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PXD001186 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleA role for CPT1A to prevent blood vessel permeability revealed by in depth proteomics
DescriptionEndothelial cells (ECs) line the inner wall of blood vessels and maintain vascular stability. Vascular stability alteration is a hallmark of pathologies such as cancer and thrombosis. A role for fatty acid oxidation (FAO) in this process is unknown. Integrating MS-proteomics and metabolic modeling revealed that FAO increases when ECs cultured on matrigel are assembled into a fully formed network. Inhibition of CPT1A in ECs, a limiting enzyme in FAO, results in disruption of this network. Acute CPT1A inhibition reduces cellular ATP levels and oxygen consumption, which can be restored replenishing the tricarboxylic acid cycle (TCAc). Phosphoproteomic changes upon acute CPT1A inhibition evoked those triggered by thrombin, a potent inducer of EC permeability through calcium signaling. Indeed, CPT1A inhibition increased EC permeability and vascular leakage, which were restored replenishing the TCAc or, partially, inhibiting calcium influx. Our study shows the possibility of altering FAO to interfere with ECs in diseases.
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterSara Zanivan
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListphosphorylated residue
InstrumentLTQ Orbitrap Elite
Dataset History
RevisionDatetimeStatusChangeLog Entry
02014-07-30 05:17:43ID requested
12015-01-28 07:58:37announced
22018-03-08 00:09:32announcedUpdated publication reference for PubMed record(s): 25573745.
Publication List
Patella F, Schug ZT, Persi E, Neilson LJ, Erami Z, Avanzato D, Maione F, Hernandez-Fernaud JR, Mackay G, Zheng L, Reid S, Frezza C, Giraudo E, Fiorio Pla A, Anderson K, Ruppin E, Gottlieb E, Zanivan S, Proteomics-based metabolic modeling reveals that fatty acid oxidation (FAO) controls endothelial cell (EC) permeability. Mol Cell Proteomics, 14(3):621-34(2015) [pubmed]
Keyword List
curator keyword: Biomedical
submitter keyword: SILAC, label-free, FAO, CPT1A, human, endothelial cells
Contact List
Sara Zanivan
contact affiliationCRUK Beatson Institute
contact emails.zanivan@beatson.gla.ac.uk
lab head
Sara Zanivan
contact affiliationVascular Proteomics
contact emails.zanivan@beatson.gla.ac.uk
dataset submitter
Full Dataset Link List
Dataset FTP location
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