ArticleHepatology (Baltimore, Md.)2013
Taurolithocholate-induced MRP2 retrieval involves MARCKS phosphorylation by protein kinase Cϵ in HUH-NTCP Cells.
Article in Hepatology (Baltimore, Md.), 2013. 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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17 citing papers in PubMed, 30 citations in OpenAlex.
- Article
- Molecular Regulation of Canalicular ABC Transporters.International journal of molecular sciences · 2021Review
- Effect of P-glycoprotein (P-gp) Inducers on Exposure of P-gp Substrates: Review of Clinical Drug-Drug Interaction Studies.Clinical pharmacokinetics · 2020Review
- Farnesoid X Receptor Agonists Obeticholic Acid and Chenodeoxycholic Acid Increase Bile Acid Efflux in Sandwich-Cultured Human Hepatocytes: Functional Evidence and Mechanisms.The Journal of pharmacology and experimental therapeutics · 2018Article
- Misregulation of membrane trafficking processes in human nonalcoholic steatohepatitis.Journal of biochemical and molecular toxicology · 2018Article
- Mechanism of inhibition of taurolithocholate-induced retrieval of plasma membrane MRP2 by cyclic AMP and tauroursodeoxycholate.Physiological reports · 2017Article
- A Critical Evaluation of Liver Pathology in Humans with Danon Disease and Experimental Correlates in a Rat Model of LAMP-2 Deficiency.Clinical reviews in allergy & immunology · 2017Article
- Protein Kinases C-Mediated Regulations of Drug Transporter Activity, Localization and Expression.International journal of molecular sciences · 2017Review
- Nonalcoholic Steatohepatitis Modulates Membrane Protein Retrieval and Insertion Processes.Drug metabolism and disposition: the biological fate of chemicals · 2016Article
- p38 MAPK α and β isoforms differentially regulate plasma membrane localization of MRP2.American journal of physiology. Gastrointestinal and liver physiology · 2016Article
- Canalicular membrane MRP2/ABCC2 internalization is determined by Ezrin Thr567 phosphorylation in human obstructive cholestasis.Journal of hepatology · 2015Article
- Regulation of plasma membrane localization of the Na+-taurocholate cotransporting polypeptide (Ntcp) by hyperosmolarity and tauroursodeoxycholate.The Journal of biological chemistry · 2015Article
- Protein Kinase C-Independent Inhibition of Organic Cation Transporter 1 Activity by the Bisindolylmaleimide Ro 31-8220.PloS one · 2015Article
- Protein kinase Cδ protects against bile acid apoptosis by suppressing proapoptotic JNK and BIM pathways in human and rat hepatocytes.American journal of physiology. Gastrointestinal and liver physiology · 2014Article
- Role of protein kinase C isoforms in bile formation and cholestasis.Hepatology (Baltimore, Md.) · 2014Review
- Sodium-dependent bile salt transporters of the SLC10A transporter family: more than solute transporters.Pflugers Archiv : European journal of physiology · 2014Review
- INTRACELLULAR SIGNALING BY BILE ACIDS.Journal of bio-science · 2012Article
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3 authors at 1 institution in 1 country.
Funding
Abstract
unlabelledTaurolithocholate (TLC) acutely inhibits the biliary excretion of multidrug-resistant associated protein 2 (Mrp2) substrates by inducing Mrp2 retrieval from the canalicular membrane, whereas cyclic adenosine monophosphate (cAMP) increases plasma membrane (PM)-MRP2. The effect of TLC may be mediated via protein kinase Cϵ (PKCϵ). Myristoylated alanine-rich C kinase substrate (MARCKS) is a membrane-bound F-actin crosslinking protein and is phosphorylated by PKCs. MARCKS phosphorylation has been implicated in endocytosis, and the underlying mechanism appears to be the detachment of phosphorylated myristoylated alanine-rich C kinase substrate (pMARCKS) from the membrane. The aim of the present study was to test the hypothesis that TLC-induced MRP2 retrieval involves PKCϵ-mediated MARCKS phosphorylation. Studies were conducted in HuH7 cells stably transfected with sodium taurocholate cotransporting polypeptide (HuH-NTCP cells) and in rat hepatocytes. TLC increased PM-PKCϵ and decreased PM-MRP2 in both HuH-NTCP cells and hepatocytes. cAMP did not affect PM-PKCϵ and increased PM-MRP2 in these cells. In HuH-NTCP cells, dominant-negative (DN) PKCϵ reversed TLC-induced decreases in PM-MRP2 without affecting cAMP-induced increases in PM-MRP2. TLC, but not cAMP, increased MARCKS phosphorylation in HuH-NTCP cells and hepatocytes. TLC and phorbol myristate acetate increased cytosolic pMARCKS and decreased PM-MARCKS in HuH-NTCP cells. TLC failed to increase MARCKS phosphorylation in HuH-NTCP cells transfected with DN-PKCϵ, and this suggested PKCϵ-mediated phosphorylation of MARCKS by TLC. In HuH-NTCP cells transfected with phosphorylation-deficient MARCKS, TLC failed to increase MARCKS phosphorylation or decrease PM-MRP2.
conclusionTaken together, these results support the hypothesis that TLC-induced MRP2 retrieval involves TLC-mediated activation of PKCϵ followed by MARCKS phosphorylation and consequent detachment of MARCKS from the membrane.
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