BACKGROUND & AIMS: Protein is secreted into bile via several independent pathways. The aim of this study was to investigate whether these pathways are influenced by secretion of biliary lipid. METHODS: Protein secretion and biliary lipid output were studied in wild-type mice (+/+), heterozygotes (+/-), and homozygotes (-/-) for mdr2 gene disruption. Biliary lipid and protein output were varied by infusion with taurocholate (TC) and tauroursodeoxycholate (TUDC). RESULTS: Exocytosis and transcytosis were unaltered in (-/-) mice. Infusion with TC strongly induced secretion of alkaline phosphatase in (-/-) mice but had little effect in (+/-) and (+/+) mice. Infusion with TUDC had little effect on alkaline phosphatase output. In contrast, both TUDC and TC strongly stimulated secretion of aminopeptidase N and lysosomal enzymes in (+/+) mice but had no effect in (-/-) animals. Aminopeptidase N secretion correlated with phospholipid output, but only at high flux. At low flux, aminopeptidase N was secreted independently from both phospholipid and bile salts. CONCLUSIONS: The canalicular membrane enzymes alkaline phosphatase and aminopeptidase N are secreted via separate pathways. Part of alkaline phosphatase output is controlled by bile salt hydrophobicity, whereas at high lipid flux, aminopeptidase N secretion seems to be coupled to phospholipid output. Lysosomal enzymes follow the latter pathway.
BACKGROUND & AIMS: Protein is secreted into bile via several independent pathways. The aim of this study was to investigate whether these pathways are influenced by secretion of biliary lipid. METHODS: Protein secretion and biliary lipid output were studied in wild-type mice (+/+), heterozygotes (+/-), and homozygotes (-/-) for mdr2 gene disruption. Biliary lipid and protein output were varied by infusion with taurocholate (TC) and tauroursodeoxycholate (TUDC). RESULTS: Exocytosis and transcytosis were unaltered in (-/-) mice. Infusion with TC strongly induced secretion of alkaline phosphatase in (-/-) mice but had little effect in (+/-) and (+/+) mice. Infusion with TUDC had little effect on alkaline phosphatase output. In contrast, both TUDC and TC strongly stimulated secretion of aminopeptidase N and lysosomal enzymes in (+/+) mice but had no effect in (-/-) animals. Aminopeptidase N secretion correlated with phospholipid output, but only at high flux. At low flux, aminopeptidase N was secreted independently from both phospholipid and bile salts. CONCLUSIONS: The canalicular membrane enzymes alkaline phosphatase and aminopeptidase N are secreted via separate pathways. Part of alkaline phosphatase output is controlled by bile salt hydrophobicity, whereas at high lipid flux, aminopeptidase N secretion seems to be coupled to phospholipid output. Lysosomal enzymes follow the latter pathway.
Authors: Qiaoli Li; Joshua Kingman; Koen van de Wetering; Sami Tannouri; John P Sundberg; Jouni Uitto Journal: J Invest Dermatol Date: 2017-01-19 Impact factor: 8.551
Authors: Sohela Shah; Ukina R Sanford; Julie C Vargas; Hongmei Xu; Annamiek Groen; Coen C Paulusma; James P Grenert; Ludmila Pawlikowska; Saunak Sen; Ronald P J Oude Elferink; Laura N Bull Journal: PLoS One Date: 2010-02-01 Impact factor: 3.240
Authors: Lisa Reinhard; Christian Rupp; Hans-Dieter Riedel; Thomas Ruppert; Thomas Giese; Christa Flechtenmacher; Karl Heinz Weiss; Petra Kloeters-Plachky; Wolfgang Stremmel; Peter Schirmacher; Peter Sauer; Daniel Nils Gotthardt Journal: PLoS One Date: 2012-01-11 Impact factor: 3.240