Evidence map›Paper›PMID 39322411›Full record

ArticleMolecular pharmacology2024

Identification of NanoLuciferase Substrates Transported by Human ABCB1 and ABCG2 and Their Zebrafish Homologs at the Blood-Brain Barrier.

John A Quinlan, Sashank Sabbineni, Robert W Robey, Crystal C Lipsey, Collin T Inglut, Joanna R Thomas, Joel R Walker, Wenhui Zhou, Huang-Chiao Huang, Michael M Gottesman

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular pharmacology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
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

1 citing paper in PubMed.

  1. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors.

John A QuinlanFischell Department of Bioengineering, University of Maryland, College Park, Maryland (J.A.Q., C.T.I., H.-C.H.); Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland (J.A.Q., S.S., R.W.R., C.C.L., C.T.I., J.R.T., M.M.G.); and Promega Corporation, San Luis Obispo, California (J.R.W., W.Z.).ORCID 0000-0002-8547-1535
Sashank SabbineniFischell Department of Bioengineering, University of Maryland, College Park, Maryland (J.A.Q., C.T.I., H.-C.H.); Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland (J.A.Q., S.S., R.W.R., C.C.L., C.T.I., J.R.T., M.M.G.); and Promega Corporation, San Luis Obispo, California (J.R.W., W.Z.).
Robert W RobeyFischell Department of Bioengineering, University of Maryland, College Park, Maryland (J.A.Q., C.T.I., H.-C.H.); Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland (J.A.Q., S.S., R.W.R., C.C.L., C.T.I., J.R.T., M.M.G.); and Promega Corporation, San Luis Obispo, California (J.R.W., W.Z.).ORCID 0000-0002-0857-3650
Crystal C LipseyFischell Department of Bioengineering, University of Maryland, College Park, Maryland (J.A.Q., C.T.I., H.-C.H.); Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland (J.A.Q., S.S., R.W.R., C.C.L., C.T.I., J.R.T., M.M.G.); and Promega Corporation, San Luis Obispo, California (J.R.W., W.Z.).ORCID 0000-0003-0494-7624
Collin T InglutFischell Department of Bioengineering, University of Maryland, College Park, Maryland (J.A.Q., C.T.I., H.-C.H.); Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland (J.A.Q., S.S., R.W.R., C.C.L., C.T.I., J.R.T., M.M.G.); and Promega Corporation, San Luis Obispo, California (J.R.W., W.Z.).ORCID 0000-0002-8407-2575
Joanna R ThomasFischell Department of Bioengineering, University of Maryland, College Park, Maryland (J.A.Q., C.T.I., H.-C.H.); Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland (J.A.Q., S.S., R.W.R., C.C.L., C.T.I., J.R.T., M.M.G.); and Promega Corporation, San Luis Obispo, California (J.R.W., W.Z.).ORCID 0000-0002-0508-7358
Joel R WalkerFischell Department of Bioengineering, University of Maryland, College Park, Maryland (J.A.Q., C.T.I., H.-C.H.); Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland (J.A.Q., S.S., R.W.R., C.C.L., C.T.I., J.R.T., M.M.G.); and Promega Corporation, San Luis Obispo, California (J.R.W., W.Z.).
Wenhui ZhouFischell Department of Bioengineering, University of Maryland, College Park, Maryland (J.A.Q., C.T.I., H.-C.H.); Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland (J.A.Q., S.S., R.W.R., C.C.L., C.T.I., J.R.T., M.M.G.); and Promega Corporation, San Luis Obispo, California (J.R.W., W.Z.).
Huang-Chiao HuangFischell Department of Bioengineering, University of Maryland, College Park, Maryland (J.A.Q., C.T.I., H.-C.H.); Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland (J.A.Q., S.S., R.W.R., C.C.L., C.T.I., J.R.T., M.M.G.); and Promega Corporation, San Luis Obispo, California (J.R.W., W.Z.).ORCID 0000-0002-5406-0733
Michael M GottesmanFischell Department of Bioengineering, University of Maryland, College Park, Maryland (J.A.Q., C.T.I., H.-C.H.); Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland (J.A.Q., S.S., R.W.R., C.C.L., C.T.I., J.R.T., M.M.G.); and Promega Corporation, San Luis Obispo, California (J.R.W., W.Z.) mgottesman@nih.gov.ORCID 0000-0001-8908-2097

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

ATP-binding cassette (ABC) transporters expressed at the blood-brain barrier (BBB) impede delivery of therapeutic agents to the brain, including agents to treat neurodegenerative diseases and primary and metastatic brain cancers. Two transporters, ABCB1 and ABCG2, are highly expressed at the BBB and are responsible for the efflux of numerous clinically useful chemotherapeutic agents, including irinotecan, paclitaxel, and doxorubicin. Based on a previous mouse model, we have generated transgenic zebrafish in which expression of NanoLuciferase (NanoLuc) is controlled by the promoter of glial fibrillary acidic protein, leading to expression in zebrafish glia. To identify agents that disrupt the BBB, including inhibitors of ABCB1 and ABCG2, we identified NanoLuc substrates that are also transported by ABCB1, ABCG2, and their zebrafish homologs. These substrates will elevate the amount of bioluminescent light produced in the transgenic zebrafish with BBB disruption. We transfected HEK293 cells with NanoLuc and either human ABCB1, ABCG2, or their zebrafish homologs Abcb4 or Abcg2a, respectively, that are expressed at the zebrafish BBB. We evaluated the luminescence and transporter substrate status of 16 NanoLuc substrates. We identified eight substrates that were efficiently pumped out by ABCB1, six by Abcb4, seven by ABCG2, and seven by Abcg2a. These data will aid in the development of a transgenic zebrafish model of the BBB to identify novel BBB disruptors and should prove useful in the development of other animal models that use NanoLuc as a reporter. SIGNIFICANCE STATEMENT: The ATP-binding cassette (ABC) transporters ABCB1 and ABCG2 at the blood-brain barrier (BBB) hinder pharmacological treatment of brain-related diseases. Consequently, there is a need for tools to identify BBB disruptors. This study screened 16 NanoLuciferase substrates, identifying the brightest and those that were transported by human and zebrafish ABC transporters at the BBB. This work supports and complements development of a transgenic zebrafish model, in which NanoLuciferase is expressed within glial cells, enabling detection of BBB disruption.

Indexed as

Animals, Genetically ModifiedATP Binding Cassette Transporter, Subfamily BATP Binding Cassette Transporter, Subfamily G, Member 2Blood-Brain BarrierZebrafishZebrafish ProteinsAnimalsATP-Binding Cassette Sub-Family B Member 4ATP-Binding Cassette TransportersATP Binding Cassette Transporter, Subfamily B, Member 1Biological TransportHEK293 CellsHumansNeoplasm ProteinsABCB1 protein, humanAbcb4 protein, zebrafishABCG2 protein, humanATP-Binding Cassette Sub-Family B Member 4ATP-Binding Cassette TransportersATP Binding Cassette Transporter, Subfamily BATP Binding Cassette Transporter, Subfamily B, Member 1ATP Binding Cassette Transporter, Subfamily G, Member 2Neoplasm ProteinsZebrafish Proteins

Identifiers

PMID39322411
PMCPMC11585257

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