Natural Antioxidants Beneficial Effects on Anion Exchange through Band 3 Protein in Human Erythrocytes

Morabito, Rossana; Marino, Angela

doi:10.3390/antiox9010025

Cited by 30 publications

(32 citation statements)

References 55 publications

(80 reference statements)

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“…The SDS-PAGE analysis revealed that cell treatment with HgCl 2 results in alterations in the membrane protein electrophoretic profile, particularly related to bands 3, 4.1 and 4.2. Band 3 protein (B3p) is the most abundant integral protein on the RBC membrane, endowed with specific anion exchange capabilities, being responsible for acid balance, ion distribution and gas exchange [ 52 , 53 ]. Furthermore, it is also involved in RBC mechanical and osmotic properties, such as maintenance of biconcave cell shape and deformability.…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, it is also involved in RBC mechanical and osmotic properties, such as maintenance of biconcave cell shape and deformability. In particular, B3p is involved in specific protein–protein interactions, by connecting plasma membrane to the underlying cytoskeleton, through SH groups of specific Cys residues [ 53 ]. In this respect, Cys-201 and/or Cys-317, located at the cytoplasmic domain of B3p, are critical for ankyrin binding [ 54 ].…”

Section: Discussionmentioning

confidence: 99%

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Novel Insights into Mercury Effects on Hemoglobin and Membrane Proteins in Human Erythrocytes

et al. 2020

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Mercury (Hg) is a global environmental pollutant that affects human and ecosystem health. With the aim of exploring the Hg-induced protein modifications, intact human erythrocytes were exposed to HgCl2 (1–60 µM) and cytosolic and membrane proteins were analyzed by SDS-PAGE and AU-PAGE. A spectrofluorimetric assay for quantification of Reactive Oxygen Species (ROS) generation was also performed. Hg2+ exposure induces alterations in the electrophoretic profile of cytosolic proteins with a significant decrease in the intensity of the hemoglobin monomer, associated with the appearance of a 64 kDa band, identified as a mercurized tetrameric form. This protein decreases with increasing HgCl2 concentrations and Hg-induced ROS formation. Moreover, it appears resistant to urea denaturation and it is only partially dissociated by exposure to dithiothreitol, likely due to additional protein–Hg interactions involved in aggregate formation. In addition, specific membrane proteins, including band 3 and cytoskeletal proteins 4.1 and 4.2, are affected by Hg2+-treatment. The findings reported provide new insights into the Hg-induced possible detrimental effects on erythrocyte physiology, mainly related to alterations in the oxygen binding capacity of hemoglobin as well as decreases in band 3-mediated anion exchange. Finally, modifications of cytoskeletal proteins 4.1 and 4.2 could contribute to the previously reported alteration in cell morphology.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Novel Insights into Mercury Effects on Hemoglobin and Membrane Proteins in Human Erythrocytes

et al. 2020

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“…Human erythrocytes are continuously exposed to oxidative molecules transported within the vascular system and possibly interacting with erythrocytes membrane, and are more susceptible to oxidative stress than other cells [ 26 ]. Oxidative damage has been demonstrated to decrease survival and rheological properties of human erythrocytes, affecting their homeostasis, which is strictly linked to Band 3 protein (B3p) function [ 27 , 28 ].…”

Section: Introductionmentioning

confidence: 99%

d-Galactose Decreases Anion Exchange Capability through Band 3 Protein in Human Erythrocytes

et al. 2020

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d-Galactose (d-Gal), when abnormally accumulated in the plasma, results in oxidative stress production, and may alter the homeostasis of erythrocytes, which are particularly exposed to oxidants driven by the blood stream. In the present investigation, the effect of d-Gal (0.1 and 10 mM, for 3 and 24 h incubation), known to induce oxidative stress, has been assayed on human erythrocytes by determining the rate constant of SO42− uptake through the anion exchanger Band 3 protein (B3p), essential to erythrocytes homeostasis. Moreover, lipid peroxidation, membrane sulfhydryl groups oxidation, glycated hemoglobin (% A1c), methemoglobin levels (% MetHb), and expression levels of B3p have been verified. Our results show that d-Gal reduces anion exchange capability of B3p, involving neither lipid peroxidation, nor oxidation of sulfhydryl membrane groups, nor MetHb formation, nor altered expression levels of B3p. d-Gal-induced %A1c, known to crosslink with B3p, could be responsible for rate of anion exchange alteration. The present findings confirm that erythrocytes are a suitable model to study the impact of high sugar concentrations on cell homeostasis; show the first in vitro effect of d-Gal on B3p, contributing to the understanding of mechanisms underlying an in vitro model of aging; demonstrate that the first impact of d-Gal on B3p is mediated by early Hb glycation, rather than by oxidative stress, which may be involved on a later stage, possibly adding more knowledge about the consequences of d-Gal accumulation.

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“…We have previously shown that Syk overactivation favors band 3 clusterization, allowing the release of erythroid microparticles and red cell membrane rearrangement. In addition, oxidation might also affect band 3 function as an anion exchanger [ 27 , 44 , 45 ]. Exogenous antioxidants, such as curcumin or melatonin, as well as the potentiation of endogenous cytoprotectors like PEP-Prx2, might prevent or limit band 3 oxidative damage, preserving band 3 structure and function [ 17 , 44 , 45 ].…”

Section: Discussionmentioning

confidence: 99%

Tyrosine Phosphorylation Modulates Peroxiredoxin-2 Activity in Normal and Diseased Red Cells

et al. 2021

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Peroxiredoxin-2 (Prx2) is the third most abundant cytoplasmic protein in red blood cells. Prx2 belongs to a well-known family of antioxidants, the peroxiredoxins (Prxs), that are widely expressed in mammalian cells. Prx2 is a typical, homodimeric, 2-Cys Prx that uses two cysteine residues to accomplish the task of detoxifying a vast range of organic peroxides, H2O2, and peroxynitrite. Although progress has been made on functional characterization of Prx2, much still remains to be investigated on Prx2 post-translational changes. Here, we first show that Prx2 is Tyrosine (Tyr) phosphorylated by Syk in red cells exposed to oxidation induced by diamide. We identified Tyr-193 in both recombinant Prx2 and native Prx2 from red cells as a specific target of Syk. Bioinformatic analysis suggests that phosphorylation of Tyr-193 allows Prx2 conformational change that is more favorable for its peroxidase activity. Indeed, Syk-induced Tyr phosphorylation of Prx2 enhances in vitro Prx2 activity, but also contributes to Prx2 translocation to the membrane of red cells exposed to diamide. The biologic importance of Tyr-193 phospho-Prx2 is further supported by data on red cells from a mouse model of humanized sickle cell disease (SCD). SCD is globally distributed, hereditary red cell disorder, characterized by severe red cell oxidation due to the pathologic sickle hemoglobin. SCD red cells show Tyr-phosphorylated Prx2 bound to the membrane and increased Prx2 activity when compared to healthy erythrocytes. Collectively, our data highlight the novel link between redox related signaling and Prx2 function in normal and diseased red cells.

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Natural Antioxidants Beneficial Effects on Anion Exchange through Band 3 Protein in Human Erythrocytes

Cited by 30 publications

References 55 publications

Novel Insights into Mercury Effects on Hemoglobin and Membrane Proteins in Human Erythrocytes

Novel Insights into Mercury Effects on Hemoglobin and Membrane Proteins in Human Erythrocytes

d-Galactose Decreases Anion Exchange Capability through Band 3 Protein in Human Erythrocytes

Tyrosine Phosphorylation Modulates Peroxiredoxin-2 Activity in Normal and Diseased Red Cells

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