Transglutaminase‐Mediated Remodeling of the Human Erythrocyte Membrane Skeleton: Relevance for Erythrocyte Diseases with Shortened Cell Lifespan

Lóránd, L.; Murthy, S. N. Prasanna; Khan, Anwar; Xue, Weilan; Lockridge, Oksana; Chishti, Athar H.

doi:10.1002/9781118105771.ch9

Cited by 3 publications

(5 citation statements)

References 54 publications

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“…As a result, in Ca 2+ overloaded RBCs formation of numerous polymeric protein complexes such as Glut1-adducin-dematin adducts as well as cross-linked complexes of Band 3-ankyrin-spectrin and glycophorin C -band 4.1-p55 occurs [85]. This Ca 2+ induced remodelling of the cytoskeletal structure and concomitant changes in cell shape and membrane plasticity are suggested to contribute to premature RBC clearance.…”

Section: Ca2+-sensitive Proteins In Rbcsmentioning

confidence: 99%

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Calcium in Red Blood Cells—A Perilous Balance

Bogdanova

Makhro

Wang

et al. 2013

IJMS

208

190

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Ca2+ is a universal signalling molecule involved in regulating cell cycle and fate, metabolism and structural integrity, motility and volume. Like other cells, red blood cells (RBCs) rely on Ca2+ dependent signalling during differentiation from precursor cells. Intracellular Ca2+ levels in the circulating human RBCs take part not only in controlling biophysical properties such as membrane composition, volume and rheological properties, but also physiological parameters such as metabolic activity, redox state and cell clearance. Extremely low basal permeability of the human RBC membrane to Ca2+ and a powerful Ca2+ pump maintains intracellular free Ca2+ levels between 30 and 60 nM, whereas blood plasma Ca2+ is approximately 1.8 mM. Thus, activation of Ca2+ uptake has an impressive impact on multiple processes in the cells rendering Ca2+ a master regulator in RBCs. Malfunction of Ca2+ transporters in human RBCs leads to excessive accumulation of Ca2+ within the cells. This is associated with a number of pathological states including sickle cell disease, thalassemia, phosphofructokinase deficiency and other forms of hereditary anaemia. Continuous progress in unravelling the molecular nature of Ca2+ transport pathways allows harnessing Ca2+ uptake, avoiding premature RBC clearance and thrombotic complications. This review summarizes our current knowledge of Ca2+ signalling in RBCs emphasizing the importance of this inorganic cation in RBC function and survival.

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Section: Ca2+-sensitive Proteins In Rbcsmentioning

confidence: 99%

“…Cross-linked polymers have been observed in RBCs of patients with SCD suggesting hyperactivation of transglutaminase [85]. …”

Section: Ca2+ Dysbalance and Haemolytic Anaemiamentioning

confidence: 99%

Calcium in Red Blood Cells—A Perilous Balance

Bogdanova

Makhro

Wang

et al. 2013

IJMS

208

190

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“…If Ca ++ accumulates, many harmful results occur, including activation of the protease calpain, activation of a K + efflux channel (the Gardos channel), inhibition of flippase/activation of scramblase, vesicle formation, transglutaminase activation [30], and decreased deformability. Ca ++ -dependent pathways are important for RBC in some disease states such as sickle cell disease and may contribute to RBC senescence [31].…”

Section: Biology Of Red Blood Cell Survivalmentioning

confidence: 99%

Measurement of Posttransfusion Red Cell Survival With the Biotin Label

Mock

Widness

Veng‐Pedersen

et al. 2014

Transfusion Medicine Reviews

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The goal of this review is to summarize and critically assess information concerning the biotin method to label red blood cells (RBC) for use in studies of RBC and transfusion biology — information that will prove useful to a broad audience of clinicians and scientists. A review of RBC biology, with emphasis on RBC senescence and in vivo survival is included, followed by an analysis of the advantages and disadvantages of biotin labeled RBC (BioRBC) for measuring circulating RBC volume, post-transfusion RBC recovery, RBC lifespan, and RBC age-dependent properties. The advantages of BioRBC over 51Cr RBC labeling, the current reference method, are discussed. Because the biotin method is straightforward and robust, including the ability to follow the entire lifespans of multiple RBC populations concurrently in the same subject, BioRBC offers distinct advantages for studying RBC biology and physiology, particularly RBC survival. The method for biotin labeling, validation of the method, and application of BioRBCs to studies of sickle cell disease, diabetes, and anemia of prematurity are reviewed. Studies documenting the safe use of BioRBC are reviewed; unanswered questions requiring future studies, remaining concerns, and regulatory barriers to broader application of BioRBC including adoption as a new reference method are also presented.

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“…Hemoglobin (Hb)-Köln disease is one of the hemoglobinopathies as a result of mutation of the b-globin of Hb and is characterized by changes in cell shape, increased density, and also by a loss of deformability. When cell membranes were isolated from erythrocytes of a patient with Hb-Köln disease (neither parent had the disease), the presence of high MW-crosslinked membrane structures, such as were found in the calcium-enriched model described above, was demonstrated (26). It is not difficult to conclude that the characteristic cell changes were caused by anything other than TG2-mediated formation of crosslinked supramolecular membrane proteins and that the resultant stiffening of the erythrocyte membrane by these polymers contributes to the extra-rapid clearing of erythrocytes from the circulation and hence, the shortened lifespan of Hb-Köln erythrocytes, from 120 to 31 d (26).…”

Section: The Human Erythrocyte Paradigm and Hemoglobin-köln Diseasementioning

confidence: 92%

“…Inasmuch as we currently do not have any means of hydrolyzing isopeptide crosslinks between proteins, detailed analysis of such large structures presents a formidable analytic problem. A modicum of success to identify the constituent molecules in such large crosslinked assemblies can be achieved by using immunoassays and mass spectrometry, both of which have their limitations (26).…”

Section: The Human Erythrocyte Paradigm and Hemoglobin-k öLn Diseasementioning

confidence: 99%

Transglutaminase diseases: from biochemistry to the bedside

Lóránd

Iismaa

2018

The FASEB Journal

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In humans, 9 members of the transglutaminase (TG) family have been identified, of which 8 [factor XIII (FXIII)A and TG1–TG7] catalyze post‐translational protein‐modifying reactions, and 1 does not (protein 4.2). The TG enzymatic activities considered in our discussion of human disease include deamidation of glutamine (Gln) residues, amine incorporation into Gln residues, and protein crosslinking. Except for TG7, which remains poorly studied, all individual TG members have been correlated with disparate human diseases that arise from either TG function or lack of function. Loss of TG function is associated with numerous orphan diseases that affect a relatively small number of individuals: loss of FXIIIa (transamidase‐activated form) crosslinking leads to defects in blood coagulation in FXIII deficiency; loss of TG1 and TG5 cross linking leads to defects in epidermal cornification in lamellar ichthyosis and acral peeling skin syndrome, respectively; loss of TG3 crosslinking in hair‐cuticle formation leads to uncombable hair syndrome; the predicted loss of TG6 crosslinking leads to spinocerebellar ataxia‐35; and loss of the structural erythrocyte membrane protein, protein 4.2, leads to hereditary spherocytosis type 5. The enzymatic activity of TG2 is involved in the exacerbation of celiac disease and in at least 1 case of hemoglobinopathy, characterized by shortened erythrocyte lifespan. TGs are also autoantigens in a number of immune diseases, resulting in the production of autoantibodies against FXIIIa in acquired FXIII deficiency, TG2 in celiac disease, TG3 in dermatitis herpetiformis, TG4 in autoimmume polyglandular syndrome type 1, and TG6 in gluten axonal neuropathy and gluten ataxia. Much still remains to be learned and confirmed with respect to disease mechanisms, particularly with respect to TG‐related immune diseases, in which development of isozyme‐specific inhibitors may be useful for treatment.—Lorand, L., Iismaa, S. E. Transglutaminase diseases: from biochemistry to the bedside. FASEB J. 33, 3–12 (2019). http://www.fasebj.org

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Transglutaminase‐Mediated Remodeling of the Human Erythrocyte Membrane Skeleton: Relevance for Erythrocyte Diseases with Shortened Cell Lifespan

Cited by 3 publications

References 54 publications

Calcium in Red Blood Cells—A Perilous Balance

Calcium in Red Blood Cells—A Perilous Balance

Measurement of Posttransfusion Red Cell Survival With the Biotin Label

Transglutaminase diseases: from biochemistry to the bedside

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