Increase of Phosphoprotein Expressions in Amotosalen/UVA-Treated Platelet Concentrates.

Pathogen inactivation Phosphoproteomics Platelet Transfusion medicine

Journal

Transfusion medicine and hemotherapy : offizielles Organ der Deutschen Gesellschaft fur Transfusionsmedizin und Immunhamatologie
ISSN: 1660-3796
Titre abrégé: Transfus Med Hemother
Pays: Switzerland
ID NLM: 101176417

Informations de publication

Date de publication:
Apr 2024
Historique:
received: 04 08 2023
accepted: 05 11 2023
medline: 8 4 2024
pubmed: 8 4 2024
entrez: 8 4 2024
Statut: epublish

Résumé

Pathogen inactivation treatment (PIT) has been shown to alter platelet function, phenotype, morphology and to induce a faster aging of platelet concentrates (PCs). Key pieces of information are still missing to understand the impacts of PITs at the cellular level. This study investigated the impact of amotosalen/UVA on PCs, from a post-translational modifications (PTM) point of view. Phosphoproteomic analyses were conducted on resting platelets, right after the amotosalen/UVA treatment and compared with untreated PCs. A two-arm study setting was carried out to compare PIT (amotosalen/UVA) to untreated PCs, on day 1 post-donation. Based on a pool-and-split approach, 12 PCs were split into two groups (treated and untreated). Quantitative phosphoproteomics was performed using TMT technology to study the changes of phosphoproteins right after the PIT. A total of 3,906 proteins and 7,334 phosphosites were identified, and 2,473 proteins and 2,214 phosphosites were observed in at least 5 to 6 replicates. Compared to untreated platelets, PIT platelets exhibited an upregulation of the phosphorylation effects, with 109 phosphosites identified with a higher than 2-fold change. Two pathways were clearly identified. The mitogen activated protein kinases (MAPKs) cascade, which triggers the granule secretion and the activation of the pS15 HSPB1. One of the shape change pathways was also observed with the inhibition of the Threonine 18 and Serine 19 phosphorylations on myosin light chain (MLC) protein after the amotosalen/UVA treatment. This work provides a deep insight into the impact of amotosalen/UVA treatment from a phosphoprotein viewpoint on resting platelets. Clear changes in phosphorylation of proteins belonging to different platelet pathways were quantified. This discovery corroborates previous findings and fills missing parts of the effect of photochemical treatments on platelets.

Sections du résumé

Background UNASSIGNED
Pathogen inactivation treatment (PIT) has been shown to alter platelet function, phenotype, morphology and to induce a faster aging of platelet concentrates (PCs). Key pieces of information are still missing to understand the impacts of PITs at the cellular level.
Objectives UNASSIGNED
This study investigated the impact of amotosalen/UVA on PCs, from a post-translational modifications (PTM) point of view. Phosphoproteomic analyses were conducted on resting platelets, right after the amotosalen/UVA treatment and compared with untreated PCs.
Method UNASSIGNED
A two-arm study setting was carried out to compare PIT (amotosalen/UVA) to untreated PCs, on day 1 post-donation. Based on a pool-and-split approach, 12 PCs were split into two groups (treated and untreated). Quantitative phosphoproteomics was performed using TMT technology to study the changes of phosphoproteins right after the PIT.
Results UNASSIGNED
A total of 3,906 proteins and 7,334 phosphosites were identified, and 2,473 proteins and 2,214 phosphosites were observed in at least 5 to 6 replicates. Compared to untreated platelets, PIT platelets exhibited an upregulation of the phosphorylation effects, with 109 phosphosites identified with a higher than 2-fold change. Two pathways were clearly identified. The mitogen activated protein kinases (MAPKs) cascade, which triggers the granule secretion and the activation of the pS15 HSPB1. One of the shape change pathways was also observed with the inhibition of the Threonine 18 and Serine 19 phosphorylations on myosin light chain (MLC) protein after the amotosalen/UVA treatment.
Conclusions UNASSIGNED
This work provides a deep insight into the impact of amotosalen/UVA treatment from a phosphoprotein viewpoint on resting platelets. Clear changes in phosphorylation of proteins belonging to different platelet pathways were quantified. This discovery corroborates previous findings and fills missing parts of the effect of photochemical treatments on platelets.

Identifiants

DOI: 10.1159/000535060 PMID: 38584699 PMC: PMC10996061
pubmed: 38584699
doi: 10.1159/000535060
pii: 535060
pmc: PMC10996061
doi:

Types de publication

Journal Article

Langues

eng

Pagination

101-110

Informations de copyright

© 2024 The Author(s). Published by S. Karger AG, Basel.

Déclaration de conflit d'intérêts

The authors have no conflicts of interest to declare.

Auteurs

Charlotte Muret (C)

Laboratoire de Recherche sur Les Produits Sanguins, Transfusion Interrégionale CRS, Epalinges, Switzerland.

David Crettaz (D)

Laboratoire de Recherche sur Les Produits Sanguins, Transfusion Interrégionale CRS, Epalinges, Switzerland.

Lorenzo Alberio (L)

Division of Hematology and Central Hematology Laboratory, CHUV, Lausanne University Hospital (CHUV) and University of Lausanne (UNIL), Lausanne, Switzerland.

Michel Prudent (M)

Laboratoire de Recherche sur Les Produits Sanguins, Transfusion Interrégionale CRS, Epalinges, Switzerland.
Center for Research and Innovation in Clinical Pharmaceutical Sciences, Lausanne University Hospital (CHUV) and University of Lausanne (UNIL), Lausanne, Switzerland.
Institute of Pharmaceutical Sciences of Western Switzerland, University of Geneva, Geneva, Switzerland.

Classifications MeSH