Human erythrocytes: cytoskeleton and its origin

Nigra, Ayelén D.; Casale, César H.; Santander, Verónica S.

doi:10.1007/s00018-019-03346-4

Cited by 26 publications

(35 citation statements)

References 127 publications

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“…Accordingly, their derivatization with thiol reagents are reported to block ankyrin interaction and a specific antibody raised against a synthetic peptide containing Cys-201 acts as a potent inhibitor of ankyrin binding [ 55 ]. Moreover, band 4.1 and 4.2 proteins, key components of the cytoskeleton network [ 56 ], also contain accessible cysteines [ 57 , 58 ]. In conclusion, a large body of literature, accumulated over several years by our group and others, clearly demonstrates the RBC structural and metabolic alterations induced by Hg, indicating severe alterations in the physiology and morphology of these cells.…”

Section: Discussionmentioning

confidence: 99%

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%

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

et al. 2020

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“…It is well known that blood cells grow in suspension, and the process of erythropoiesis is accompanied by great changes in cell morphology. The cell size gradually increases as hematopoietic progenitor cells (HPCs) differentiate into precursors (7), and then decreases during erythroblast maturation accompanied by cytoskeleton remodeling and loss of cytoplasmicnuclear connections (7,8). Moreover, some studies have revealed that the self-renewal and differentiation of HSCs are affected by cell morphology and adhesion.…”

Section: Introductionmentioning

confidence: 99%

RNA-seq reveals tight junction-relevant erythropoietic fate induced by OCT4 in human hair follicle mesenchymal stem cells

Sun

Huang

et al. 2020

Preprint

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Background: Human hair follicle mesenchymal stem cells (hHFMSCs) isolated from hair follicles possess multilineage differentiation potential. OCT4 is a gene critically associated with pluripotency properties. The cell morphology and adhesion of hHFMSCs significantly changed after transduction of OCT4 and two subpopulations emerged, including adherent cells and floating cell. Floating cells cultured in hematopoietic induction medium and stimulated with erythropoetic growth factors could transdifferentiate into mature erythrocytes, whereas adherent cells formed negligible hematopoietic colonies. The aim of this study was to reveal the role of cell morphology and adhesion on erythropoiesis induced by OCT4 in hHFMSCs and to characterize the molecular mechanisms involved.Methods: Floating cell were separated from adherent cell by centrifugation of the upper medium during cell culture. Cell size was observed through flow cytometry and cell adhesion was tested by disassociation and adhesion assays. RNA sequencing was performed to detect genome-wide transcriptomes and identify differentially expressed genes. GO enrichment analysis and KEGG pathway analysis were performed to analysis the functions and pathways enriched by differentially expressed genes. The expression of tight junction core members was verified by qPCR and Western blot. A regulatory network was constructed to figure out the relationship between cell adhesin, cytoskeleton, pluripotency and hematopoiesis.Results: The overexpression of OCT4 influenced the morphology and adhesion of hHFMSCs. Transcripts in floating cells and adherent cells are quite different. Data analysis showed that upregulated genes in floating cells were mainly related to pluripotency, germ layer development (including hematopoiesis lineage development), and downregulated genes were mainly related to cell adhesion, cell junctions and the cytoskeleton. Most molecules of the tight junction (TJ) pathway were downregulated and molecular homeostasis of the TJ was disturbed, as CLDNs were disrupted, and JAMs and TJPs were upregulated. The dynamic expression of cell adhesion-related gene E-cadherin and cytoskeleton-related gene ACTN2 might cause different morphology and adhesion. Finally, a regulatory network centered to OCT4 was constructed, which elucidated that he TJ pathway critically bridges pluripotency and hematopoiesis in a TJP1-dependent way.Conclusions: Regulations of cell morphology and adhesion via the TJ pathway conducted by OCT4 might modulate hematopoiesis in hHFMSCs, thus developing potential mechanism of erythropoiesis in vitro.

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“…Specialized tissue processing and fixation requirements for microtubule visualization precluded confirmatory studies on patient marrow samples. However, prior studies have shown that freshly obtained human peripheral red blood cells (RBC) retain remnant microtubule fragments that are disrupted by the microtubule destabilizer nocodazole [30][31][32][33] . IF for β-tubulin on RBC from non-anemic control patients confirmed the previously described pancellular stippling in the majority (>80%) of cells.…”

Section: Resultsmentioning

confidence: 99%

Iron control of erythroid microtubule cytoskeleton as a potential target in treatment of iron-restricted anemia

et al. 2021

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Anemias of chronic disease and inflammation (ACDI) result from restricted iron delivery to erythroid progenitors. The current studies reveal an organellar response in erythroid iron restriction consisting of disassembly of the microtubule cytoskeleton and associated Golgi disruption. Isocitrate supplementation, known to abrogate the erythroid iron restriction response, induces reassembly of microtubules and Golgi in iron deprived progenitors. Ferritin, based on proteomic profiles, regulation by iron and isocitrate, and putative interaction with microtubules, is assessed as a candidate mediator. Knockdown of ferritin heavy chain (FTH1) in iron replete progenitors induces microtubule collapse and erythropoietic blockade; conversely, enforced ferritin expression rescues erythroid differentiation under conditions of iron restriction. Fumarate, a known ferritin inducer, synergizes with isocitrate in reversing molecular and cellular defects of iron restriction and in oral remediation of murine anemia. These findings identify a cytoskeletal component of erythroid iron restriction and demonstrate potential for its therapeutic targeting in ACDI.

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Human erythrocytes: cytoskeleton and its origin

Cited by 26 publications

References 127 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

RNA-seq reveals tight junction-relevant erythropoietic fate induced by OCT4 in human hair follicle mesenchymal stem cells

Iron control of erythroid microtubule cytoskeleton as a potential target in treatment of iron-restricted anemia

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