Red Cell Proteasome Modulation by Storage, Redox Metabolism and Transfusion

Overview

Journal Blood Transfus

Specialty Hematology

Date 2020 Dec 2

PMID 33263521

Citations 15

Authors

Vassilis L Tzounakas

Monika Dzieciatkowska

Alkmini T Anastasiadi

Dimitrios G Karadimas

Athina Vergaki

Panagiotis Siourounis

Konstantinos Stamoulis

Issidora S Papassideri

Anastasios G Kriebardis

Angelo DAlessandro

Marianna H Antonelou

Affiliations

Soon will be listed here.

Abstract

Background: Proteasomes are proteolytic complexes with prominent roles in the control of protein homeostasis and cellular viability. However, little is known about the effects of storage and glucose-6-phosphate dehydrogenase deficiency (G6PD) on the activity and topology of red blood cell (RBC) proteasomes.

Materials And Methods: We investigated the concentration (by GeLC-MS proteomics analysis and immunoblotting), activity (by using peptide substrates and proteasome inhibitors), and subcellular/extracellular distribution (following cell fractionation and isolation of extracellular vesicles, respectively) of RBC proteasomes in fresh blood and RBCs from control and G6PD donors following storage in leukoreduced units. RBC proteasome activity was also tested in transfusion-mimicking conditions in vitro.

Results: Stored RBCs were characterised by decreased cytosolic proteasome activity compared to fresh RBCs but increased membrane activity and protein concentration levels. Active proteasomes along with other "repair or destroy" proteins are recruited to the membrane during storage. A proportion of them is released in the supernatant in soluble form or inside extracellular vesicles. Significantly increased enzymatic activity and release of proteasomes were observed in G6PD vs control RBCs. Similar variations were observed in stress protein biomarkers at the G6PD membrane. The proteasome profile (mainly the caspase-like activity) had significant correlations with the G6PD metabolome and quality markers of the RBC units. The storage-induced modifications in the proteasome activities were only partly restored in transfusion-mimicking conditions.

Discussion: Storage conditions and G6PD deficiency affect (individually and in synergy) the abundance, distribution, activity, and release of RBC proteasomes. The partial irreversibility of these effects in transfusion-mimicking conditions demands further investigation of their clinical impact on transfusion outcomes.

Citing Articles

Molecular modifications to mitigate oxidative stress and improve red blood cell storability.

Anastasiadi A, Stamoulis K, Kriebardis A, Tzounakas V Front Physiol. 2024; 15:1499308.

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It's in your blood: The impact of age, sex, genetic factors and exposures on stored red blood cell metabolism.

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Biological and genetic determinants of glycolysis: Phosphofructokinase isoforms boost energy status of stored red blood cells and transfusion outcomes.

Nemkov T, Stephenson D, Earley E, Keele G, Hay A, Key A Cell Metab. 2024; 36(9):1979-1997.e13.

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Effect of leukoreduction on the omics phenotypes of canine packed red blood cells during refrigerated storage.

Miglio A, Rocconi F, Cremoni V, DAlessandro A, Reisz J, Maslanka M J Vet Intern Med. 2024; 38(3):1498-1511.

PMID: 38553798 PMC: 11099828. DOI: 10.1111/jvim.17031.

Effect of leukoreduction on the metabolism of equine packed red blood cells during refrigerated storage.

Miglio A, Rocconi F, Cremonini V, DAlessandro A, Reisz J, Maslanka M J Vet Intern Med. 2024; 38(2):1185-1195.

PMID: 38406982 PMC: 10937500. DOI: 10.1111/jvim.17015.

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