Evidence map›Paper›PMID 19172464›Full record

ArticleCurrent eye research2009

Molecular expression and functional evidence of a drug efflux pump (BCRP) in human corneal epithelial cells.

Pradeep K Karla, Ravinder Earla, Sagar H Boddu, Thomas P Johnston, Dhananjay Pal, Ashim Mitra

Open access · greenAbstract read
In one paragraph

Article in Current eye research, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed, 1 pooled it
3.0field-weighted citation impact, top 8% 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

26 citing papers in PubMed, 1 synthesis or guideline pooled it, 57 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Review
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  5. Review
  6. Nanotechnology for Topical Drug Delivery to the Anterior Segment of the Eye.International journal of molecular sciences · 2021
    Review
  7. Review
  8. Advances and limitations of drug delivery systems formulated as eye drops.Journal of controlled release : official journal of the Controlled Release Society · 2020
    Review
  9. Review
  10. Article
  11. Review
  12. Review
  13. Interaction Studies of Resolvin E1 Analog (RX-10045) with Efflux Transporters.Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics · 2015
    Article
  14. Article
  15. Novel strategies for anterior segment ocular drug delivery.Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics · 2013
    Review
  16. Article
  17. Article
  18. Article
  19. Prodrug strategies in ocular drug delivery.Medicinal chemistry (Shariqah (United Arab Emirates)) · 2012
    Review
  20. 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

6 authors at 1 institution in 1 country.

Pradeep K KarlaDivision of Pharmaceutical Sciences, School of Pharmacy, University of Missouri-Kansas City, Kansas City, Missouri 64110-2499, USA.
Ravinder Earla
Sagar H Boddu
Thomas P Johnston
Dhananjay Pal
Ashim Mitra
University of Missouri–Kansas City · US

Funding

Ocular Disposition of Antimicrobial AgentsR01EY009171 · NEI · UNIVERSITY OF MISSOURI KANSAS CITY · PI MITRA, ASHIM K. · 1992 to 2010
$3.0M
Transscleral Transport & Polymeric Delivery of Antibody & Steroids for Macular EdR01EY010659 · NEI · UNIVERSITY OF MISSOURI KANSAS CITY · PI MITRA, ASHIM K. · 1996 to 2010
$2.5M
NEI NIH HHS R01 EY009171NEI NIH HHS R01 EY010659NEI NIH HHS R01 EY09171-12, 13NEI NIH HHS R01 EY10659-10
6 · The paper itself

Abstract

purposeBreast Cancer Resistance Protein (BCRP) belongs to the family of efflux transporters involved in drug efflux leading to drug resistance. The objective of this study was to explore physical barriers for ocular drug absorption and to verify the presence and possible role of BCRP as a barrier for ocular drug resistance.

methodsTransfected human corneal epithelial cells (SV40-HCEC) were selected as an in vitro model for corneal epithelium with MDCKII-BCRP as positive control. [(3)H]-Mitoxantrone ([(3)H]-MTX), which is a proven substrate for organic anion transporter like BCRP, was selected as a model drug for functional expression studies. Fumetremorgin C (FTC), a known specific inhibitor for BCRP and GF120918, an inhibitor for BCRP and P-gp, were added to inhibit BCRP-mediated efflux. PGP-4008, a specific inhibitor of P-gp was used to delineate the contribution of P-gp. The mRNA extracted from cells was used for RT-PCR analysis and gene expression. Membrane fractions of SV40-HCEC and MDCKII-BCRP were used for immunoprecipitation followed by Western blot analysis.

resultsEfflux was inhibited significantly in the presence of FTC and GF120918. Dose-dependent inhibition of efflux by BCRP was noticed in SV40-HCEC and MDCKII-BCRP in the presence of FTC and GF120918, and the efflux was ATP-dependent. The metabolic inhibitor, 2,4-DNP, significantly inhibited efflux. No pH-dependent efflux was noticed except at pH 5.5. RT-PCR analysis indicated a unique and distinct band at approximately 429 bp, corresponding to BCRP in SV40-HCEC and MDCKII-BCRP cells. Western Blot analysis indicated a specific band at approximately 70 kDa in the membrane fraction of SV40-HCEC and MDCKII-BCRP cells.

conclusionsWe have demonstrated the expression of BCRP in human corneal epithelial cells and, for the first time, demonstrated its functional activity leading to drug efflux. RT-PCR and Western blot analysis further confirmed this finding.

Indexed as

AcetanilidesAcridinesATP-Binding Cassette TransportersATP Binding Cassette Transporter, Subfamily B, Member 1ATP Binding Cassette Transporter, Subfamily G, Member 2Blotting, WesternCells, CulturedCell Transformation, ViralDose-Response Relationship, DrugDrug Resistance, MultipleEpithelium, CornealGene Expression RegulationHumansHydrogen-Ion ConcentrationIndolesMitoxantroneABCG2 protein, humanAcetanilidesAcridinesATP-Binding Cassette TransportersATP Binding Cassette Transporter, Subfamily B, Member 1ATP Binding Cassette Transporter, Subfamily G, Member 2ElacridarIndolesMitoxantroneN-1-benzyl-2,3-dihydro-1H-pyrrolo(2,3-b)quinolin-4-yl-2-phenylacetamideNeoplasm ProteinsPyrrolesQuinolinesRNA, MessengerTetrahydroisoquinolinestryptoquivaline

Identifiers

PMID19172464
PMCPMC4406241
OpenAlexW2035308172

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.