BACKGROUND & AIMS: Recently, we isolated a new complementary DNA (cDNA) encoding human liver-specific organic anion transporter (LST-1), representing the multispecificity of human liver. The aim of this study was to isolate a rat counterpart of human LST-1 and examine the expression regulation of its messenger RNA (mRNA) to clarify the molecular basis of cholestasis. METHODS: A rat liver cDNA library was screened with human LST-1 cDNA as a probe. Xenopus oocyte expression system was used for functional analysis. Northern blot analyses were performed using the isolated cDNA (termed rlst-1). The bile duct ligation model and the cecum ligation and puncture model were used for expression analyses. RESULTS: rlst-1 encodes 652 amino acids, predicting at least 11 transmembrane regions. The overall homology with human LST-1 was 60.2%, which is the highest among all known organic anion transporters. rlst-1 also belongs to the same new gene family as human LST-1, located between the organic anion transporter family and the prostaglandin transporter. rlst-1 preferably transports taurocholate (K(m), 9.45 micromol/L) in an Na(+)-independent manner. The rlst-1 mRNA is exclusively expressed in the liver. In both the bile duct ligation model and the cecum ligation and puncture model, mRNA expression levels of rlst-1 were down-regulated. CONCLUSIONS: rlst-1 is a counterpart of human LST-1 and is one of the important transporters in rat liver for the clearance of bile acid. The expression of rlst-1 may be under feedback regulation of cholestasis by biliary obstruction and/or sepsis.
BACKGROUND & AIMS: Recently, we isolated a new complementary DNA (cDNA) encoding human liver-specific organic anion transporter (LST-1), representing the multispecificity of human liver. The aim of this study was to isolate a rat counterpart of humanLST-1 and examine the expression regulation of its messenger RNA (mRNA) to clarify the molecular basis of cholestasis. METHODS: A rat liver cDNA library was screened with humanLST-1 cDNA as a probe. Xenopus oocyte expression system was used for functional analysis. Northern blot analyses were performed using the isolated cDNA (termed rlst-1). The bile duct ligation model and the cecum ligation and puncture model were used for expression analyses. RESULTS:rlst-1 encodes 652 amino acids, predicting at least 11 transmembrane regions. The overall homology with humanLST-1 was 60.2%, which is the highest among all known organic anion transporters. rlst-1 also belongs to the same new gene family as humanLST-1, located between the organic anion transporter family and the prostaglandin transporter. rlst-1 preferably transports taurocholate (K(m), 9.45 micromol/L) in an Na(+)-independent manner. The rlst-1 mRNA is exclusively expressed in the liver. In both the bile duct ligation model and the cecum ligation and puncture model, mRNA expression levels of rlst-1 were down-regulated. CONCLUSIONS:rlst-1 is a counterpart of humanLST-1 and is one of the important transporters in rat liver for the clearance of bile acid. The expression of rlst-1 may be under feedback regulation of cholestasis by biliary obstruction and/or sepsis.
Authors: Wen Zhao; Jeremiah D Zitzow; Yi Weaver; David J Ehresman; Shu-Ching Chang; John L Butenhoff; Bruno Hagenbuch Journal: Toxicol Sci Date: 2017-03-01 Impact factor: 4.849
Authors: Elke Gabriel; Stephanie Schievenbusch; Eugen Kolossov; Jan G Hengstler; Tamara Rotshteyn; Heribert Bohlen; Dirk Nierhoff; Jürgen Hescheler; Irina Drobinskaya Journal: PLoS One Date: 2012-09-24 Impact factor: 3.240