Improved hepatic MRP2/ABCC2 transport activity in LPS-induced cholestasis by aquaporin-1 gene transfer

被引:9
作者
Marrone, Julieta [1 ]
Tocchetti, Guillermo N. [1 ]
Danielli, Mauro [1 ]
Mottino, Aldo D. [1 ]
Marinelli, Raul A. [1 ]
机构
[1] Univ Nacl Rosario, Inst Fisiol Expt, CONICET, Fac Ciencias Bioquim & Farmaceut, RA-2000 Rosario, Santa Fe, Argentina
关键词
Aquaporin-1; Cholestasis triggered by LPS; Biliary glutathione excretion; Multidrug resistance-associated protein-2; Adenoviral gene transfer; LIVER; MRP2; LIPOPOLYSACCHARIDE; LOCALIZATION; GLUTATHIONE; EXPRESSION; PROTEIN-2; EXCRETION; RATS;
D O I
10.1016/j.biochi.2019.07.027
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
Multidrug resistance-associated protein 2 (MRP2/ABCC2), a hepatocyte canalicular transporter involved in bile secretion, is downregulated in cholestasis triggered by lipopolysaccharide. The human aquaporin-1 (hAQP1) adenovirus-mediated gene transfer to liver improves cholestasis by incompletely defined mechanisms. Here we found that hAQP1 did not affect MRP2/ABCC2 expression, but significantly increased its transport activity assessed in situ with endogenous and exogenous substrates, likely by a hAQP1-induced increase in canalicular membrane cholesterol amount. Our results suggest that hAQP1-induced MRP2/ABCC2 activation contributes to the cholestasis improvement. (C) 2019 Elsevier B.V. and Societe Francaise de Biochimie et Biologie Moleculaire (SFBBM). All rights reserved.
引用
收藏
页码:179 / 182
页数:4
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