TY - JOUR

T1 - The effect of myeloperoxidase isoforms on biophysical properties of red blood cells

AU - Shamova, Ekaterina V.

AU - Gorudko, Irina V.

AU - Grigorieva, Daria V.

AU - Sokolov, Alexey V.

AU - Kokhan, Anatoli U.

AU - Melnikova, Galina B.

AU - Yafremau, Nikolai A.

AU - Gusev, Sergey A.

AU - Sveshnikova, Anastasia N.

AU - Vasilyev, Vadim B.

AU - Cherenkevich, Sergey N.

AU - Panasenko, Oleg M.

N1 - Funding Information: This work was partly supported by Russian Foundation for Basic Research (Grant 18-515-00004, Grant 17-54-04009), Belarusian Republican Foundation for Fundamental Research (Grant B18R-058) and Russian President’s grant MD-5133.2018.4. Publisher Copyright: © 2019, Springer Science+Business Media, LLC, part of Springer Nature. Copyright: Copyright 2020 Elsevier B.V., All rights reserved.

PY - 2020/1/1

Y1 - 2020/1/1

N2 - Myeloperoxidase (MPO), an oxidant-producing enzyme, stored in azurophilic granules of neutrophils has been recently shown to influence red blood cell (RBC) deformability leading to abnormalities in blood microcirculation. Native MPO is a homodimer, consisting of two identical protomers (monomeric MPO) connected by a single disulfide bond but in inflammatory foci as a result of disulfide cleavage monomeric MPO (hemi-MPO) can also be produced. This study investigated if two MPO isoforms have distinct effects on biophysical properties of RBCs. We have found that hemi-MPO, as well as the dimeric form, bind to the glycophorins A/B and band 3 protein on RBC’s plasma membrane, that lead to reduced cell resistance to osmotic and acidic hemolysis, reduction in cell elasticity, significant changes in cell volume, morphology, and the conductance of RBC plasma membrane ion channels. Furthermore, we have shown for the first time that both dimeric and hemi-MPO lead to phosphatidylserine (PS) exposure on the outer leaflet of RBC membrane. However, the effects of hemi-MPO on the structural and functional properties of RBCs were lower compared to those of dimeric MPO. These findings suggest that the ability of MPO protein to influence RBC’s biophysical properties depends on its conformation (dimeric or monomeric isoform). It is intriguing to speculate that hemi-MPO appearance in blood during inflammation can serve as a regulatory mechanism addressed to reduce abnormalities on RBC response, induced by dimeric MPO.

AB - Myeloperoxidase (MPO), an oxidant-producing enzyme, stored in azurophilic granules of neutrophils has been recently shown to influence red blood cell (RBC) deformability leading to abnormalities in blood microcirculation. Native MPO is a homodimer, consisting of two identical protomers (monomeric MPO) connected by a single disulfide bond but in inflammatory foci as a result of disulfide cleavage monomeric MPO (hemi-MPO) can also be produced. This study investigated if two MPO isoforms have distinct effects on biophysical properties of RBCs. We have found that hemi-MPO, as well as the dimeric form, bind to the glycophorins A/B and band 3 protein on RBC’s plasma membrane, that lead to reduced cell resistance to osmotic and acidic hemolysis, reduction in cell elasticity, significant changes in cell volume, morphology, and the conductance of RBC plasma membrane ion channels. Furthermore, we have shown for the first time that both dimeric and hemi-MPO lead to phosphatidylserine (PS) exposure on the outer leaflet of RBC membrane. However, the effects of hemi-MPO on the structural and functional properties of RBCs were lower compared to those of dimeric MPO. These findings suggest that the ability of MPO protein to influence RBC’s biophysical properties depends on its conformation (dimeric or monomeric isoform). It is intriguing to speculate that hemi-MPO appearance in blood during inflammation can serve as a regulatory mechanism addressed to reduce abnormalities on RBC response, induced by dimeric MPO.

KW - Dimeric myeloperoxidase

KW - Inflammation

KW - Monomeric myeloperoxidase

KW - Phosphatidylserine

KW - RBC

UR - http://www.scopus.com/inward/record.url?scp=85075302881&partnerID=8YFLogxK

U2 - 10.1007/s11010-019-03654-0

DO - 10.1007/s11010-019-03654-0

M3 - Article

C2 - 31754972

AN - SCOPUS:85075302881

VL - 464

SP - 119

EP - 130

JO - Molecular and Cellular Biochemistry

JF - Molecular and Cellular Biochemistry

SN - 0300-8177

IS - 1-2

ER -