PMID- 33582321
OWN - NLM
STAT- MEDLINE
DCOM- 20220201
LR  - 20220201
IS  - 1665-2681 (Print)
IS  - 1665-2681 (Linking)
VI  - 24
DP  - 2021 Sep-Oct
TI  - Effect of bile acids on the expression of MRP3 and MRP4: An In vitro study in 
      HepG2 cell line.
PG  - 100325
LID - S1665-2681(21)00024-7 [pii]
LID - 10.1016/j.aohep.2021.100325 [doi]
AB  - INTRODUCTION AND OBJECTIVES: Free and conjugated bile acids (BA's) cannot cross 
      cell membranes; therefore, a particular transport system is required by the cell. 
      Members of the family of ABC (ATP-binding proteins) transporters transfer bile 
      acids in and out of the cell, preventing their accumulation. High intracellular 
      concentrations of bile acids, such as those observed in cholestasis, have been 
      related to oxidative stress and apoptosis, which in many cases are the leading 
      causes of hepatocyte damage. MRP3 and MRP4 (multidrug resistance-associated 
      protein 3 and 4) proteins belong to the ABC subfamily C, and are transporters of 
      the hepatocyte's basolateral membrane with a compensatory role. Both 
      transporters' increased expression constitutes an essential role in the 
      protective and adaptive responses of bile acid overload, such as cholestasis. 
      This work aimed to analyze both transporters' mRNA and protein expression in an 
      in vitro model of cholestasis using HepG2 cell line treated with main bile acids. 
      METHODS: The expression of transporters was investigated through confocal 
      microscopy immunofluorescence, Western Blot, and RT-qPCR after the main bile 
      acids in HepG2 line cells. RESULTS: The results showed the relation between 
      confluence and expression of both transporters in the plasma membrane. MRP3 
      showed atypical and heterogeneous distribution in this cell line. CDCA 
      (chenodeoxycholic acid) at low concentrations induced the expression of mRNA of 
      both transporters. In contrast, protein expression was induced by CA (cholic 
      acid) at high concentrations. CONCLUSION: Primary bile acids (CDCA and CA) induce 
      overexpression of the MRP4 and MRP3 transporters in the HepG2 cell line.
CI  - Copyright (c) 2021 Fundacion Clinica Medica Sur, A.C. Published by Elsevier Espana, 
      S.L.U. All rights reserved.
FAU - Perez-Pineda, Suilma Ivette
AU  - Perez-Pineda SI
AD  - Departamento de Infectomica y Patogenesis Molecular, Centro de Investigacion y de 
      Estudios Avanzados del Instituto Politecnico Nacional, Mexico City, Mexico. 
      Electronic address: siperez@cinvestav.mx.
FAU - Baylon-Pacheco, Lidia
AU  - Baylon-Pacheco L
AD  - Departamento de Infectomica y Patogenesis Molecular, Centro de Investigacion y de 
      Estudios Avanzados del Instituto Politecnico Nacional, Mexico City, Mexico. 
      Electronic address: lbaylon@cinvestav.mx.
FAU - Espiritu-Gordillo, Patricia
AU  - Espiritu-Gordillo P
AD  - Departamento de Infectomica y Patogenesis Molecular, Centro de Investigacion y de 
      Estudios Avanzados del Instituto Politecnico Nacional, Mexico City, Mexico. 
      Electronic address: pespiritu@cinvestav.mx.
FAU - Tsutsumi, Victor
AU  - Tsutsumi V
AD  - Departamento de Infectomica y Patogenesis Molecular, Centro de Investigacion y de 
      Estudios Avanzados del Instituto Politecnico Nacional, Mexico City, Mexico. 
      Electronic address: vtsutsu@cinvestav.mx.
FAU - Rosales-Encina, Jose Luis
AU  - Rosales-Encina JL
AD  - Departamento de Infectomica y Patogenesis Molecular, Centro de Investigacion y de 
      Estudios Avanzados del Instituto Politecnico Nacional, Mexico City, Mexico. 
      Electronic address: rosales@cinvestav.mx.
LA  - eng
PT  - Journal Article
DEP - 20210211
PL  - Mexico
TA  - Ann Hepatol
JT  - Annals of hepatology
JID - 101155885
RN  - 0 (ABCC4 protein, human)
RN  - 0 (Bile Acids and Salts)
RN  - 0 (Gastrointestinal Agents)
RN  - 0 (Multidrug Resistance-Associated Proteins)
RN  - 0 (RNA, Messenger)
RN  - 1YV0492L5Z (multidrug resistance-associated protein 3)
SB  - IM
MH  - Bile Acids and Salts/*pharmacology
MH  - Cell Culture Techniques
MH  - Cholestasis/*genetics/metabolism/*pathology
MH  - Gastrointestinal Agents/*pharmacology
MH  - Hep G2 Cells
MH  - Humans
MH  - Multidrug Resistance-Associated Proteins/*genetics/metabolism
MH  - RNA, Messenger/metabolism
OTO - NOTNLM
OT  - ABC transporters
OT  - Bile acids
OT  - Cholestasis
OT  - MRP3
OT  - MRP4
EDAT- 2021/02/15 06:00
MHDA- 2022/02/02 06:00
CRDT- 2021/02/14 20:27
PHST- 2020/12/03 00:00 [received]
PHST- 2021/01/31 00:00 [revised]
PHST- 2021/02/03 00:00 [accepted]
PHST- 2021/02/15 06:00 [pubmed]
PHST- 2022/02/02 06:00 [medline]
PHST- 2021/02/14 20:27 [entrez]
AID - S1665-2681(21)00024-7 [pii]
AID - 10.1016/j.aohep.2021.100325 [doi]
PST - ppublish
SO  - Ann Hepatol. 2021 Sep-Oct;24:100325. doi: 10.1016/j.aohep.2021.100325. Epub 2021 
      Feb 11.