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

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 defi...

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Bibliographic Details
Published in:Biochimie 2019-10, Vol.165, p.179-182
Main Authors: Marrone, Julieta, Tocchetti, Guillermo N., Danielli, Mauro, Mottino, Aldo D., Marinelli, Raúl A.
Format: Article
Language:English
Subjects:
Adenoviral gene transfer
Animals
Aquaporin 1 - genetics
Aquaporin 1 - physiology
Aquaporin-1
ATP-Binding Cassette Transporters - metabolism
Bile - metabolism
Biliary glutathione excretion
Cholestasis - metabolism
Cholestasis - therapy
Cholestasis triggered by LPS
Gene Transfer Techniques
Hepatocytes - cytology
Hepatocytes - metabolism
Male
Multidrug resistance-associated protein-2
Rats, Wistar
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Summary: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. •Hepatic gene transfer of human aquaporin-1 (hAQP1) improves LPS-induced cholestasis.•hAQP1 increases liver MRP2/ABCC2 transport activity without affecting its expression.•MRP2/ABCC2 activation would be due to hAQP1-increased canalicular cholesterol content.•hAQP1-induced MRP2/ABCC2 activation contributes to improve LPS cholestasis.
ISSN:0300-9084
1638-6183
DOI:10.1016/j.biochi.2019.07.027