Multidrug resistance associated protein 1 protects against bilirubin-induced cytotoxicity

被引：30

作者：

Calligaris, S

Cekic, D

Roca-Burgos, L

Gerin, F

Mazzone, G

Ostrow, JD

Tiribelli, C

机构：

[1] Ctr Studi Fegato, I-34012 Trieste, Italy

[2] Univ Trieste, Dept BBCM, I-34012 Trieste, Italy

[3] Univ Washington, GI Hepatol Div, Seattle, WA 98195 USA

来源：

FEBS LETTERS | 2006年 / 580卷 / 05期

关键词：

D O I：

10.1016/j.febslet.2006.01.056

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

We have shown that multidrug resistance associated protein 1 (MRP1) mediates ATP-dependent extrusion of bilirubin, possibly limiting its potentially toxic accumulation in cells. To determine directly if Mrp1 protects cells against unconjugated bilirubin (UCB) toxicity, mouse embryo fibroblasts (MEF) were isolated from Mrp1 knockout (-/-) mice and their wild type (WT) (+/+) littermates. Compared to WT cells, cultured MEF (-/-) cells exposed to 40-140 nM unbound [H-3]-bilirubin accumulated twice as much [H-3]-bilirubin (P < 0.01). This was associated with greater, dose-related cytotoxicity, assessed by the methylthiazoletetrazolium test, lactate dehydrogenase release and cellular ATP content. The data confirm that Mrp1 limits intracellular accumulation of UCB and thus decreases its cytotoxicity. (c) 2006 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

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收藏

页码：1355 / 1359

页数：5

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