Genome-wide metabolite quantitative trait loci analysis (mQTL) in red blood cells from volunteer blood donors

Moore, Amy; Busch, Michael P.; Dziewulska, Karolina; Francis, Richard O.; Hod, Eldad A.; Zimring, James C.; D’Alessandro, Angelo; Page, Grier P.

doi:10.1016/j.jbc.2022.102706

Cited by 16 publications

(19 citation statements)

References 80 publications

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“…Recent studies have shown “heritability” in some erythrocytic features during storage. Genome-wide association studies (GWAS) identified several loci associated with hemolysis ( Page et al, 2021 ; Fang et al, 2022 ) or metabolism ( Moore et al, 2022 ) of stored RBCs, and similar conclusions also arose from classic twin studies ( van 't Erve et al, 2014a ; van 't Erve et al, 2014b ). Correlation analyses support these findings ( Reisz et al, 2017 ; Tzounakas et al, 2021 ), and enrich them with inter-correlations, namely, correlations between distinct parameters, either before/during storage, or between different time points of storage ( D'Alessandro et al, 2021 ; Thomas et al, 2021 ; Anastasiadi et al, 2022 ).…”

Section: Introductionmentioning

confidence: 65%

“…Such information provides the ability to monitor proportional changes in purine oxidation molecules with the potential to undermine post-transfusion RBC performance such as inosine and hypoxanthine ( D'Alessandro et al, 2017a ; Nemkov et al, 2018 ), while the inverse correlation between allantoate and xanthosine seems to support our previous hypothesis, that under these conditions, UA acts on xanthosine rather than on classic stress-biomarkers (hypoxanthine, allantoin) ( Kand’ar and Zakova, 2008 ; Nemkov et al, 2018 ). Regarding heritability in purines, the storage levels of urate have been linked to the gene of folate receptor ( Moore et al, 2022 ), a finding that seems to match the observed alteration of folate metabolites in UA-supplementations ( Tzounakas et al, 2022 ).…”

Section: Discussionmentioning

confidence: 89%

“…Therefore, the new environment, which is dissimilar to the in vivo in terms of redox equilibrium, might be bringing this specific donor-signature to the surface. Interestingly, a recent GWAS revealed a panel of metabolites strongly associated to the variation in genes implicated to RBC redox status, including the repair of oxidatively-damaged lipids ( Moore et al, 2022 ). The fact that the extracellular antioxidant capacity −previously shown to be proportional to the pre-storage levels ( Reisz et al, 2017 )− failed to maintain the correlation pattern in the mix-treatments, might be attributed to the excessive enhancement, which led to a “burnout” effect when both antioxidants were added ( Tzounakas et al, 2022 ).…”

Section: Discussionmentioning

confidence: 99%

“…Regarding metabolic aspects, classic twin studies and GWAS have shown a genetic control of glycolysis and PPP in stored RBCs ( van 't Erve et al, 2014b ; Weisenhorn et al, 2016 ; Moore et al, 2022 ). In our cohort, this donor-signature is lost between the time points of storage in the untreated units.…”

Section: Discussionmentioning

confidence: 99%

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The time-course linkage between hemolysis, redox, and metabolic parameters during red blood cell storage with or without uric acid and ascorbic acid supplementation

Anastasiadi

Stamoulis²,

Papageorgiou

et al. 2023

Front. Aging

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Oxidative phenomena are considered to lie at the root of the accelerated senescence observed in red blood cells (RBCs) stored under standard blood bank conditions. It was recently shown that the addition of uric (UA) and/or ascorbic acid (AA) to the preservative medium beneficially impacts the storability features of RBCs related to the handling of pro-oxidant triggers. This study constitutes the next step, aiming to examine the links between hemolysis, redox, and metabolic parameters in control and supplemented RBC units of different storage times. For this purpose, a paired correlation analysis of physiological and metabolism parameters was performed between early, middle, and late storage in each subgroup. Strong and repeated correlations were observed throughout storage in most hemolysis parameters, as well as in reactive oxygen species (ROS) and lipid peroxidation, suggesting that these features constitute donor-signatures, unaffected by the diverse storage solutions. Moreover, during storage, a general “dialogue” was observed between parameters of the same category (e.g., cell fragilities and hemolysis or lipid peroxidation and ROS), highlighting their interdependence. In all groups, extracellular antioxidant capacity, proteasomal activity, and glutathione precursors of preceding time points anticorrelated with oxidative stress lesions of upcoming ones. In the case of supplemented units, factors responsible for glutathione synthesis varied proportionally to the levels of glutathione itself. The current findings support that UA and AA addition reroutes the metabolism to induce glutathione production, and additionally provide mechanistic insight and footing to examine novel storage optimization strategies.

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Section: Introductionmentioning

confidence: 65%

Section: Discussionmentioning

confidence: 89%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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The time-course linkage between hemolysis, redox, and metabolic parameters during red blood cell storage with or without uric acid and ascorbic acid supplementation

Anastasiadi

Stamoulis²,

Papageorgiou

et al. 2023

Front. Aging

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“…NADH is required both by lactate dehydrogenase to convert pyruvate to lactate and by cytochrome b5‐reductase to reduce methaemoglobin back to haemoglobin. During oxidative stress, such as in individuals with glucose‐6‐phosphate dehydrogenase deficiency, NADH is consumed by cytochrome b5‐reductase at faster rates leading to increased pyruvate‐to‐lactate ratio, 427,428 thereby, decreasing glycolytic flux. Finally, emerging evidence suggests the potential involvement of fatty acid desaturases, an NADH‐dependent system, in modulating erythrocyte metabolism 131 .…”

Section: The Dynamics Of Erythrocyte Metabolismmentioning

confidence: 99%

Erythrocyte metabolism

Chatzinikolaou,

Margaritelis,

Paschalis

et al. 2024

Acta Physiologica

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Our aim is to present an updated overview of the erythrocyte metabolism highlighting its richness and complexity. We have manually collected and connected the available biochemical pathways and integrated them into a functional metabolic map. The focus of this map is on the main biochemical pathways consisting of glycolysis, the pentose phosphate pathway, redox metabolism, oxygen metabolism, purine/nucleoside metabolism, and membrane transport. Other recently emerging pathways are also curated, like the methionine salvage pathway, the glyoxalase system, carnitine metabolism, and the lands cycle, as well as remnants of the carboxylic acid metabolism. An additional goal of this review is to present the dynamics of erythrocyte metabolism, providing key numbers used to perform basic quantitative analyses. By synthesizing experimental and computational data, we conclude that glycolysis, pentose phosphate pathway, and redox metabolism are the foundations of erythrocyte metabolism. Additionally, the erythrocyte can sense oxygen levels and oxidative stress adjusting its mechanics, metabolism, and function. In conclusion, fine‐tuning of erythrocyte metabolism controls one of the most important biological processes, that is, oxygen loading, transport, and delivery.

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Unearthing FLVCR1a: tracing the path to a vital cellular transporter

Fiorito,

Tolosano

2024

Cell. Mol. Life Sci.

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The Feline Leukemia Virus Subgroup C Receptor 1a (FLVCR1a) is a member of the SLC49 Major Facilitator Superfamily of transporters. Initially recognized as the receptor for the retrovirus responsible of pure red cell aplasia in cats, nearly two decades since its discovery, FLVCR1a remains a puzzling transporter, with ongoing discussions regarding what it transports and how its expression is regulated. Nonetheless, despite this, the substantial body of evidence accumulated over the years has provided insights into several critical processes in which this transporter plays a complex role, and the health implications stemming from its malfunction. The present review intends to offer a comprehensive overview and a critical analysis of the existing literature on FLVCR1a, with the goal of emphasising the vital importance of this transporter for the organism and elucidating the interconnections among the various functions attributed to this transporter.

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Genome-wide metabolite quantitative trait loci analysis (mQTL) in red blood cells from volunteer blood donors

Cited by 16 publications

References 80 publications

The time-course linkage between hemolysis, redox, and metabolic parameters during red blood cell storage with or without uric acid and ascorbic acid supplementation

The time-course linkage between hemolysis, redox, and metabolic parameters during red blood cell storage with or without uric acid and ascorbic acid supplementation

Erythrocyte metabolism

Unearthing FLVCR1a: tracing the path to a vital cellular transporter

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