Evidence map›Paper›PMID 20578149›Full record

ArticleHepatology (Baltimore, Md.)2010

Regulation of multidrug resistance-associated protein 2 by calcium signaling in mouse liver.

Laura N Cruz, Mateus T Guerra, Emma Kruglov, Albert Mennone, Celia R S Garcia, Ju Chen, Michael H Nathanson

Open access · greenAbstract read
In one paragraph

Article in Hepatology (Baltimore, Md.), 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.

0numbers the graph read from it
0cells of the map it votes in
29citing papers in PubMed
1.7field-weighted citation impact, top 17% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

29 citing papers in PubMed, 51 citations in OpenAlex.

  1. Article
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  11. IL-33 signalling in liver immune cells enhances drug-induced liver injury and inflammation.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2018
    Article
  12. Article
  13. Article
  14. InsP3 Signaling in Apicomplexan Parasites.Current topics in medicinal chemistry · 2017
    Review
  15. Article
  16. Calcium signaling and secretion in cholangiocytes.Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.] · 2015
    Review
  17. Novel therapeutic targets in primary biliary cirrhosis.Nature reviews. Gastroenterology & hepatology · 2015
    Review
  18. Article
  19. Article
  20. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 4 institutions in 2 countries.

Laura N CruzSection of Digestive Diseases, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520-8019, USA.
Mateus T Guerra
Emma Kruglov
Albert Mennone
Celia R S Garcia
Ju Chen
Michael H Nathanson
Yale University · USUniversidade de São Paulo · BRUniversidade Federal de Minas Gerais · BRUniversity of California, San Diego · US

Funding

Yale Liver CenterP30DK034989 · NIDDK · YALE UNIVERSITY · PI YASUKO IWAKIRI · 1986 to 2026
$31.1M
Translational CoreP01DK057751 · NIDDK · YALE UNIVERSITY · PI NATHANSON, MICHAEL H · 2001 to 2020
$25.6M
CALCIUM WAVES IN HEPATOCYTES--MECHANISMS AND EFFECTSR01DK045710 · NIDDK · YALE UNIVERSITY · PI NATHANSON, MICHAEL H · 1999 to 2014
$5.7M
Regulation of cholangiocytes by InsP3 receptor isoformsR01DK061747 · NIDDK · YALE UNIVERSITY · PI EHRLICH, BARBARA E., NATHANSON, MICHAEL H · 2003 to 2012
$3.4M
EXERCISE AND TYPE II DIABETES--ADHERENCE AND CVD RISKR01DK054710 · NIDDK · BAYLOR COLLEGE OF MEDICINE · PI GOODRICK, GEORGE KENNETH · 1999 to 2000
$288k
NIDDK NIH HHS DK34989NIDDK NIH HHS DK54710NIDDK NIH HHS DK57751NIDDK NIH HHS DK61747NIDDK NIH HHS P01 DK057751NIDDK NIH HHS P30 DK034989NIDDK NIH HHS R01 DK045710NIDDK NIH HHS R01 DK061747
6 · The paper itself

Abstract

unlabelledMultidrug resistance associated protein 2 (Mrp2) is a canalicular transporter responsible for organic anion secretion into bile. Mrp2 activity is regulated by insertion into the plasma membrane; however, the factors that control this are not understood. Calcium (Ca(2+)) signaling regulates exocytosis of vesicles in most cell types, and the type II inositol 1,4,5-triphosphate receptor (InsP(3)R2) regulates Ca(2+) release in the canalicular region of hepatocytes. However, the role of InsP(3)R2 and of Ca(2+) signals in canalicular insertion and function of Mrp2 is not known. The aim of this study was to determine the role of InsP(3)R2-mediated Ca(2+) signals in targeting Mrp2 to the canalicular membrane. Livers, isolated hepatocytes, and hepatocytes in collagen sandwich culture from wild-type (WT) and InsP(3)R2 knockout (KO) mice were used for western blots, confocal immunofluorescence, and time-lapse imaging of Ca(2+) signals and of secretion of a fluorescent organic anion. Plasma membrane insertion of green fluorescent protein (GFP)-Mrp2 expressed in HepG2 cells was monitored by total internal reflection microscopy. InsP(3)R2 was concentrated in the canalicular region of WT mice but absent in InsP(3)R2 KO livers, whereas expression and localization of InsP(3)R1 was preserved, and InsP(3)R3 was absent from both WT and KO livers. Ca(2+) signals induced by either adenosine triphosphate (ATP) or vasopressin were impaired in hepatocytes lacking InsP(3)R2. Canalicular secretion of the organic anion 5-chloromethylfluorescein diacetate (CMFDA) was reduced in KO hepatocytes, as well as in WT hepatocytes treated with 1,2-bis(o-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA). Moreover, the choleretic effect of tauroursodeoxycholic acid (TUDCA) was impaired in InsP(3)R2 KO mice. Finally, ATP increased GFP-Mrp2 fluorescence in the plasma membrane of HepG2 cells, and this also was reduced by BAPTA.

conclusionInsP(3)R2-mediated Ca(2+) signals enhance organic anion secretion into bile by targeting Mrp2 to the canalicular membrane.

Indexed as

Calcium SignalingAdenosine TriphosphateAnimalsATP-Binding Cassette, Sub-Family C ProteinsBileBilirubinCalciumEgtazic AcidHepatocytesInositol 1,4,5-Trisphosphate ReceptorsLiverMaleMiceMice, KnockoutMultidrug Resistance-Associated Protein 2Protein Isoforms1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acidAdenosine TriphosphateATP-Binding Cassette, Sub-Family C ProteinsBilirubinCalciumEgtazic AcidInositol 1,4,5-Trisphosphate ReceptorsMultidrug Resistance-Associated Protein 2Protein IsoformsTaurochenodeoxycholic Acidursodoxicoltaurine

Identifiers

PMID20578149
PMCPMC3025771
OpenAlexW2016628001

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.