title: Enhancement of interaction of BSEP and HAX-1 on the canalicular membrane of hepatocytes in a mouse model of cholesterol cholelithiasis.
abstract: We induced gallstones in C57L mice fed with a high cholesterol diet and examined the expression of bile salt export pump (BSEP) on the canalicular membrane of hepatocytes and its relation with PKCα and HAX-1.Twenty-four gallstone-prone C57L mice were randomly assigned to receive a high cholesterol diet or a regular diet. Gallstone formation was recorded. BSEP, PKCα and phospho-PKCα expression was examined by immunoblotting assays. Co-expression of BSEP and HAX-1 was studied by immunofluorescent microscopy and immunoprecipitations. Gallstones were formed in all 12 mice fed with the high cholesterol diet. In Gallstone group, BSEP levels on the canalicular membrane of hepatocytes were markedly lower while a significant increase was observed in phosphorylated PKCα. Immunofluorescent microscopy showed that BSEP and HAX-1 were co-localized on the canalicular membrane, which was apparently enhanced by feeding with the high cholesterol diet. The immunoprecipitation assays further demonstrated that BSEP and HAX-1 showed enhanced interaction in the hepatocytes of mice fed with the high cholesterol diet. Cholesterol gallstone formation is associated with downregulation of BSEP expression on the canalicular membrane of hepatocytes with increased phosphorylation of PKCα. BSEP and HAX-1 show enhanced interaction with one another on the canalicular membrane during gallstone formation.
authors.affiliation: Department of Biliary and Minimally Invasive Surgery, China Medical University Shengjing Hospital Shenyang, Liaoning, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Kong
authors.affiliation: Department of Biliary and Minimally Invasive Surgery, China Medical University Shengjing Hospital Shenyang, Liaoning, China.
authors.forename: Bin-Bin
authors.initials: BB
authors.lastname: Liu
authors.affiliation: Department of Biliary and Minimally Invasive Surgery, China Medical University Shengjing Hospital Shenyang, Liaoning, China.
authors.forename: Shuo-Dong
authors.initials: SD
authors.lastname: Wu
authors.affiliation: Department of Biliary and Minimally Invasive Surgery, China Medical University Shengjing Hospital Shenyang, Liaoning, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Biliary and Minimally Invasive Surgery, China Medical University Shengjing Hospital Shenyang, Liaoning, China.
authors.forename: Qing-Quan
authors.initials: QQ
authors.lastname: Jiang
authors.affiliation: Department of Biliary and Minimally Invasive Surgery, China Medical University Shengjing Hospital Shenyang, Liaoning, China.
authors.forename: En-Ling
authors.initials: EL
authors.lastname: Guo
mesh_terms: D000074020:ATP Binding Cassette Transporter, Subfamily B, Member 11; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism*; D000818:Animals; D001646:Bile / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism*; D002769:Cholelithiasis / Q000139:chemically induced* / Q000378:metabolism* / Q000473:pathology; D002791:Cholesterol, Dietary / Q000009:adverse effects* / Q000378:metabolism; D004195:Disease Models, Animal; D015536:Down-Regulation; D022781:Hepatocytes / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010766:Phosphorylation; D051571:Protein Kinase C-alpha / Q000378:metabolism; D011506:Proteins / Q000378:metabolism*; D014280:Triglycerides / Q000378:metabolism
chemical_list: D000074020:ATP Binding Cassette Transporter, Subfamily B, Member 11; D018528:ATP-Binding Cassette Transporters; C490549:Abcb11 protein, mouse; D002791:Cholesterol, Dietary; C491295:Hs1bp1 protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; D011506:Proteins; D014280:Triglycerides; D051571:Protein Kinase C-alpha
keywords: BSEP; Gallstone; HAX-1; canaliculi; cholesterol