Adenosine triphosphate-dependent copper transport in human liver

被引:14
作者
Dijkstra, M
vandenBerg, GJ
Wolters, H
Veld, GI
Slooff, MJH
Heymans, GSA
Kuipers, F
Vonk, RJ
机构
[1] UNIV GRONINGEN HOSP, GRONINGEN INST DRUG STUDIES, DEPT PEDIAT, GRONINGEN, NETHERLANDS
[2] UNIV GRONINGEN HOSP, GRONINGEN INST DRUG STUDIES, DEPT SURG, GRONINGEN, NETHERLANDS
[3] DELFT UNIV TECHNOL, INST INTERFAC REACTOR, NL-2629 JB DELFT, NETHERLANDS
关键词
bile canalicular membrane; copper; P-type ATPase; transport kinetics; vesicle; Wilson disease;
D O I
10.1016/S0168-8278(96)80325-4
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Background/Aim: The recent cloning and sequencing of the Wilson disease gene indicates that hepatic copper (Cu) transport is mediated by a P-type ATPase. The location of this Cu-transporting protein within the hepatocyte is not known; in view of its proposed function and current concepts of hepatic Cu transport, it may reside in intracellular membranes (endoplasmic reticulum (ER), lysosomes) and/or in the bile canalicular membrane, The objective of this study was to establish characteristics and localization of ATP-dependent Cu transport in human liver. Methods: We have investigated Cu transport in vesicles of human liver plasma membranes showing a gradual increase in enrichment of canalicular domain markers: i.e. basolateral liver plasma membranes (blLPM), a mixed population of basolateral and canalicular (XLPM) and canalicular liver plasma membranes (cLPM). Results: In the presence of ATP (4 mM) and an ATP-regenerating system, uptake of radiolabeled Cu (Cu-64, 10 mu M) into cLPM vesicles and, to a lesser extent, into blLPM and XLPM was clearly stimulated when compared to control AMP values. Initial uptake rates of ATP-dependent Cu transport were 5.6, 7.8 and 13.7 nmol . min(-1). mg(-1) protein for blLPM, XLPM and cLPM, respectively, and showed no relationship with marker enzyme activity of ER and lysosomes (glucose-6-phosphatase and acid-phosphatase, respectively). Leucine aminopeptidase activity, as a marker for the cLPM, significantly correlated with ATP-dependent uptake rates measured in different membrane preparations: r=0.70 (n=9, p<0.05). Estimated K-m and V-max values of ATP-dependent Cu uptake were 49.5 mu M and 36.9 nmol . min(-1). mg(-1) protein, respectively. Conclusion: This study provides biochemical evidence for the presence of an ATP-dependent Cu transport system in human liver (cCOP), mainly localized at the canalicular domain of the hepatocytic plasma membrane.
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页码:37 / 42
页数:6
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