The platelet proteasome and immunoproteasome are stable in buffy‐coat derived platelet concentrates for up to 7 days

Abstract

Objectives: Characterization of the proteasome and its stability in buffy-coat derived platelet concentrates (PCs) during storage.Background: The proteasome plays a key role in cell homeostasis by processing misfolded or abnormal proteins and regulating the levels and activities of a high number of proteins contributing to cell cycle, survival, and proliferation. Controversial data exist, whether inhibition of the proteasome affects platelet function. Little is known about function, expression, and stability of the proteasome in PCs during storage, and the potential role of the platelet proteasome in storage lesions.Study design and methods: PCs were produced by the buffy-coat method in additive solution and stored at room temperature under agitation. Platelet aggregation was monitored by light transmission aggregometry. Proteasome complexes were assessed by immunoprecipitation and immunoblotting, and proteasome activity was measured using fluorogenic substrates specific for the three different proteolytic activities over 7 days of storage. Results: Proteasome inhibition led to a decreased platelet aggregation response after activation with collagen, ADP, TRAP-6, and thrombin. There were no changes in the expression of the catalytic active subunits as well as the proteasome activity during storage of PCs, comparing baseline and day 7.Discussion: Platelet proteasome function is relevant for platelet aggregation in response to various agonists. The constitutive and stable expression of the active standard-and immunoproteasome in platelets makes it unlikely that loss of proteasome function is a relevant cause of storage lesions.

The platelet transcriptome and proteome in Alzheimer’s disease and aging: an exploratory cross-sectional study

“…Platelets have a dynamic transcriptome, and transcriptomic alterations occur in aging and several diseases with functional implications (Davizon-Castillo et al, 2020). We observed the dysregulation of several transcripts related to the ubiquitin-proteasomal Frontiers in Molecular Biosciences frontiersin.org system in AD and autophagy in aged platelets, two proteolytic pathways involved in the regulation of platelet function (Feng et al, 2014;Gupta et al, 2014;Ouseph et al, 2015;Colberg et al, 2021).…”

“…Platelets possess an active proteasome system (Klockenbusch et al, 2014), and its inhibition impairs platelet aggregation (Colberg et al, 2021). Besides regulating protein content, the ubiquitin-proteasome system in platelets is involved in cell signaling (Unsworth et al, 2019) and cytoskeleton remodeling following platelet activation (Gupta et al, 2014).…”