Evidence map›Paper›PMID 28298215›Full record

ArticleFluids and barriers of the CNS2017

Nrf2 signaling increases expression of ATP-binding cassette subfamily C mRNA transcripts at the blood-brain barrier following hypoxia-reoxygenation stress.

Kathryn Ibbotson, Joshua Yell, Patrick T Ronaldson

Open access · goldAbstract read
In one paragraph

Article in Fluids and barriers of the CNS, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed, 1 pooled it
1.6field-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

23 citing papers in PubMed, 1 synthesis or guideline pooled it, 35 citations in OpenAlex.

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  9. Impact ofFrontiers in pharmacology · 2023
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  12. Efficacy of Ulinastatin and Sulforaphane Alone or in Combination in Rat Model of Streptozotocin Diabetes Induced Vascular Dementia.Clinical psychopharmacology and neuroscience : the official scientific journal of the Korean College of Neuropsychopharmacology · 2021
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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 1 institution in 1 country.

Kathryn IbbotsonDepartment of Pharmacology and Toxicology, College of Pharmacy, University of Arizona, 1295 N. Martin Avenue, P.O. Box 210202, Tucson, 85721, AZ, USA.
Joshua YellDepartment of Pharmacology, College of Medicine, University of Arizona, 1501 N. Campbell Avenue, P.O. Box 245050, Tucson, AZ, 85724-5050, USA.
Patrick T RonaldsonDepartment of Pharmacology, College of Medicine, University of Arizona, 1501 N. Campbell Avenue, P.O. Box 245050, Tucson, AZ, 85724-5050, USA. pronald@email.arizona.edu.
University of Arizona · US

Funding

Targeting Blood-Brain Barrier Transporters to Treat Ischemic StrokeR01NS084941 · NINDS · UNIVERSITY OF ARIZONA · PI RONALDSON, PATRICK THOMAS · 2014 to 2024
$4.4M
NINDS NIH HHS R01 NS084941
6 · The paper itself

Abstract

backgroundStrategies to maintain BBB integrity in diseases with a hypoxia/reoxygenation (H/R) component involve preventing glutathione (GSH) loss from endothelial cells. GSH efflux transporters include multidrug resistance proteins (Mrps). Therefore, characterization of Mrp regulation at the BBB during H/R is required to advance these transporters as therapeutic targets. Our goal was to investigate, in vivo, regulation of Abcc1, Abcc2, and Abcc4 mRNA expression (i.e., genes encoding Mrp isoforms that transport GSH) by nuclear factor E2-related factor (Nrf2) using a well-established H/R model.

methodsFemale Sprague-Dawley rats (200-250 g) were subjected to normoxia (Nx, 21% O

resultsWe observed increased microvascular expression of Abcc1, Abcc2, and Abcc4 mRNA following H/R treatment with reoxygenation times of 10 min, 30 min, and 1 h and in animals treated with sulforaphane. Using a biotinylated Nrf2 probe, we observed an upward band shift in brain microvessels isolated from H/R animals or animals administered sulforaphane. ChIP studies showed increased Nrf2 binding to antioxidant response elements on Abcc1, Abcc2, and Abcc4 promoters following H/R or sulforaphane treatment, suggesting a role for Nrf2 signaling in Abcc gene regulation.

conclusionsOur data show increased Abcc1, Abcc2, and Abcc4 mRNA expression at the BBB in response to H/R stress and that Abcc gene expression is regulated by Nrf2 signaling. Since these Mrp isoforms transport GSH, these results may point to endogenous transporters that can be targeted for BBB protection during H/R stress. Experiments are ongoing to examine functional implications of Nrf2-mediated increases in Abcc transcript expression. Such studies will determine utility of targeting Mrp isoforms for BBB protection in diseases with an H/R component.

Indexed as

Hyperbaric OxygenationHypoxiaAnimalsAnticarcinogenic AgentsATP-Binding Cassette, Sub-Family C ProteinsBlood-Brain BarrierBrainChromatin ImmunoprecipitationDisease Models, AnimalElectrophoretic Mobility Shift AssayFemaleGene Expression RegulationIsothiocyanatesMicrovesselsNF-E2-Related Factor 2RatsAnticarcinogenic AgentsATP-Binding Cassette, Sub-Family C ProteinsIsothiocyanatesNfe2l2 protein, ratNF-E2-Related Factor 2RNA, MessengersulforaphaneSulfoxidesBlood–brain barrierEndothelial cellHypoxiaMultidrug resistance proteinsNrf2 signalingTransporters

Identifiers

PMID28298215
PMCPMC5353788
OpenAlexW2592591770

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.