Giuseppe Paglia1,2, Ólafur E Sigurjónsson3,4, Aarash Bordbar5, Óttar Rolfsson6, Manuela Magnusdottir6, Sirus Palsson6,5, Kristine Wichuk6, Sveinn Gudmundsson3, Bernhard O Palsson6. 1. Center for Biomedicine, European Academy of Bolzano/Bozen, Bolzano, Italy. giuseppe.paglia@eurac.edu. 2. Center for Systems Biology, University of Iceland, Reykjavik, Iceland;. giuseppe.paglia@eurac.edu. 3. The Blood Bank, Landspitali-University Hospital, Reykjavik, Iceland. 4. School of Science and Engineering, Reykjavik University, Reykjavik, Iceland; and. 5. Sinopia Biosciences, San Diego, California. 6. Center for Systems Biology, University of Iceland, Reykjavik, Iceland.
Abstract
BACKGROUND: Red blood cells (RBCs) are routinely stored and transfused worldwide. Recently, metabolomics have shown that RBCs experience a three-phase metabolic decay process during storage, resulting in the definition of three distinct metabolic phenotypes, occurring between Days 1 and 10, 11 and 17, and 18 and 46. Here we use metabolomics and stable isotope labeling analysis to study adenine metabolism in RBCs. STUDY DESIGN AND METHODS: A total of 6 units were prepared in SAGM or modified additive solutions (ASs) containing 15 N5 -adenine. Three of them were spiked with 15 N5 -adenine on Days 10, 14, and 17 during storage. Each unit was sampled 10 times spanning Day 1 to Day 32. At each time point metabolic profiling was performed. RESULTS: We increased adenine concentration in the AS and we pulsed the adenine concentration during storage and found that in both cases the RBCs' main metabolic pathways were not affected. Our data clearly show that RBCs cannot consume adenine after 18 days of storage, even if it is still present in the storage solution. However, increased levels of adenine influenced S-adenosylmethionine metabolism. CONCLUSION: In this work, we have studied in detail the metabolic fate of adenine during RBC storage in SAGM. Adenine is one of the main substrates used by RBCs, but the metabolic shift observed during storage is not caused by an absence of adenine later in storage. The rate of adenine consumption strongly correlated with duration of storage but not with the amount of adenine present in the AS.
BACKGROUND: Red blood cells (RBCs) are routinely stored and transfused worldwide. Recently, metabolomics have shown that RBCs experience a three-phase metabolic decay process during storage, resulting in the definition of three distinct metabolic phenotypes, occurring between Days 1 and 10, 11 and 17, and 18 and 46. Here we use metabolomics and stable isotope labeling analysis to study adenine metabolism in RBCs. STUDY DESIGN AND METHODS: A total of 6 units were prepared in SAGM or modified additive solutions (ASs) containing 15 N5 -adenine. Three of them were spiked with 15 N5 -adenine on Days 10, 14, and 17 during storage. Each unit was sampled 10 times spanning Day 1 to Day 32. At each time point metabolic profiling was performed. RESULTS: We increased adenine concentration in the AS and we pulsed the adenine concentration during storage and found that in both cases the RBCs' main metabolic pathways were not affected. Our data clearly show that RBCs cannot consume adenine after 18 days of storage, even if it is still present in the storage solution. However, increased levels of adenine influenced S-adenosylmethionine metabolism. CONCLUSION: In this work, we have studied in detail the metabolic fate of adenine during RBC storage in SAGM. Adenine is one of the main substrates used by RBCs, but the metabolic shift observed during storage is not caused by an absence of adenine later in storage. The rate of adenine consumption strongly correlated with duration of storage but not with the amount of adenine present in the AS.
Authors: Angelo D'Alessandro; Julie A Reisz; Rachel Culp-Hill; Herbert Korsten; Robin van Bruggen; Dirk de Korte Journal: Transfusion Date: 2018-04-06 Impact factor: 3.157
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Authors: Julie A Reisz; Travis Nemkov; Monika Dzieciatkowska; Rachel Culp-Hill; Davide Stefanoni; Ryan C Hill; Tatsuro Yoshida; Andrew Dunham; Tamir Kanias; Larry J Dumont; Michael Busch; Elan Z Eisenmesser; James C Zimring; Kirk C Hansen; Angelo D'Alessandro Journal: Transfusion Date: 2018-10-12 Impact factor: 3.157
Authors: Angelo D'Alessandro; Rachel Culp-Hill; Julie A Reisz; Mikayla Anderson; Xiaoyun Fu; Travis Nemkov; Sarah Gehrke; Connie Zheng; Tamir Kanias; Yuelong Guo; Grier Page; Mark T Gladwin; Steve Kleinman; Marion Lanteri; Mars Stone; Michael Busch; James C Zimring Journal: Transfusion Date: 2018-10-24 Impact factor: 3.157
Authors: Aline Roch; Nicholas J Magon; Jessica Maire; Cacang Suarna; Anita Ayer; Sophie Waldvogel; Beat A Imhof; Mark J Koury; Roland Stocker; Marc Schapira Journal: JCI Insight Date: 2019-11-01
Authors: Chiara Volani; Giulia Caprioli; Giovanni Calderisi; Baldur B Sigurdsson; Johannes Rainer; Ivo Gentilini; Andrew A Hicks; Peter P Pramstaller; Guenter Weiss; Sigurdur V Smarason; Giuseppe Paglia Journal: Anal Bioanal Chem Date: 2017-08-17 Impact factor: 4.142