Metabolic fate of adenine in red blood cells during storage in SAGM solution

Paglia, Giuseppe; Sigurjónsson, Ólafur E.; Bordbar, Aarash; Rolfsson, Óttar; Magnusdottir, Manuela; Palsson, Sirus; Wichuk, Kristine; Guðmundsson, Sveinn; Palsson, Bernhard Ø.

doi:10.1111/trf.13740

Cited by 35 publications

(35 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Second, additional markers were identified with methionine and sulfur metabolism (specifically S-adenosyl-methionine and S-adenosyl-homocysteine) emerging as significant variables informing storage time and additive solution-specific clustering. Although this and other studies have pointed out the potential relevance of storage-induced methionine consumption and activation of the trans-sulfuration pathway in relation to purine homeostasis and polyamine synthesis, 8,21,24 further studies will be necessary to mechanistically assess the relevance of this pathway.…”

Section: Discussionmentioning

confidence: 86%

“…supplementation with adenine, alternative sugars or antioxidants). 21–23 Tracing experiments have provided insights into fluxes through key antioxidant pathways 15 or previously unappreciated metabolic reactions in stored RBCs, such as those involving citrate and other carboxylates, 13,24 expanding our understanding of RBC biology in general. In addition, systems biology elaboration of metabolomics data has contributed a mathematical tool to identify three metabolic phases during routine storage, 25 which can be used to test and predict RBC storability in new storage additives in silico .…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Heterogeneity of blood processing and storage additives in different centers impacts stored red blood cell metabolism as much as storage time: lessons from REDS‐III—Omics

et al. 2018

View full text Add to dashboard Cite

Background Biological and technical variability has been increasingly appreciated as a key factor impacting red blood cell (RBC) storability and, potentially, transfusion outcomes. Here we performed metabolomics analyses to investigate the impact of factors other than storage duration on the metabolic phenotypes of stored RBC in a multi-center study. Study design and Methods Within the framework of the REDS-III RBC-Omics study, 13,403 donors were enrolled from four blood centers across the United States and tested for the propensity of their RBCs to hemolyze after 42 days of storage. Extreme hemolyzers were recalled and donated a second unit of blood. Units were stored for 10, 23 and 42 days prior to sample acquisition for metabolomics analyses. Results Unsupervised analyses of metabolomics data from 599 selected samples revealed a strong impact (14.2% of variance) of storage duration on metabolic phenotypes of RBCs. The blood center collecting and processing the units explained an additional 12.2% of the total variance, a difference primarily attributable to the storage additive (AS-1 vs AS-3) used in the different hubs. Samples stored in mannitol-free/citrate-loaded AS-3 were characterized by elevated levels of high-energy compounds, improved glycolysis and glutathione homeostasis. Increased methionine metabolism and activation of the trans-sulfuration pathway was noted in samples processed in the center using AS-1. Conclusion Blood processing impacts the metabolic heterogeneity of stored RBCs from the largest multi-center metabolomics study in transfusion medicine to date. Studies are needed to understand if these metabolic differences influenced by processing/storage strategies impact the effectiveness of transfusions clinically.

show abstract

Section: Discussionmentioning

confidence: 86%

Section: Introductionmentioning

confidence: 99%

Heterogeneity of blood processing and storage additives in different centers impacts stored red blood cell metabolism as much as storage time: lessons from REDS‐III—Omics

et al. 2018

View full text Add to dashboard Cite

show abstract

“…Plasma and RBCs account for more than 99% of the blood content, so it appears reasonable to detect RBC intracellular metabolites in the whole blood metabolome. Indeed, Europe PMC Funders Author Manuscripts in the extracted metabolome, we found several intracellular metabolites that are typically present in high amounts in the RBC metabolome, such as heme, AMP, IMP, glucose-6-phosphate, and fructose 6-phosphate [35][36][37]. Although these metabolites were extracted in all conditions (Fig.…”

Section: Europe Pmc Funders Author Manuscriptsmentioning

confidence: 98%

Pre-analytic evaluation of volumetric absorptive microsampling and integration in a mass spectrometry-based metabolomics workflow

et al. 2017

Self Cite

View full text Add to dashboard Cite

Volumetric absorptive microsampling (VAMS) is a novel approach that allows single-drop (10 μL) blood collection. Integration of VAMS with mass spectrometry (MS)-based untargeted metabolomics is an attractive solution for both human and animal studies. However, to boost the use of VAMS in metabolomics, key pre-analytical questions need to be addressed. Therefore, in this work, we integrated VAMS in a MS-based untargeted metabolomics workflow and investigated pre-analytical strategies such as sample extraction procedures and metabolome stability at different storage conditions. We first evaluated the best extraction procedure for the polar metabolome and found that the highest number and amount of metabolites were recovered upon extraction with acetonitrile/water (70:30). In contrast, basic conditions (pH 9) resulted in divergent metabolite profiles mainly resulting from the extraction of intracellular metabolites originating from red blood cells. In addition, the prolonged storage of blood samples at room temperature caused significant changes in metabolome composition, but once the VAMS devices were stored at − 80 °C, the metabolome remained stable for up to 6 months. The time used for drying the sample did also affect the metabolome. In fact, some metabolites were rapidly degraded or accumulated in the sample during the first 48 h at room temperature, indicating that a longer drying step will significantly change the concentration in the sample. KeywordsMetabolomics; Volumetric absorptive microsampling; Mass spectrometry ✉ Giuseppe Paglia beppepaglia@gmail.com. Compliance with ethical standardsThis study was performed in accordance with the ethical standards. The local ethics committee (Comitato etico del comprensorio sanitario di Bolzano) approved the study, and all participants provided written informed consent.

show abstract

“…We demonstrated previously that RBCs consume adenine only until the end of phase 2, and that adenine consumption is correlated with the time of storage and not with its concentration in the storage solution. 33 Adenine is mostly consumed in phase 1. During phase 2, it is used to produce adenosine triphosphate through adenosine 59-monophosphate metabolism because during this phase pentose sugars are rerouted from pentose phosphate pathway into the adenosine 59-monophosphate metabolism through a nucleotide salvage pathway.…”

Section: Org Frommentioning

confidence: 99%

Biomarkers defining the metabolic age of red blood cells during cold storage

Paglia

D’Alessandro

Rolfsson

et al. 2016

Blood

Self Cite

127

View full text Add to dashboard Cite

• Eight extracellular biomarkers define the metabolic age of stored RBCs.• Metabolomics defines a universal signature of RBC storage lesion.Metabolomic investigations of packed red blood cells (RBCs) stored under refrigerated conditions in saline adenine glucose mannitol (SAGM) additives have revealed the presence of 3 distinct metabolic phases, occurring on days 0-10, 10-18, and after day 18 of storage. Here we used receiving operating characteristics curve analysis to identify biomarkers that can differentiate between the 3 metabolic states. We first recruited 24 donors and analyzed 308 samples coming from RBC concentrates stored in SAGM and additive solution 3. We found that 8 extracellular compounds (lactic acid, nicotinamide, 5-oxoproline, xanthine, hypoxanthine, glucose, malic acid, and adenine) form the basis for an accurate classification/regression model and are able to differentiate among the metabolic phases. This model was then validated by analyzing an additional 49 samples obtained by preparing 7 new RBC concentrates in SAGM. Despite the technical variability associated with RBC processing strategies, verification of these markers was independently confirmed in 2 separate laboratories with different analytical setups and different sample sets. The 8 compounds proposed here highly correlate with the metabolic age of packed RBCs, and can be prospectively validated as biomarkers of the RBC metabolic lesion. (Blood. 2016;128(13):e43-e50)

show abstract

Metabolic fate of adenine in red blood cells during storage in SAGM solution

Cited by 35 publications

References 30 publications

Heterogeneity of blood processing and storage additives in different centers impacts stored red blood cell metabolism as much as storage time: lessons from REDS‐III—Omics

Heterogeneity of blood processing and storage additives in different centers impacts stored red blood cell metabolism as much as storage time: lessons from REDS‐III—Omics

Pre-analytic evaluation of volumetric absorptive microsampling and integration in a mass spectrometry-based metabolomics workflow

Biomarkers defining the metabolic age of red blood cells during cold storage

Contact Info

Product

Resources

About