PXD024116-1
PXD024116 is an original dataset announced via ProteomeXchange.
Dataset Summary
Title | Endothelial ether lipids link blood vessels to neurodegeneration |
Description | Vascular disease contributes to neurodegeneration, which is associated with decreased blood pressure in older humans. Plasmalogens, ether phospholipids produced by peroxisomes, are decreased in Alzheimer’s disease, Parkinson’s disease and other neurodegenerative disorders. Here we show that endothelium-derived ether phospholipids affect blood pressure, behavior, and neurodegeneration in mice. In young adult mice, inducible endothelial-specific disruption of PexRAP, a peroxisomal enzyme required for ether lipid synthesis, unexpectedly decreased circulating plasmalogens. PexRAP Endothelial KnockOut (PEKO) mice responded normally to hindlimb ischemia but had lower blood pressure and increased plasma renin activity. In PEKO as compared to control mice, tyrosine hydroxylase was decreased in the locus coeruleus, which maintains blood pressure and arousal. PEKO mice moved less, slept more, and had impaired attention to and recall of environmental events as well as mild spatial memory deficits. In PEKO hippocampus, gliosis was increased and a plasmalogen associated with memory was decreased. Despite lower blood pressure, PEKO mice had generally normal homotopic functional connectivity by optical neuroimaging of the cerebral cortex. Decreased GSK3 phosphorylation, a marker of neurodegeneration, was detected in PEKO cerebral cortex. In a co-culture system, PexRAP knockdown in brain endothelial cells decreased GSK3 phosphorylation in co-cultured astrocytes that was rescued by incubation with the ether lipid alkylglycerol. Our findings suggest that the endothelium is a source of complex lipids that confer neuroprotection in mice. |
HostingRepository | PRIDE |
AnnounceDate | 2024-10-07 |
AnnouncementXML | Submission_2024-10-07_13:37:42.345.xml |
DigitalObjectIdentifier | https://dx.doi.org/10.6019/PXD024116 |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Supported dataset by repository |
PrimarySubmitter | Qiang Zhang |
SpeciesList | scientific name: Mus musculus (Mouse); NCBI TaxID: 10090; |
ModificationList | (R)-5-oxo-1,4-tetrahydrothiazine-3-carboxylic acid; acetylated residue; monohydroxylated residue; deamidated residue; iodoacetamide derivatized residue |
Instrument | Q Exactive HF |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
---|---|---|---|
0 | 2021-02-10 08:23:06 | ID requested | |
⏵ 1 | 2024-10-07 13:37:43 | announced |
Publication List
Spears LD, Adak S, Dong G, Wei X, Spyropoulos G, Zhang Q, Yin L, Feng C, Hu D, Lodhi IJ, Hsu FF, Rajagopal R, Noguchi KK, Halabi CM, Brier L, Bice AR, Lananna BV, Musiek ES, Avraham O, Cavalli V, Holth JK, Holtzman DM, Wozniak DF, Culver JP, Semenkovich CF, Endothelial ether lipids link the vasculature to blood pressure, behavior, and neurodegeneration. J Lipid Res, 62():100079(2021) [pubmed] |
10.1016/j.jlr.2021.100079; |
10.6019/PXD024116; |
Keyword List
submitter keyword: mouse, Q-Exactive, Phospholipids/Biosynthesis, Glycerophospholipids, Vascular Biology/Endothelial Cells, Plasmalogens, Peroxisomes |
Contact List
Clay Semenkovich | |
---|---|
contact affiliation | Washington University in St. Louis - School of Medicine Division of Endocrinology, Metabolism & Lipid Research |
contact email | csemenko@wustl.edu |
lab head | |
Qiang Zhang | |
contact affiliation | Washington University in St. Louis |
contact email | zhang.qiang@wustl.edu |
dataset submitter |
Full Dataset Link List
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PRIDE project URI |
Repository Record List
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