Evidence map›Paper›PMID 37986908›Full record

ArticlebioRxiv : the preprint server for biology2023

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

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

Open access · greenAbstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing 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

0 citing papers in PubMed, 0 citations in OpenAlex.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors at 3 institutions in 1 country.

Collin T InglutFischell Department of Bioengineering, University of Maryland, College Park, MD 20742 (C.T.I., J.A.Q., H.-C.H.); Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892 (C.T.I., J.A.Q., R.W.R, J.R.T, M.M.G.), Promega Corporation, San Luis Obispo, CA, 93401 (J.R.W., W.Z.).ORCID 0000-0002-8407-2575
John A QuinlanFischell Department of Bioengineering, University of Maryland, College Park, MD 20742 (C.T.I., J.A.Q., H.-C.H.); Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892 (C.T.I., J.A.Q., R.W.R, J.R.T, M.M.G.), Promega Corporation, San Luis Obispo, CA, 93401 (J.R.W., W.Z.).ORCID 0000-0002-8547-1535
Robert W RobeyFischell Department of Bioengineering, University of Maryland, College Park, MD 20742 (C.T.I., J.A.Q., H.-C.H.); Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892 (C.T.I., J.A.Q., R.W.R, J.R.T, M.M.G.), Promega Corporation, San Luis Obispo, CA, 93401 (J.R.W., W.Z.).ORCID 0000-0002-0857-3650
Joanna R ThomasFischell Department of Bioengineering, University of Maryland, College Park, MD 20742 (C.T.I., J.A.Q., H.-C.H.); Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892 (C.T.I., J.A.Q., R.W.R, J.R.T, M.M.G.), Promega Corporation, San Luis Obispo, CA, 93401 (J.R.W., W.Z.).ORCID 0000-0002-0508-7358
Joel R WalkerFischell Department of Bioengineering, University of Maryland, College Park, MD 20742 (C.T.I., J.A.Q., H.-C.H.); Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892 (C.T.I., J.A.Q., R.W.R, J.R.T, M.M.G.), Promega Corporation, San Luis Obispo, CA, 93401 (J.R.W., W.Z.).ORCID 0000-0001-6855-2969
Wenhui ZhouFischell Department of Bioengineering, University of Maryland, College Park, MD 20742 (C.T.I., J.A.Q., H.-C.H.); Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892 (C.T.I., J.A.Q., R.W.R, J.R.T, M.M.G.), Promega Corporation, San Luis Obispo, CA, 93401 (J.R.W., W.Z.).ORCID 0000-0003-2178-3959
Huang-Chiao HuangFischell Department of Bioengineering, University of Maryland, College Park, MD 20742 (C.T.I., J.A.Q., H.-C.H.); Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892 (C.T.I., J.A.Q., R.W.R, J.R.T, M.M.G.), Promega Corporation, San Luis Obispo, CA, 93401 (J.R.W., W.Z.).ORCID 0000-0002-5406-0733
Michael M GottesmanFischell Department of Bioengineering, University of Maryland, College Park, MD 20742 (C.T.I., J.A.Q., H.-C.H.); Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892 (C.T.I., J.A.Q., R.W.R, J.R.T, M.M.G.), Promega Corporation, San Luis Obispo, CA, 93401 (J.R.W., W.Z.).ORCID 0000-0001-8908-2097
National Institutes of Health · USPromega (United States) · USNational Cancer Institute · US

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, P-glycoprotein (P-gp, 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 P-gp, 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, and expressed at the zebrafish BBB. We evaluated the luminescence of ten NanoLuc substrates, then screened the eight brightest to determine which are most efficiently effluxed by the ABC transporters. We identified one substrate efficiently pumped out by ABCB1, two by Abcb4, six by ABCG2, and four 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.

Identifiers

PMID37986908
PMCPMC10659404
OpenAlexW4387866992

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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.