PXD044587
PXD044587 is an original dataset announced via ProteomeXchange.
Dataset Summary
Title | Fasting upregulates the monocarboxylate transporter Mct1 at the rat blood-brain barrier through Ppar d activation |
Description | Fasting is increasingly recognized as a potential therapeutic intervention in the field of neurology and psychiatry. However, its impact upon the blood-brain barrier (BBB), which strictly regulates the cerebral uptake of a wide range of endogenous compounds and drugs, is unknown. In this study we used a combination of in vivo and in vitro experiments to assess the response of the brain endothelium in rats that were fed ad libitum or fasted for one to three days. Fasting did not change the expression of the main drug efflux ATP-binding cassette transporters or P-glycoprotein activity at the BBB but modulated a restrictive set of solute carrier transporters. These included the monocarboxylate transporter Mct1, which is pivotal for the cerebral uptake of ketone bodies and thus for brain adaptation to fasting. Transcriptional profiling of freshly isolated brain endothelial cells showed that Ppar d, a major lipid sensor, was selectively activated in response to fasting. In primary cultured rat brain endothelial cells, pharmacological agonists and free fatty acids selectively activated Ppar d, resulting in the upregulation of Mct1 expression at the transcriptional and protein level. This was confirmed in vivo, by showing that dosing rats with a specific Ppar d antagonist blocked the upregulation of Mct1 expression and activity induced by fasting. Altogether, our study describes for the first time a selective adaptive response of the brain vasculature to fasting and opens new perspectives for the metabolic manipulation of the BBB in the healthy or diseased brain. To further confirm that the Ppar d pathway is active brain endothelial cells, we exposed pc-CECs to GW0742 in the presence or not of GSK0660 for 48 hours and analyzed the cell lysate using non-targeted quantitative proteomics (n=3). |
HostingRepository | jPOST |
AnnounceDate | 2024-08-15 |
AnnouncementXML | Submission_2024-08-14_08:00:24.085.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | David Gomez-Zepeda |
SpeciesList | scientific name: cellular organisms; NCBI TaxID: 131567; |
ModificationList | S-carboxamidomethyl-L-cysteine; alpha-amino acetylated residue; L-methionine sulfoxide |
Instrument | instrument |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
---|---|---|---|
0 | 2023-08-15 04:24:33 | ID requested | |
⏵ 1 | 2024-08-14 08:00:25 | announced |
Publication List
Chasseigneaux S, Cochois-Gu, é, gan V, Lecorgne L, Lochus M, Nicolic S, Blugeon C, Jourdren L, Gomez-Zepeda D, Tenzer S, Sanquer S, Nivet-Antoine V, Menet MC, Laplanche JL, Decl, è, ves X, Cisternino S, Saubam, é, a B, activation. Fluids Barriers CNS, 21(1):33(2024) [pubmed] |
Keyword List
submitter keyword: Blood-Brain Barrier, Fasting, Mct1, Ppar d, Endothelial cells |
Contact List
David Gomez-Zepeda, Stefan Tenzer | |
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lab head | |
David Gomez-Zepeda | |
contact affiliation | HI-TRON, DKFZ |
dataset submitter |
Full Dataset Link List
jPOST dataset URI |
Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.jpostdb.org/JPST002293/ |