PXD024116-1

PXD024116 is an original dataset announced via ProteomeXchange.

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

Revision	Datetime	Status	ChangeLog Entry
0	2021-02-10 08:23:06	ID requested
⏵ 1	2024-10-07 13:37:43	announced

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;

submitter keyword: mouse, Q-Exactive, Phospholipids/Biosynthesis, Glycerophospholipids, Vascular Biology/Endothelial Cells, Plasmalogens, Peroxisomes

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

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PRIDE project URI

• PRIDE
  1. PXD024116
     1. Label: PRIDE project
     2. Name: Endothelial ether lipids link blood vessels to neurodegeneration