Mercury leads to abnormal red blood cell adhesion to laminin mediated by membrane sulfatides

Akkaya, Birnur; Kucukal, Erdem; Little, Jane A.; Gürkan, Umut A.

doi:10.1016/j.bbamem.2019.03.008

Cited by 14 publications

(7 citation statements)

References 67 publications

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“…Of particular interest are the data from Flotillin-2, a major protein of lipid raft that contributes the organization of functional domains [29,51,52]. Therefore, the effect of Hg treatment on this protein was analyzed by Western blot.…”

Section: Discussionmentioning

confidence: 99%

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

2022

Cell Physiol Biochem

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Background/Aims: 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. Methods: For this aim, human RBC were treated in vitro with different HgCl2 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. Results: Findings presented in this paper indicate that RBC exposure to HgCl2 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 HgCl2 treatment in a dose dependent manner. Conclusion: 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.

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Section: Discussionmentioning

confidence: 99%

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

2022

Cell Physiol Biochem

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“…The adhesion of RBCs was observed under physiological flow conditions. 59 The results showed that basal cell adhesion molecule and Lutheran (BCAM-Lu) chimeras significantly inhibited RBC adhesion during the first hour of exposure while sulfolipids did not play a role in this process. But after Hg 2+ treatment for more than one hour, BCAM-Lu chimeras had no significant effect on RBC adhesion.…”

Section: Microfluidics For Detection Of Cvd Markersmentioning

confidence: 94%

Microfluidics for diagnosis and treatment of cardiovascular disease

Liu

Cao

et al. 2023

J. Mater. Chem. B

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“…Fabrication of microfluidic chips was performed as previously described. [49][50][51][52] Briefly, a double-sided adhesive (DSA) polyester film was placed in between a top polymethyl methacrylate (PMMA) cover, and a bottom glass microscope slide pre-coated with 3-aminopropyl triethoxysilane (APTES, Gold Seal Electron Microscopy Sciences, Hatfield, PA). The DSA film and PMMA top cover were laser micro-machined to define the microchannel walls as well as inlet and outlet ports.…”

Section: Fabrication Of Microfluidic Assaysmentioning

confidence: 99%

Whole blood viscosity and red blood cell adhesion: Potential biomarkers for targeted and curative therapies in sickle cell disease

et al. 2020

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Sickle cell disease (SCD) is a recessive genetic blood disorder exhibiting abnormal blood rheology. Polymerization of sickle hemoglobin, due to a point mutation in the β-globin gene of hemoglobin, results in aberrantly adhesive and stiff red blood cells (RBCs). Hemolysis, abnormal RBC adhesion, and abnormal blood rheology together impair endothelial health in people with SCD, which leads to cumulative systemic complications. Here, we describe a microfluidic assay combined with a micro particle image velocimetry technique for the integrated in vitro assessment of whole blood viscosity (WBV) and RBC adhesion. We examined WBV and RBC adhesion to laminin (LN) in microscale flow in whole blood samples from 53 individuals with no hemoglobinopathies (HbAA, N = 10), hemoglobin SC disease (HbSC, N = 14), or homozygous SCD (HbSS, N = 29) with mean WBV of 4.50 cP, 4.08 cP, and 3.73 cP, respectively. We found that WBV correlated with RBC count and hematocrit in subjects with HbSC or HbSS. There was a significant inverse association between WBV and RBC adhesion under both normoxic and physiologically hypoxic (SpO 2 of 83%) tests, in which lower WBV associated with higher RBC adhesion to LN in subjects with HbSS. Low WBV has been found by others to associate with endothelial activation. Altered WBV and abnormal RBC adhesion may synergistically contribute to the endothelial damage and cumulative pathophysiology of SCD. These findings suggest that WBV and RBC adhesion may serve as clinically relevant biomarkers and endpoints in assessing emerging targeted and curative therapies in SCD. 1 | INTRODUCTION Sickle cell disease (SCD) is one of the most common inherited diseases in the world. 1,2 It is caused by a single-point mutation in the β-globin gene of hemoglobin. Sickle hemoglobin (HbS) polymerizes into long and stiff chains within the red blood cell (RBC) under low-oxygen conditions. 3,4 As a result, HbS-containing RBCs (sickle RBCs) become abnormally stiff and adherent (impairing microcirculatory blood flow), and fragile (resulting in hemolysis). Microvascular occlusion causes episodic and unpredictable vaso-occlusive events (VOE), pain, and Erdem Kucukal and Yuncheng Man contributed equally to this study.

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Mercury leads to abnormal red blood cell adhesion to laminin mediated by membrane sulfatides

Cited by 14 publications

References 67 publications

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

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

Microfluidics for diagnosis and treatment of cardiovascular disease

Whole blood viscosity and red blood cell adhesion: Potential biomarkers for targeted and curative therapies in sickle cell disease

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