Role of band 3 in regulating metabolic flux of red blood cells.
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ABSTRACT:
SUBMITTER: Lewis IA
PROVIDER: S-EPMC2773988 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundRed blood cell exchange (RCE) transfusions are a mainstay in the treatment of sickle cell anemia (SCA), and allow a temporary restoration of physiological parameters with respect to erythrocyte oxygen carrying capacity and systems metabolism. Recently, we noted that 1) RCE significantly impacts recipients' metabolism in SCA; 2) fresh and end-of-storage red blood cell (RBC) units differently impact systems of metabolism in healthy autologous recipients; and 3) phosphate/inosine/pyruvate/adenine (PIPA) solution reverses the metabolic age of stored RBCs. Therefore, we hypothesized that RCE with PIPA-treated RBC units could further increase the metabolic benefits of RCE in SCA patients.Study design and methodsCirculating plasma and erythrocytes were collected from patients with SCA before and after RCE, with either conventional or PIPA-treated RBC units, prior to metabolomics analyses.ResultsConsistent with prior work, RCE significantly decreased circulating levels of markers of systemic hypoxemia (lactate, succinate) and decreased plasma levels of acyl-carnitines and amino acids. However, PIPA-treated exchanges were superior to untreated RCEs, with a higher energy state and an increased capacity to activate the pentose phosphate pathway and glutamine metabolism. In addition, RBCs and plasma from recipients of PIPA-treated RBC units resulted in significantly decreased levels of post-transfusion plasticizers, though at the expense of higher circulating levels of oxidized purines (hypoxanthine, xanthine, and the antioxidant urate).ConclusionTransfusion of PIPA-treated RBCs further increases the metabolic benefits of RCE to patients with SCA, significantly reducing the levels of post-transfusion plasticizers.
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Project description:Aging is a physiological process whose underlying mechanisms are still largely unknown. The study of the biochemical transformations associated with aging is crucial for understanding this process and could translate into an improvement of the quality of life of the aging population. Red blood cells (RBCs) are the most abundant cells in humans and are involved in essential functions that could undergo different alterations with age. The present study analyzed the metabolic alterations experienced by RBCs during aging, as well as the influence of obesity and gender in this process. To this end, the metabolic profile of 83 samples from healthy and obese patients was obtained by Nuclear Magnetic Resonance spectroscopy. Multivariate statistical analysis revealed differences between Age-1 (≤45) and Age-2 (>45) subgroups, as well as between BMI-1 (<30) and BMI-2 (≥30) subgroups, while no differences were associated with gender. A general decrease in the levels of amino acids was detected with age, in addition to metabolic alterations of glycolysis, the pentose phosphate pathway, nucleotide metabolism, glutathione metabolism and the Luebering-Rapoport shunt. Obesity also had an impact on the metabolomics profile of RBCs; sometimes mimicking the alterations induced by aging, while, in other cases, its influence was the opposite, suggesting these changes could counteract the adaptation of the organism to senescence.
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Project description:Anaerobic red blood cell (RBC) storage reduces oxidative damage, maintains adenosine triphosphate (ATP) and 2,3-diphosphoglycerate (DPG) levels, and has superior 24-hour recovery at 6 weeks compared to standard storage. This study will determine if removal of CO2 during O2 depletion by gas exchange may affect RBCs during anaerobic storage.This is a matched three-arm study (n?=?14): control, O2 and CO2 depleted with Ar (AN), and O2 depleted with 95%Ar/5%CO2 (AN[CO2 ]). RBCs in additives AS-3 or OFAS-3 were evenly divided into three bags, and anaerobic conditions were established by gas exchange. Bags were stored at 1 to 6°C in closed chambers under anaerobic conditions or ambient air, sampled weekly for up to 9 weeks for a panel of in vitro tests. A full metabolomics screening was conducted for the first 4 weeks of storage.Purging with Ar (AN) results in alkalization of the RBC and increased glucose consumption. The addition of 5% CO2 to the purging gas prevented CO2 loss with an equivalent starting and final pH and lactate to control bags (p?>?0.5, Days 0-21). ATP levels are higher in AN[CO2 ] (p?<?0.0001). DPG was maintained beyond 2 weeks in the AN arm (p?<?0.0001). Surprisingly, DPG was lost at the same rate in both control and AN[CO2 ] arms (p?=?0.6).Maintenance of ATP in the AN[CO2 ] arm demonstrates that ATP production is not solely a function of the pH effect on glycolysis. CO2 in anaerobic storage prevented the maintenance of DPG, and DPG production appears to be pH dependent. CO2 as well as O2 depletion provides metabolic advantage for stored RBCs.
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