The Role of Calcium Metabolism in Human Red Blood Cell Ageing: A Proposal

Romero, Pedro; Romero, Eneida A.

doi:10.1006/bcmd.1999.0222

Cited by 48 publications

(31 citation statements)

References 26 publications

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“…The former, in particular, is known to play a pivotal role in the process of exocytosis, as it mediates vesicle docking to the membrane also, but not uniquely, in a calcium-dependent manner. 33 Since internal Ca 2+ is subjected to metabolic control via an ATP-dependent extrusion mechanism (Ca 2+ pump), 33,34 the decreased ATP content occurring during red cell aging should lead to a raised cellular Ca 2+ . This has been reported in the literature from studies that used the fluorescent probe Fura-2 in cells separated on Percoll density gradients, which revealed that in vivo aged RBC (senescent) contained a higher content of free Ca 2+ (almost four times higher) than the younger cells.…”

Section: Alterations Of Red Blood Cell Membrane Shape and Vesiculatiomentioning

confidence: 99%

Time-course investigation of SAGM-stored leukocyte-filtered red bood cell concentrates: from metabolism to proteomics

D’Alessandro¹,

D’Amici²,

Vaglio³

et al. 2011

Haematologica

184

209

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The online version of this article has a Supplementary Appendix. BackgroundResults from recent, highly debated, retrospective studies raised concerns and prompted considerations about further testing the quality of long stored red blood cells from a biochemical standpoint. Design and MethodsWe performed an integrated mass spectrometry-based metabolomics and proteomics timecourse investigation on SAGM-stored red blood cells. In parallel, structural changes during storage were monitored through scanning electron microscopy. ResultsWe detected increased levels of glycolytic metabolites over the first 2 weeks of storage. From day 14 onwards, we observed a significant consumption of all metabolic species, and diversion towards the oxidative phase of the pentose phosphate pathway. These phenomena coincided with the accumulation of reactive oxygen species and markers of oxidation (protein carbonylation and malondialdehyde accumulation) up to day 28. Proteomics evidenced changes at the membrane protein level from day 14 onwards. Changes included fragmentation of membrane structural proteins (spectrin, band 3, band 4.1), membrane accumulation of hemoglobin, antioxidant enzymes (peroxiredoxin-2) and chaperones. While the integrity of red blood cells did not show major deviations at day 14, at day 21 scanning electron microscope images revealed that 50% of the erythrocytes had severely altered shape. We could correlate the scanning electron microscopy observations with the onset of vesiculation, through a proteomics snapshot of the difference in the membrane proteome at day 0 and day 35. We detected proteins involved in vesicle formation and docking to the membrane, such as SNAP alpha. ConclusionsBiochemical and structural parameters did not show significant alterations in the first 2 weeks of storage, but then declined constantly from day 14 onwards. We highlighted several parallelisms between red blood cells stored for a long time and the red blood cells of patients with hereditary spherocytosis.Key words: red blood cell, storage, mass spectrometry, proteomics, metabolomics. Haematologica 2012;97(1):107-115. doi:10.3324/haematol.2011 Citation: D'Alessandro A, D'Amici GM, Vaglio S, and Zolla L. Time-course investigation of SAGM-stored leukocyte-filtered red blood cell concentrates: from metabolism to proteomics.

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Section: Alterations Of Red Blood Cell Membrane Shape and Vesiculatiomentioning

confidence: 99%

Time-course investigation of SAGM-stored leukocyte-filtered red bood cell concentrates: from metabolism to proteomics

D’Alessandro¹,

D’Amici²,

Vaglio³

et al. 2011

Haematologica

184

209

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“…Age-dependent elevation of cytosolic Ca 2+ followed by activation of the Gardos channel, scramblase and calpain (Fig 5) was proposed as a mechanism responsible for the triggering of programmed cell death and removal of dying erythrocytes from circulation [183]. Erythrocyte ageing is accompanied by an increase in the activity of mechano-sensitive Ca 2+ -permeable cation channels [90] and by decrease in the activity of the Ca 2+ pump [184].…”

Section: +mentioning

confidence: 99%

Erythrocyte Signal Transduction Pathways, their Oxygenation Dependence and Functional Significance

Barvitenko

Adragna

Weber³

2005

Cell Physiol Biochem

135

104

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Erythrocytes play a key role in human and vertebrate metabolism. Tissue O₂ supply is regulated by both hemoglobin (Hb)-O₂ affinity and erythrocyte rheology, a key determinant of tissue perfusion. Oxygenation-deoxygenation transitions of Hb may lead to re-organization of the cytoskeleton and signalling pathways activation/deactivation in an O₂-dependent manner. Deoxygenated Hb binds to the cytoplasmic domain of the anion exchanger band 3, which is anchored to the cytoskeleton, and is considered a major mechanism underlying the oxygenation-dependence of several erythrocyte functions. This work discusses the multiple modes of Hb-cytoskeleton interactions. In addition, it reviews the effects of Mg²⁺, 2,3-diphosphoglycerate, NO, shear stress and Ca²⁺, all factors accompanying the oxygenation-deoxygenation cycle in circulating red cells. Due to the extensive literature on the subject, the data discussed here, pertain mainly to human erythrocytes whose O₂ affinity is modulated by 2,3-diphosphoglycerate, ectothermic vertebrate erythrocytes that use ATP, and to bird erythrocytes that use inositol pentaphosphate.

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“…Elevated [Ca 2ϩ ] i has also been implicated in the activation of cell proteases and in the cross-linking of cytoskeletal proteins, with cumulative effects on cell aging and viability. [11][12][13][14][15] The first indirect evidence of substantial cell-to-cell variations in PMCA V max arose when Tiffert et al 16 examined the dehydration response of RBCs uniformly permeabilized to Ca 2ϩ with the ionophore A23187. As Ca 2ϩ influx into RBCs was progressively increased by increasing the ionophore concentration in a stepwise manner, RBCs suspended in plasmalike media dehydrated following an all-or-none rather than a graded pattern: Instead of all cells dehydrating at progressively faster rates-as expected with a uniform response-only a fraction of RBCs dehydrated and this fraction increased with increasing Ca 2ϩ influx.…”

Section: Introductionmentioning

confidence: 99%

Distribution of plasma membrane Ca2+ pump activity in normal human red blood cells

Lew

Daw

Perdomo

et al. 2003

Blood

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IntroductionThe plasma membrane Ca 2ϩ pump (PMCA), in its various isoforms, is expressed in all animal cells, where it plays a major role in the control of resting intracellular-free Ca 2ϩ levels ([Ca 2ϩ ] i ). [1][2][3][4] The PMCA was originally discovered and extensively studied in human red blood cells (RBCs) in which it is the only active Ca 2ϩ extrusion transporter. The maximal Ca 2ϩ transport capacity (V max ) of the PMCA in human RBCs (approximately 10 mmol [340 g hemoglobin {Hb}] Ϫ1 h Ϫ1 ) is high compared with the normal pump-leak turnover rate of Ca 2ϩ (approximately 50 mol [340 g Hb] Ϫ1 h Ϫ1 ). 3 Although early work indicated that Ca 2ϩ pump activity may vary from cell to cell over a much broader range than any other known hematologic parameter, 5 available measurements of PMCA V max in intact RBCs always reported mean values in the RBC population 6 ; the actual distribution of PMCA V max activity among RBCs was unknown. The aim of the present work was to characterize the distribution of PMCA V max activity in normal human RBCs.It is important to ascertain the extent of PMCA V max variation among RBCs because differences in pump-leak [Ca 2ϩ ] i levels may determine the degree of vulnerability of individual cells to certain physiologic and pathologic stresses. Human RBCs express in their plasma membrane a Ca 2ϩ -sensitive K ϩ channel (the "Gardos" channel 7-9 ). Hoffman et al 10 recently showed that the isoform hSK4 represents the small conductance Gardos channel of human RBCs. In conditions with elevated [Ca 2ϩ ] i , Gardos channel activation causes rapid net loss of KCl and water, leading to irreversible cell dehydration. Elevated [Ca 2ϩ ] i has also been implicated in the activation of cell proteases and in the cross-linking of cytoskeletal proteins, with cumulative effects on cell aging and viability. [11][12][13][14][15] The first indirect evidence of substantial cell-to-cell variations in PMCA V max arose when Tiffert et al 16 examined the dehydration response of RBCs uniformly permeabilized to Ca 2ϩ with the ionophore A23187. As Ca 2ϩ influx into RBCs was progressively increased by increasing the ionophore concentration in a stepwise manner, RBCs suspended in plasmalike media dehydrated following an all-or-none rather than a graded pattern: Instead of all cells dehydrating at progressively faster rates-as expected with a uniform response-only a fraction of RBCs dehydrated and this fraction increased with increasing Ca 2ϩ influx. Further experiments showed that Gardos channel activity among the RBCs was fairly uniform and could not have accounted for this all-or-none pattern. 17 These results suggested that uniform Ca 2ϩ permeabilization of RBCs did not generate uniformly elevated [Ca 2ϩ ] i among the cells and that the differences arose from variations in Ca 2ϩ pump activity.Further evidence for marked variations in Ca 2ϩ pump activity among RBCs from single donors was provided by 19 who detected large differences in the total Ca 2ϩ content of RBCs ([Ca T ] i ) uniformly permeabilized to ...

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The Role of Calcium Metabolism in Human Red Blood Cell Ageing: A Proposal

Cited by 48 publications

References 26 publications

Time-course investigation of SAGM-stored leukocyte-filtered red bood cell concentrates: from metabolism to proteomics

Time-course investigation of SAGM-stored leukocyte-filtered red bood cell concentrates: from metabolism to proteomics

Erythrocyte Signal Transduction Pathways, their Oxygenation Dependence and Functional Significance

Distribution of plasma membrane Ca2+ pump activity in normal human red blood cells

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