PXD038483

PXD038483 is an original dataset announced via ProteomeXchange.

Title	Targeting mitochondria in the aged vasculature with SS-31, a proteomic study of brain microvessels.
Description	Functional decline and structural alterations of the brain microvasculature are associated with cognitive impairment and development of dementias such as Alzheimer’s disease during aging. Although mechanisms of leading to microvascular changes during aging are not clear, the loss of mitochondria and reduced efficiency of remaining mitochondria appear to play a major role. While pharmacological agents which target mitochondria such as SS-31 have been shown to be effective in beneficial during aging and diseases, the full extent on mitochondrial- and non-mitochondrial proteins in the brain microvasculature has not been examined. We tested the hypothesis that attenuation of aging-associated changes in the brain microvascular proteome via targeting mitochondria represents a therapeutic option in the aging brain. We used male, aged (>18 months) C57Bl6/J mice treated with a mitochondria-targeted tetrapeptide, SS-31 or vehicle saline. Baseline cerebral blood flow (CBF) was determined using laser speckle imaging during the two-week treatment period. Then, isolated cortical microvessels (MVs), composed of end arterioles, capillaries, and venules, were used for Orbitrap Eclipse Tribrid mass spectrometry. Baseline CBF was similar between the groups, whereas bioinformatic analysis revealed substantial differences in protein abundance of cortical MVs between SS-31 and vehicle groups. Specifically, we identified 6,266 proteins in our data set from which 12% were mitochondrial or mitochondria associated. 107 of these proteins were significantly differentially expressed between the treatment and vehicle groups, and were associated with the oxidative phosphorylation, metabolism, antioxidant defense system, or mitochondrial dynamics. Administration of SS-31 also affected many non-mitochondrial proteins. Our findings suggest that mitochondria in the microvasculature represent a therapeutic target in the aging brain, and widespread changes in the proteome may underlie the mechanisms of rejuvenating actions of SS-31 in the aging phenotype.
HostingRepository	PRIDE
AnnounceDate	2024-01-26
AnnouncementXML	Submission_2024-01-26_07:01:39.044.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD038483
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Stephanie Byrum
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Eclipse

Revision	Datetime	Status	ChangeLog Entry
0	2022-12-01 03:41:04	ID requested
⏵ 1	2024-01-26 07:01:40	announced

10.6019/PXD038483;

Seman A, Chandra PK, Byrum SD, Mackintosh SG, Gies AJ, Busija DW, Rutkai I, Targeting mitochondria in the aged cerebral vasculature with SS-31, a proteomic study of brain microvessels. Geroscience, 45(5):2951-2965(2023) [pubmed]

10.1007/s11357-023-00845-y;

submitter keyword: brain, TMT,mitochondria, microvessels

Ibolya Rutkai
contact affiliation	Department of Pharmacology, School of Medicine, Tulane University, New Orleans, LA
contact email	irutkai@tulane.edu
lab head
Stephanie Byrum
contact affiliation	UAMS
contact email	sbyrum@uams.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD038483
     1. Label: PRIDE project
     2. Name: Targeting mitochondria in the aged vasculature with SS-31, a proteomic study of brain microvessels.