Evidence map›Paper›PMID 28405913›Full record

ArticlePharmaceutical research2017

In Vitro Transport Activity and Trafficking of MRP2/ABCC2 Polymorphic Variants.

Xia Wen, Melanie S Joy, Lauren M Aleksunes

Open access · greenAbstract read
In one paragraph

Article in Pharmaceutical research, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed, 1 pooled it
1.5field-weighted citation impact, top 16% 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

14 citing papers in PubMed, 1 synthesis or guideline pooled it, 22 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. Article
  5. Article
  6. Case Report: Three novel pathogenicFrontiers in genetics · 2022
    Article
  7. Article
  8. Article
  9. Review
  10. Article
  11. Article
  12. In vitro Transport Ability ofOncoTargets and therapy · 2020
    Article
  13. Article
  14. Article
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

3 authors at 2 institutions in 1 country.

Xia WenDepartment of Pharmacology and Toxicology, Rutgers University Ernest Mario School of Pharmacy, 170 Frelinghuysen Road, Piscataway, New Jersey, 08854, USA.
Melanie S JoyDepartment of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado, Aurora, Colorado, 80045, USA.
Lauren M AleksunesDepartment of Pharmacology and Toxicology, Rutgers University Ernest Mario School of Pharmacy, 170 Frelinghuysen Road, Piscataway, New Jersey, 08854, USA. aleksunes@eohsi.rutgers.edu.
Rutgers, The State University of New Jersey · USUniversity of Montana · US

Funding

Translational Research Support CoreP30ES005022 · NIEHS · UNIV OF MED/DENT NJ-R W JOHNSON MED SCH · PI ROBERT John LAUMBACH · 1988 to 2026
$47.4M
Drug Metabolizing Enzyme and Transporter Function in Chronic Kidney DiseaseR01GM107122 · NIGMS · UNIVERSITY OF COLORADO DENVER · PI JOY, MELANIE S, NOLIN, THOMAS DOUGLAS · 2014 to 2018
$2.3M
Disposition of Environmental Chemicals During PregnancyR01ES020522 · NIEHS · RUTGERS, THE STATE UNIV OF N.J. · PI ALEKSUNES, LAUREN M · 2011 to 2015
$2.1M
Gene-Environment Interactions in Neurodegeneration: Role of Efflux TransportersR01ES021800 · NIEHS · RBHS-ROBERT WOOD JOHNSON MEDICAL SCHOOL · PI ALEKSUNES, LAUREN M, RICHARDSON, JASON R · 2014 to 2018
$1.9M
Protective Role of Mrp2 During Chemotherapy-Induced Kidney InjuryR00DK080774 · NIDDK · RUTGERS, THE STATE UNIV OF N.J. · PI ALEKSUNES, LAUREN M · 2009 to 2011
$695k
Pharmacokinetic and Pharmacogenomic Determinants of Cisplatin Kidney InjuryR21DK093903 · NIDDK · UNIVERSITY OF COLORADO DENVER · PI ALEKSUNES, LAUREN M, JOY, MELANIE S · 2012 to 2013
$423k
Protective Role of Mrp2 During Chemotherapy-Induced Kidney InjuryK99DK080774 · NIDDK · UNIVERSITY OF KANSAS MEDICAL CENTER · PI ALEKSUNES, LAUREN M · 2008 to 2008
$90k
NIDDK NIH HHS K99 DK080774NIDDK NIH HHS R00 DK080774NIDDK NIH HHS R21 DK093903NIEHS NIH HHS P30 ES005022NIEHS NIH HHS R01 ES020522NIEHS NIH HHS R01 ES021800NIGMS NIH HHS R01 GM107122
6 · The paper itself

Abstract

purposeMultidrug resistance-associated protein 2 (MRP2/ABCC2) is an efflux pump that removes drugs and chemicals from cells. We sought to characterize the expression, trafficking and in vitro activity of seven single nucleotide polymorphisms (SNPs) in the ABCC2 gene.

methodsABCC2 SNPs were generated using site-directed mutagenesis and stably expressed in Flp-In HEK293 cells, which allows targeted insertion of transgenes within the genome. Total and cell surface expression of MRP2 as well as accumulation of substrates (calcein AM and 5(6)-carboxy-2',7'-dichlorofluorescein diacetate, CDCF) were quantified in cells or inverted membrane vesicles expressing wild-type (WT) or variant forms.

resultsThe cell surface expression of the C-24T-, G1249A-, G3542T-, T3563A-, C3972T- and G4544A-MRP2 variants was similar to WT-MRP2. While expression was similar, transport of calcein AM was enhanced in cells expressing the G3542T-, T3563A-, C3972T-, and G4544A-MRP2 variants. By comparison, cells expressing the C2366T-MRP2 variant had 40-50% lower surface expression, which increased the accumulation of calcein AM up to 3-fold. Accumulation of CDCF in inverted membrane vesicles expressing the C2366T-MRP2 variant was also reduced by 50%. In addition, the G1249A-MRP2 variant had decreased transport of CDCF.

conclusionsTaken together, these data demonstrate that genetic variability in the ABCC2 gene influences the in vitro expression, trafficking, and transport activity of MRP2.

Indexed as

ATP-Binding Cassette, Sub-Family C ProteinsGene ExpressionGenetic VariationHEK293 CellsHumansMultidrug Resistance-Associated Protein 2MutationPolymorphism, Single NucleotideProtein TransportABCC2 protein, humanATP-Binding Cassette, Sub-Family C ProteinsMultidrug Resistance-Associated Protein 2ABCC2MRP2SNPtransportervariant

Identifiers

PMID28405913
PMCPMC5500460
OpenAlexW2607470662

What OpenQuestion holds

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Registered trials

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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.