ArticleThe Journal of biological chemistry2009
Activity of the bile salt export pump (ABCB11) is critically dependent on canalicular membrane cholesterol content.
Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
46 citing papers in PubMed, 113 citations in OpenAlex.
- Challenges in the diagnosis and treatment of genetic cholestasis in adults.JHEP reports : innovation in hepatology · 2026Review
- ATP8B1 regulates PIP2 localization and cleavage of pyroptotic executioner Gasdermin D.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Flipping the script: Advances in understanding how and why P4-ATPases flip lipid across membranes.Biochimica et biophysica acta. Molecular cell research · 2024Review
- Probing Liver Injuries Induced by Thioacetamide in Human In Vitro Pooled Hepatocyte Experiments.International journal of molecular sciences · 2024Article
- Intestinal Atp8b1 dysfunction causes hepatic choline deficiency and steatohepatitis.Nature communications · 2023Article
- Role and Regulation of Hepatobiliary ATP-Binding Cassette Transporters during Chemical-Induced Liver Injury.Drug metabolism and disposition: the biological fate of chemicals · 2022Review
- Article
- Two novel ATP8B1 mutations involved in progressive familial intrahepatic cholestasis type 1 that is ameliorated by rifampicin: A case report.Journal of digestive diseases · 2022Article
- Reduced spontaneous itch in mouse models of cholestasis.Scientific reports · 2021Article
- The phenotypic and transcriptomic effects of developmental exposure to nanomolar levels of estrone and bisphenol A in zebrafish.The Science of the total environment · 2021Article
- Molecular Regulation of Canalicular ABC Transporters.International journal of molecular sciences · 2021Review
- New paradigms of USP53 disease: normal GGT cholestasis, BRIC, cholangiopathy, and responsiveness to rifampicin.Journal of human genetics · 2021Article
- Current Models for Predicting Drug-induced Cholestasis: The Role of Hepatobiliary Transport System.Iranian journal of pharmaceutical research : IJPR · 2021Review
- Gene Therapy for Progressive Familial Intrahepatic Cholestasis: Current Progress and Future Prospects.International journal of molecular sciences · 2020Review
- Article
- Article
- Effect of food on the pharmacokinetics and therapeutic efficacy of 4-phenylbutyrate in progressive familial intrahepatic cholestasis.Scientific reports · 2019Article
- Assessment of ATP8B1 Deficiency in Pediatric Patients With Cholestasis Using Peripheral Blood Monocyte-Derived Macrophages.EBioMedicine · 2018Article
- Importance of detoxifying enzymes in differentiating fibrotic development between SHRSP5/Dmcr and SHRSP rats.Environmental health and preventive medicine · 2016Article
- ATP11C targets basolateral bile salt transporter proteins in mouse central hepatocytes.Hepatology (Baltimore, Md.) · 2016Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mutations in ATP8B1 cause severe inherited liver disease. The disease is characterized by impaired biliary bile salt excretion (cholestasis), but the mechanism whereby impaired ATP8B1 function results in cholestasis is poorly understood. ATP8B1 is a type 4 P-type ATPase and is a flippase for phosphatidylserine. Atp8b1-deficient mice display a dramatic increase in the biliary extraction of cholesterol from the canalicular (apical) membrane of the hepatocyte. Here we studied the hypothesis that disproportionate cholesterol extraction from the canalicular membrane impairs the activity of the bile salt transporter, ABCB11, and as a consequence causes cholestasis. Using single pass liver perfusions, we show that not only ABCB11-mediated transport but also Abcc2-mediated transport were reduced at least 4-fold in Atp8b1 deficiency. We show that canalicular membranes of cholestatic Atp8b1-deficient mice have a dramatically reduced cholesterol to phospholipid ratio, i.e. 0.75 +/- 0.24 versus 2.03 +/- 0.71 for wild type. In vitro depletion of cholesterol from mouse liver plasma membranes using methyl-beta-cyclodextrin demonstrated a near linear relation between cholesterol content of the membranes and ATP-dependent taurocholate transport. Abcc2-mediated transport activity was not affected up to 30% of membrane cholesterol depletion but declined to negligible levels at 70% of membrane cholesterol depletion. These effects were reversible as cholesterol repletion of the liver membranes completely restored Abcb11- and Abcc2-mediated transport. Our data demonstrate that membrane cholesterol content is a critical determinant of ABCB11/ABCC2 transport activity, provide an explanation for the etiology of ATP8B1 disease, and suggest a novel mechanism protecting the canalicular membrane against luminal bile salt overload.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.