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J Biochem Mol Toxicol. 2018 Mar;32(3):e22035. doi: 10.1002/jbt.22035. Epub 2018 Jan 17.

Misregulation of membrane trafficking processes in human nonalcoholic steatohepatitis.

Author information

1
Department of Pharmacology & Toxicology, University of Arizona, Tucson, AZ, USA.

Abstract

Nonalcoholic steatohepatitis (NASH) remodels the expression and function of genes and proteins that are critical for drug disposition. This study sought to determine whether disruption of membrane protein trafficking pathways in human NASH contributes to altered localization of multidrug resistance-associated protein 2 (MRP2). A comprehensive immunoblot analysis assessed the phosphorylation, membrane translocation, and expression of transporter membrane insertion regulators, including several protein kinases (PK), radixin, MARCKS, and Rab11. Radixin exhibited a decreased phosphorylation and total expression, whereas Rab11 had an increased membrane localization. PKCδ, PKCα, and PKA had increased membrane activation, whereas PKCε had a decreased phosphorylation and membrane expression. Radixin dephosphorylation may activate MRP2 membrane retrieval in NASH; however, the activation of Rab11/PKCδ and PKA/PKCα suggest an activation of membrane insertion pathways as well. Overall these data suggest an altered regulation of protein trafficking in human NASH, although other processes may be involved in the regulation of MRP2 localization.

KEYWORDS:

MRP2; NASH; biliary elimination

PMID:
29341352
PMCID:
PMC5854531
DOI:
10.1002/jbt.22035
[Indexed for MEDLINE]
Free PMC Article

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