In silico modeling and metabolome analysis of long-stored erythrocytes to improve blood storage methods

Nishino, Taiko; Yachie‐Kinoshita, Ayako; Hirayama, Akiyoshi; Soga, Tomoyoshi; Suematsu, Makoto; Tomita, Masaru

doi:10.1016/j.jbiotec.2009.08.010

Cited by 43 publications

(63 citation statements)

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“…Diphosphoglycerate (DPG) levels followed trends already reported in literature, 11,20 with early moderate accumulation up to day 7 and then a constant decrease until day 21 and onwards, at which point the concentrations were as low as 0.05±0.01% of the original day 0 values.…”

Section: Time-course Metabolomicssupporting

confidence: 67%

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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

183

205

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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: Time-course Metabolomicssupporting

confidence: 67%

“…Lactate, which is a frequently measured parameter in metabolic analyses of RBC, 11,20 , constantly accumulated as storage progressed, reaching a final 20.39±0.9 fold increase in comparison to day 0 control levels.…”

Section: Time-course Metabolomicsmentioning

confidence: 94%

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

183

205

View full text Add to dashboard Cite

show abstract

“…In a previous study, Nishino et al developed a mathematical model for erythrocytes and used it to predict metabolic changes occurring during their long-term storage. In silico simulations reproduced the reported time-courses of ATP and 2.3-DPG during storage and these predictions were validated by comparison with metabolomics data [21].…”

Section: Systems Biology Of Stored Blood Cellsmentioning

confidence: 58%

Systems biology of stored blood cells: Can it help to extend the expiration date?

Paglia

Palsson

Sigurjónsson

2012

Journal of Proteomics

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“…There are very few reports providing comprehensive measurements of metabolites present in the RBCs 17 and no reports on global metabolites changes associated with SCD. The aim of this study was to develop a simple and comprehensive strategy for metabolite extraction and metabolome analysis of purified human RBCs from normal person and sickle cell-affected patients and also to determine pathways that might be of interest to prevent vaso-occlusion and to monitor the effects of new drugs on SCD.…”

Section: Introductionmentioning

confidence: 99%

Pathophysiology of sickle cell disease is mirrored by the red blood cell metabolome

Darghouth

Koehl

Madalinski³

et al. 2011

Blood

103

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Emerging metabolomic tools can now be used to establish metabolic signatures of specialized circulating hematopoietic cells in physiologic or pathologic conditions and in human hematologic diseases. To determine metabolomes of normal and sickle cell erythrocytes, we used an extraction method of erythrocytes metabolites coupled with a liquid chromatography-mass spectrometrybased metabolite profiling method. Comparison of these 2 metabolomes identified major changes in metabolites produced by (1) endogenous glycolysis characterized by accumulation of many glycolytic intermediates; (2) endogenous glutathione and ascorbate metabolisms characterized by accumulation of ascorbate metabolism intermediates, such as diketogulonic acid and decreased levels of both glutathione and glutathione disulfide; (3) membrane turnover, such as carnitine, or membrane transport characteristics, such as amino acids; and (4) exogenous arginine and NO metabolisms, such as spermine, spermidine, or citrulline. Finally, metabolomic analysis of young and old normal red blood cells indicates metabolites whose levels are directly related to sickle cell disease. These results show the relevance of metabolic profiling for the follow-up of sickle cell patients or other red blood cell diseases and pinpoint the importance of metabolomics to further depict the pathophysiology of human hematologic diseases. (Blood. 2011; 117(6):e57-e66) IntroductionMetabolome is defined as the complete set of metabolites present in a given biologic system that can be unicellular organism, organ, tissue, cell, or biologically relevant liquid compartments. Complementary to genomics or proteomics, the aim of metabolome analysis is to describe qualitatively and quantitatively the final products of cellular regulatory pathways and can be seen as the ultimate response of a biologic system to genetic factors and/or environmental changes. 1 Presently, metabolomics is used to describe metabolites present in simple unicellular organisms, such as Escherichia coli, 2 or in important biologic fluids, such as plasma or urine, 3,4 but the cross-talks between cells in tissues or the complex metabolism in mammalian cells make the interpretation of metabolomics data challenging in human, although important metabolites involved in pathogenesis of cancer, 5,6 diabetes, 7 and cardiovascular 8,9 and mitochondrial diseases 10 are described.Mammalian mature red blood cell (RBC) is a cell without nucleus or cytoplasmic organelles, such as mitochondria or ribosomes, easy to collect and to purify in large quantity. In human, during their 120-day life span, RBCs are perfectly adapted to oxygen, carbon dioxide, and proton transport. RBCs have also an important role in interorgan transport of metabolites, such as amino acid transport to muscles resulting from numerous amino acids receptors on RBC membranes. RBCs are also used as reporters of exogenous metabolisms as exemplified by the level of hemoglobin A1c, which is a measure of erythrocyte hemoglobin glycation and reflects mean glycemia for the...

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In silico modeling and metabolome analysis of long-stored erythrocytes to improve blood storage methods

Cited by 43 publications

References 50 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

Systems biology of stored blood cells: Can it help to extend the expiration date?

Pathophysiology of sickle cell disease is mirrored by the red blood cell metabolome

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