Effect of Mercury on Membrane Proteins, Anionic Transport and Cell Morphology in Human Erythrocytes.

Détails

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Etat: Public
Version: Final published version
Licence: CC BY-NC-ND 4.0
ID Serval
serval:BIB_1C35A85AD818
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Effect of Mercury on Membrane Proteins, Anionic Transport and Cell Morphology in Human Erythrocytes.
Périodique
Cellular physiology and biochemistry
Auteur⸱e⸱s
Notariale R., Längst E., Perrone P., Crettaz D., Prudent M., Manna C.
ISSN
1421-9778 (Electronic)
ISSN-L
1015-8987
Statut éditorial
Publié
Date de publication
21/09/2022
Peer-reviewed
Oui
Volume
56
Numéro
5
Pages
500-513
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: ppublish
Résumé
Mercury (Hg) is a heavy metal widespread in all environmental compartments as one of the most hazardous pollutants. Human exposure to this natural element is detrimental for several cellular types including erythrocytes (RBC) that accumulate Hg mainly bound to the SH groups of different cellular components, including protein cysteine residues. The cellular membrane represents a major target of Hg-induced damage in RBC with loss of physiological phospholipid asymmetry, due to phosphatidylserine (PS) exposure to the external membrane leaflet. To investigate Hg-induced cytotoxicity at the molecular level, the possible interaction of this heavy metal with RBC membrane proteins was investigated. Furthermore, Hg-induced alterations in band 3 protein (B3p) transport function, PS-exposing macrovesicle (MVs) formation and morphological changes were assessed.
For this aim, human RBC were treated in vitro with different HgCl <sub>2</sub> concentrations (range 10-40 µM) and the electrophoretic profile of membrane proteins as well as the expression levels of Ankyrin and Flottilin-2 evaluated by SDS-PAGE and Western blot, respectively. The effect of alterations in these proteins on RBC morphology was evaluated by digital holographic microscopy and anionic transport efficiency of B3p was evaluated as sulphate uptake. Finally, PS- bearing MVs were quantified by annexin-V binding using FACS analysis.
Findings presented in this paper indicate that RBC exposure to HgCl <sub>2</sub> induces modifications in the electrophoretic profile of membrane protein fraction. Furthermore, our study reveals the Hg induced alterations of specific membrane proteins, such as Ankyrin, a protein essential for membrane-cytoskeleton linkage and Flotillin-2, a major integral protein of RBC lipid rafts, likely responsible for decreased membrane stability and increased fragmentations. Accordingly, under the same experimental conditions, RBC morphological changes and PS-bearing MVs release are observed. Finally, RBC treatment significantly affects the B3p-mediated anionic transport, that we report reduced upon HgCl <sub>2</sub> treatment in a dose dependent manner.
Altogether, the findings reported in this paper confirm that RBC are particularly vulnerable to Hg toxic effect and provide new insight in the Hg-induced protein modification in human RBC affecting the complex biological system of cellular membrane. In particular, Hg could induce dismantle of vertical cohesion between the plasma membrane and cytoskeleton as well as destabilization of lateral linkages of functional domains. Consequently, decreased membrane deformability could impair RBC capacity to deal with the shear forces in the circulation increasing membrane fragmentations. Furthermore, findings described in this paper have also significant implication in RBC physiology, particularly related to gas exchanges.
Mots-clé
Anion Exchange Protein 1, Erythrocyte/metabolism, Ankyrins/metabolism, Ankyrins/pharmacology, Annexin A5/metabolism, Cysteine/metabolism, Environmental Pollutants, Erythrocytes/metabolism, Humans, Membrane Proteins/metabolism, Mercury/metabolism, Mercury/toxicity, Phosphatidylserines/metabolism, Phospholipids/metabolism, Sulfates/metabolism, Ankyrin; Anionic transport; Erythrocytes; Flotillin-2; Mercury
Pubmed
Open Access
Oui
Création de la notice
27/09/2022 14:30
Dernière modification de la notice
21/11/2022 8:23
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