Phosphoproteomics and morphology of stored human red blood cells treated by protein tyrosine phosphatases inhibitor.

Autor:	Bardyn M; Laboratoire de Recherche sur les Produits Sanguins, Transfusion Interrégionale CRS, Epalinges, Switzerland., Crettaz D; Laboratoire de Recherche sur les Produits Sanguins, Transfusion Interrégionale CRS, Epalinges, Switzerland., Rappaz B; Biomolecular Screening Facility, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland., Hamelin R; Proteomics Core Facility, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland., Armand F; Proteomics Core Facility, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland., Tissot JD; Laboratoire de Recherche sur les Produits Sanguins, Transfusion Interrégionale CRS, Epalinges, Switzerland., Turcatti G; Biomolecular Screening Facility, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland., 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 and University of Lausanne, Lausanne, Switzerland.; Institute of Pharmaceutical Sciences of Western Switzerland, University of Geneva, Geneva, Switzerland.
Jazyk:	angličtina
Zdroj:	Blood advances [Blood Adv] 2024 Jan 09; Vol. 8 (1), pp. 1-13.
DOI:	10.1182/bloodadvances.2023009964
Abstrakt:	Abstract: The process of protein phosphorylation is involved in numerous cell functions. In particular, phosphotyrosine (pY) has been reported to play a role in red blood cell (RBC) functions, including the cytoskeleton organization. During their storage before transfusion, RBCs suffer from storage lesions that affect their energy metabolism and morphology. This study investigated the relationship between pY and the storage lesions. To do so, RBCs were treated (in the absence of calcium) with a protein tyrosine phosphatase inhibitor (orthovanadate [OV]) to stimulate phosphorylation and with 3 selective kinase inhibitors (KIs). Erythrocyte membrane proteins were studied by western blot analyses and phosphoproteomics (data are available via ProteomeXchange with identifier PXD039914) and cell morphology by digital holographic microscopy. The increase of pY triggered by OV treatment (inducing a global downregulation of pS and pT) disappeared during the storage. Phosphoproteomic analysis identified 609 phosphoproteins containing 1752 phosphosites, of which 41 pY were upregulated and 2 downregulated by OV. After these phosphorylation processes, the shape of RBCs shifted from discocytes to spherocytes, and the addition of KIs partially inhibited this transition. The KIs modulated either pY or pS and pT via diverse mechanisms related to cell shape, thereby affecting RBC morphology. The capacity of RBCs to maintain their function is central in transfusion medicine, and the presented results contribute to a better understanding of RBC biology. (© 2023 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)
Databáze:	MEDLINE
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