Proteomics

Dataset Information

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Aging-related Alterations in mTOR Signaling Promote Platelet Hyperreactivity and Thrombosis

ABSTRACT: Isobaric labeling quantitative phospho proteomics uncovered differential site-specific protein phosphorylation within mTOR, Rho GTPase and MAPK systems in platelets from aged donors. Western blot confirmed constitutive activation of the mTOR pathway in platelets from both aged humans and mice, which was associated with increased aggregation compared to young controls. Inhibition of mTOR either with Torin 1 in aged humans, or genetic deletion in aged mice, reversed platelet hyperreactivity. Mechanistically, we noted increased levels of mitochondrial reactive oxygen species and Rac1 activation in resting platelets from aged mice, as well as increased p38 phosphorylation upstream of thromboxane generation following agonist stimulation.

INSTRUMENT(S): Orbitrap Fusion

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Blood Platelet, Platelet

SUBMITTER: Phillip Wilmarth  

LAB HEAD: Dr. Joe Aslan

PROVIDER: PXD049967 | Pride | 2025-05-25

REPOSITORIES: Pride

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ASLA-626-phospho_QC_checks.html Other
ASLA-626-phospho_edgeR.html Other
ASLA-626_humanplatelet_TiO2phos_TMT_43pt2ug_25cm_120min_10ACN_20181128_OT.raw Raw
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Publications

Aging-related alterations in mechanistic target of rapamycin signaling promote platelet hyperreactivity and thrombosis.

Portier Irina I   Manne Bhanu Kanth BK   Kosaka Yasuhiro Y   Tolley Neal D ND   Denorme Frederik F   Babur Özgün Ö   Reddy Ashok P AP   Wilmarth Phillip A PA   Aslan Joseph E JE   Weyrich Andrew S AS   Rondina Matthew T MT   Campbell Robert A RA  

Journal of thrombosis and haemostasis : JTH 20240606 9

<h4>Background</h4>Aging is an independent risk factor for the development of cardiovascular, thrombotic, and other chronic diseases. However, mechanisms of platelet hyperactivation in aging remain poorly understood.<h4>Objectives</h4>Here, we examine whether and how aging alters intracellular signaling in platelets to support platelet hyperactivity and thrombosis.<h4>Methods</h4>Quantitative mass spectrometry with tandem mass tag labeling systematically measured protein phosphorylation in plate  ...[more]

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