Red blood cell metabolism under prolonged anaerobic storage

Abstract

Oxygen dependent modulation of red blood cell metabolism is a long investigated issue. However, the recent introduction of novel mass spectrometry-based approaches lends itself to implement our understanding of the effects of red blood cell prolonged exposure to anaerobiosis. Indeed, most of the studies conducted so far have addressed the short term issue, while the limited body of literature covering a 42 days storage period only takes into account a handful of metabolic parameters (ATP, DPG, glucose, glyceraldehyde 3-phosphate, and lactate). We hereby performed a mass spectrometry-based untargeted metabolomics analysis in order to highlight metabolic species in erythrocyte concentrates stored anaerobically in SAGM additive solutions for up to 42 days, by testing cells on a weekly basis. We could confirm previous evidence about long term anaerobiosis promoting glycolytic metabolism in RBCs and prolonging the conservation of high energy phosphate reservoirs and purine homeostasis. In parallel, we evidenced that, in contrast to aerobic storage, anaerobiosis impairs erythrocyte capacity to cope with oxidative stress by blocking metabolic diversion towards the pentose phosphate pathway, which negatively affects glutathione homeostasis. Therefore, although oxidative stress was less sustained than in aerobically stored counterparts, oxidative stress markers still accumulate over anaerobic storage progression.

AltitudeOmics: Red Blood Cell Metabolic Adaptation to High Altitude Hypoxia

“…26–29 According to this model, 26–29 as much as 92% of glucose is catabolized through the classic Embden-Meyerhoff glycolytic pathway under normoxia, while anoxia triggers consumption of as much as 90% of glucose via the PPP. This model has been supported by in vitro evidence 30 and in silico prediction based on metabolomics data of ex vivo aging RBCs under anaerobic conditions 31,32 . However, evidence of in vivo RBC metabolic adaptations to hypoxia has not been hitherto produced.…”

An Efficient Apparatus for Rapid Deoxygenation of Erythrocyte Concentrates for Alternative Banking Strategies

“…On the other hand, we recently proposed a detailed study about the alterations to the metabolic fluxes upon deoxygenation and over storage duration on a weekly basis [32] and compared the results to our in-depth analyses on CPD-SAGM-stored untreated RBCs [33]. From this study, it emerged that the deoxygenation of RBCs might result in the alteration of the redox poise by upmodulating the nitric oxide (NO) metabolism, which is known to influence the production of RNS, and by blocking the oxidative stress-triggered metabolic diversion from the Emden Meyerhof classic glycolytic pathway towards the pentose phosphate pathway, which should instead provide reduced coenzymes to regenerate the antioxidant battery, such as NADPH) [31].…”

Heritability of glutathione and related metabolites in stored red blood cells

“…The concentration and stability of these metabolites during the storage of RBCs has been associated with the RBC storage lesion [13, 17, 19, 43, 44]. Supplementation of stored RBCs with GSH has been shown to partially protect from free radical and oxidant-induced injury, thereby maintaining more normal cellular function [12, 16].…”

“…Supplementation of stored RBCs with GSH has been shown to partially protect from free radical and oxidant-induced injury, thereby maintaining more normal cellular function [12, 16]. Recently, methods have been explored for storing RBC units anaerobically with the goal of reducing oxidative damage throughout the storage period [43]. Efforts such as these to improve RBC storage by preventing oxidative damage may benefit from identifying and understanding the genetic modifiers that influence GSH and related metabolites during storage.…”