescent protein (GFP) and ATP7B (GFP-ATP7B) and expressed it in a human hepatoma cell line (Huh7) and isolated rat hepatocytes. The Golgi apparatus, late endosomes, lysosomes, and bile canaliculus were visualized by fluorescence microscopy. Brefeldin A and nocodazole were used to redistribute the Golgi proteins. Bafilomycin A1 was used to analyze the association between GFP-ATP7B and the late endosomes. Results: GFP-ATP7B colocalized with rhodamine-dextran and late endosome markers but not with the Golgi markers, lysosome markers, or a tight junction protein. Brefeldin A and nocodazole redistributed the Golgi proteins, but they did not affect the distribution of ATP7B. Conclusions: Although it is widely believed that ATP7B is located at the Golgi apparatus, its main localization is in late endosomes. ATP7B seems to translocate copper from the cytosol to the late endosomal lumen, thus participating in biliary copper excretion via lysosomes.
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页码:921 / 928
页数:8
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