ArticlePloS one2016
Functional Rescue of Trafficking-Impaired ABCB4 Mutants by Chemical Chaperones.
Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed.
- Curcumin-based compounds in non-malignant biliary injury and cholangiocarcinoma: mechanistic insights and translational barriers.Frontiers in pharmacology · 2026Review
- A structural and mechanistic model for BSEP dysfunction in PFIC2 cholestatic disease.Communications biology · 2025Article
- Metabolomics Combined with Physiology and Transcriptomics Reveal the Response ofAntioxidants (Basel, Switzerland) · 2024Article
- Influence of the Bile Acid Transporter GenesJournal of personalized medicine · 2023Article
- Medically Important Alterations in Transport Function and Trafficking of ABCG2.International journal of molecular sciences · 2021Review
- Identification of Specific Trafficking Defects of Naturally Occurring Variants of the Human ABCG2 Transporter.Frontiers in cell and developmental biology · 2021Article
- Molecular overview of progressive familial intrahepatic cholestasis.World journal of gastroenterology · 2020Review
- Case report: progressive familial intrahepatic cholestasis type 3 with compound heterozygous ABCB4 variants diagnosed 15 years after liver transplantation.BMC medical genetics · 2020Article
- Pediatric Cholestasis: Epidemiology, Genetics, Diagnosis, and Current Management.Clinical liver disease · 2020Review
- Cellular Processing of the ABCG2 Transporter-Potential Effects on Gout and Drug Metabolism.Cells · 2019Review
- Chaperoning Endoplasmic Reticulum-Associated Degradation (ERAD) and Protein Conformational Diseases.Cold Spring Harbor perspectives in biology · 2019Review
- Expanding etiology of progressive familial intrahepatic cholestasis.World journal of hepatology · 2019Article
- Structural analogues of roscovitine rescue the intracellular traffic and the function of ER-retained ABCB4 variants in cell models.Scientific reports · 2019Article
- Familial Hypercholesterolemia: The Most Frequent Cholesterol Metabolism Disorder Caused Disease.International journal of molecular sciences · 2018Review
- Phenotypic spectrum and diagnostic pitfalls of ABCB4 deficiency depending on age of onset.Hepatology communications · 2018Article
- Molecular mechanisms underlying the pilsicainide-induced stabilization of hERG proteins in transfected mammalian cells.Journal of arrhythmia · 2017Article
- Current and future therapies for inherited cholestatic liver diseases.World journal of gastroenterology · 2017Review
Corrections and comments
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Authors and funding
5 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Multidrug resistance protein 3 (MDR3, ABCB4) is a hepatocellular membrane protein that mediates biliary secretion of phosphatidylcholine. Null mutations in ABCB4 gene give rise to severe early-onset cholestatic liver disease. We have previously shown that the disease-associated mutations p.G68R, p.G228R, p.D459H, and p.A934T resulted in retention of ABCB4 in the endoplasmic reticulum, thus failing to target the plasma membrane. In the present study, we tested the ability of two compounds with chaperone-like activity, 4-phenylbutyrate and curcumin, to rescue these ABCB4 mutants by assessing their effects on subcellular localization, protein maturation, and phospholipid efflux capability. Incubation of transfected cells at a reduced temperature (30°C) or exposure to pharmacological doses of either 4-PBA or curcumin restored cell surface expression of mutants G228R and A934T. The delivery of these mutants to the plasma membrane was accompanied by a switch in the ratio of mature to inmature protein forms, leading to a predominant expression of the mature protein. This effect was due to an improvement in the maturation rate and not to the stabilization of the mature forms. Both mutants were also functionally rescued, displaying bile salt-dependent phospholipid efflux activity after addition of 4-PBA or curcumin. Drug-induced rescue was mutant specific, given neither 4-PBA nor curcumin had an effect on the ABCB4 mutants G68R and A934T. Collectively, these data indicate that the functionality of selected trafficking-defective ABCB4 mutants can be recovered by chemical chaperones through restoration of membrane localization, suggesting a potential treatment for patients carrying such mutations.
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