Evidence map›Paper›PMID 27193034›Full record

ArticleJournal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism2017

PPAR-α, a lipid-sensing transcription factor, regulates blood-brain barrier efflux transporter expression.

Vijay R More, Christopher R Campos, Rebecca A Evans, Keith D Oliver, Gary Ny Chan, David S Miller, Ronald E Cannon

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed
1.7field-weighted citation impact, top 14% 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

32 citing papers in PubMed, 61 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Article
  5. Review
  6. Article
  7. Article
  8. Article
  9. Article
  10. The multifaceted roles of activating transcription factor 3 (ATF3) in inflammatory responses - Potential target to regulate neuroinflammation in acute brain injury.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2023
    Review
  11. Review
  12. Article
  13. Review
  14. Article
  15. Regulation of P-Glycoprotein in the Brain.International journal of molecular sciences · 2022
    Review
  16. Review
  17. Article
  18. Concentration-dependent effects of chlorpyrifos oxon on peroxisome proliferator-activated receptor signaling in MCF-7 cells.Toxicology in vitro : an international journal published in association with BIBRA · 2022
    Article
  19. Review
  20. Review
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

7 authors at 1 institution in 1 country.

Vijay R MoreSignal Transduction Laboratory, National Institute of Environmental Health Sciences (NIEHS), National Institute of Health, Research Triangle Park, NC, USA.
Christopher R CamposSignal Transduction Laboratory, National Institute of Environmental Health Sciences (NIEHS), National Institute of Health, Research Triangle Park, NC, USA.
Rebecca A EvansSignal Transduction Laboratory, National Institute of Environmental Health Sciences (NIEHS), National Institute of Health, Research Triangle Park, NC, USA.
Keith D OliverSignal Transduction Laboratory, National Institute of Environmental Health Sciences (NIEHS), National Institute of Health, Research Triangle Park, NC, USA.
Gary Ny ChanSignal Transduction Laboratory, National Institute of Environmental Health Sciences (NIEHS), National Institute of Health, Research Triangle Park, NC, USA.
David S MillerSignal Transduction Laboratory, National Institute of Environmental Health Sciences (NIEHS), National Institute of Health, Research Triangle Park, NC, USA.
Ronald E CannonSignal Transduction Laboratory, National Institute of Environmental Health Sciences (NIEHS), National Institute of Health, Research Triangle Park, NC, USA.
National Institute of Environmental Health Sciences · US

Funding

Cellular Mechanisms Of Xenobiotic TransportZIAES080048 · NIEHS · NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES · PI CANNON, RONALD E. · 2009 to 2016
$10.3M
6 · The paper itself

Abstract

Lipid sensor peroxisome proliferator-activated receptor alpha (PPAR- α) is the master regulator of lipid metabolism. Dietary release of endogenous free fatty acids, fibrates, and certain persistent environmental pollutants, e.g. perfluoroalkyl fire-fighting foam components, are peroxisome proliferator-activated receptor alpha ligands. Here, we define a role for peroxisome proliferator-activated receptor alpha in regulating the expression of three ATP-driven drug efflux transporters at the rat and mouse blood-brain barriers: P-glycoprotein (Abcb1), breast cancer resistance protein (Bcrp/Abcg2), and multidrug resistance-associated protein 2 (Mrp2/Abcc2). Exposing isolated rat brain capillaries to linoleic acid, clofibrate, or PKAs increased the transport activity and protein expression of the three ABC transporters. These effects were blocked by the PPAR- α antagonist, GW6471. Dosing rats with 20 mg/kg or 200 mg/kg of clofibrate decreased the brain accumulation of the P-glycoprotein substrate, verapamil, by 50% (in situ brain perfusion; effects blocked by GW6471) and increased P-glycoprotein expression and activity in capillaries ex vivo. Fasting C57Bl/6 wild-type mice for 24 h increased both serum lipids and brain capillary P-glycoprotein transport activity. Fasting did not alter P-glycoprotein activity in PPAR- α knockout mice. These results indicate that hyperlipidemia, lipid-lowering fibrates and exposure to certain fire-fighting foam components activate blood-brain barrier peroxisome proliferator-activated receptor alpha, increase drug efflux transporter expression and reduce drug delivery to the brain.

Indexed as

Gene Expression RegulationAlkanesulfonic AcidsAnimalsATP-Binding Cassette, Sub-Family C ProteinsATP-Binding Cassette TransportersATP Binding Cassette Transporter, Subfamily B, Member 1ATP Binding Cassette Transporter, Subfamily G, Member 2Biological TransportBlood-Brain BarrierBrainCapillariesClofibrateFastingFluorocarbonsLinoleic AcidMaleAlkanesulfonic AcidsATP-Binding Cassette, Sub-Family C ProteinsATP-Binding Cassette TransportersATP Binding Cassette Transporter, Subfamily B, Member 1ATP Binding Cassette Transporter, Subfamily G, Member 2ClofibrateFluorocarbonsGW 6471Linoleic AcidMultidrug Resistance-Associated Protein 2Oxazolesperfluorooctane sulfonic acidPPAR alphaTyrosineBlood–brain barrierfastingfibrateP-glycoproteinPPAR

Identifiers

PMID27193034
PMCPMC5453444
OpenAlexW2398366925

What OpenQuestion holds

Textmetadata
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.