The ATP-binding cassette (ABC) transporters expressed at the canalicular membrane of hepatocytes mediate the secretion of several compounds into the bile canaliculi and therefore play a key role in bile secretion. Among these transporters, ABCB11 secretes bile acids, ABCB4 translocates phosphatidylcholine and ABCG5/G8 is responsible for cholesterol secretion, while ABCB1 and ABCC2 transport a variety of drugs and other compounds. The dysfunction of these transporters leads to severe, rare, evolutionary biliary diseases. The development of new therapies for patients with these diseases requires a deep understanding of the biology of these transporters. In this review, we report the current knowledge regarding the regulation of canalicular ABC transporters' folding, trafficking, membrane stability and function, and we highlight the role of molecular partners in these regulating mechanisms.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7924332 | PMC |
| http://dx.doi.org/10.3390/ijms22042113 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
A Study of Short-Chain Fatty Acids During the Canalicular and Early Saccular Phases of Fetal Lung Development and Childhood Asthma.
Genes (Basel)
December 2024
Biostatistics and Computational Biology Branch (BCBB), National Institute of Environmental Health Sciences (NIEHS), NIH, Durham, NC 27709, USA.
Background: Emerging literature indicates that the microbiome and its byproducts, such as short-chain fatty acids (SCFAs), play an important role in childhood diseases such as allergies and asthma. Specifically, there is evidence suggesting that SCFAs play a critical role in fetal immunoprogramming during the late saccular phase of fetal lung development. An increase in acetate during the late saccular phase is known to play a critical role in inhibiting histone deacetylases (HDACs), resulting in a cascade of events, including Treg immune regulation, involved in fetal immunoprogramming, and reduction in the asthma phenotype.
View Article and Find Full Text PDFEffects of mixed exposure to PFAS on adolescent non-alcoholic fatty liver disease: Integrating evidence from human cohorts, toxicogenomics, and animal models to uncover mechanisms and potential target sites.
J Hazard Mater
December 2024
Key Laboratory of the Public Health Safety, Ministry of Education, Department of Environmental Health, School of Public Health, Fudan University, Shanghai 200032, China; Key Laboratory of Health Technology Assessment, National Health Commission of the People's Republic of China, Fudan University, Shanghai 200032, China; Center for Water and Health, School of Public Health, Fudan University, Shanghai 200032, China. Electronic address:
Extensive evidence suggests a correlation between environmental pollutants, specifically perfluoroalkyl and polyfluoroalkyl substances (PFAS) and non-alcoholic fatty liver disease (NAFLD). This study aims to investigate the association and underlying mechanisms of PFAS-induced NAFLD in adolescents by employing a comprehensive approach of population-based studies, toxicogenomics, and animal models. A total of 2014 freshmen from Dali University were recruited for this study, with 1694 participants undergoing serum testing for PFAS exposure.
View Article and Find Full Text PDFAltered post-fracture systemic bone loss in a mouse model of osteocyte dysfunction.
JBMR Plus
December 2024
Department of Orthopaedic Surgery, University of California Davis Medical Center, Sacramento, CA 95817, United States.
Femur fracture leads to loss of bone at uninjured skeletal sites, which may increase risk of subsequent fracture. Osteocytes, the most abundant bone cells, can directly resorb bone matrix and regulate osteoclast and osteoblast activity, but their role in systemic bone loss after fracture remains poorly understood. In this study we used a transgenic (TG+) mouse model that overexpresses human B-cell lymphoma 2 (BCL-2) in osteoblasts and osteocytes.
View Article and Find Full Text PDFDrug-induced cholestasis (DIC) predictions based on in vitro inhibition of major bile acid clearance mechanisms.
Arch Toxicol
January 2025
Pharmacokinetic Sciences, BioMedical Research, Novartis, Basel, Switzerland.
Article Synopsis
- Drug-induced cholestasis (DIC) is a significant concern in drug development, as it disrupts bile flow and causes toxic buildup of bile acids in the liver, representing a type of drug-induced liver injury (DILI).
- Researchers developed a predictive model using in vitro data from 47 drugs, which distinguished between drugs with and without DILI concerns, achieving a strong predictive performance (p-value of 0.039, PR AUC of 0.91).
- The study highlights the importance of multiple liver processes in bile acid regulation and suggests that using a quantitative model in preclinical stages can improve drug safety and reduce failures in later development stages.
Induction of drug metabolizing enzyme and drug transporter expression by antifungal triazole pesticides in human HepaSH hepatocytes.
Chemosphere
October 2024
Univ Rennes, CHU Rennes, Inserm, EHESP, Irset (Institut de recherche en santé, environnement et travail) - UMR_S 1085, F-35000, Rennes, France. Electronic address:
Triazole pesticides are widely used fungicides, to which humans are rather highly exposed. They are known to activate drug-sensing receptors regulating expression of hepatic drug metabolizing enzymes and drug transporters, thus suggesting that the hepatic drug detoxification system is modified by these agrochemicals. To investigate this hypothesis, the effects of 9 triazole fungicides towards expression of drug metabolizing enzymes and transporters were characterized in cultured human HepaSH cells, that are human hepatocytes deriving from chimeric humanized liver TK-NOG mice.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!