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Quantifying dynamic range in red blood cell energetics: Evidence of progressive energy failure during storage
Author(s) -
Rogers Stephen C.,
Ge Xia,
Brummet Mary,
Lin Xue,
Timm David D.,
d'Avig Andre,
Garbow Joel R.,
Kao Jeff,
Prakash Jaya,
Issaian Aaron,
Eisenmesser Elan Z.,
Reisz Julie A.,
D'Alessandro Angelo,
Doctor Allan
Publication year - 2021
Publication title -
transfusion
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.045
H-Index - 132
eISSN - 1537-2995
pISSN - 0041-1132
DOI - 10.1111/trf.16395
Subject(s) - glycolysis , chemistry , red blood cell , hypoxanthine , biochemistry , oxidative stress , antioxidant , flux (metallurgy) , metabolic flux analysis , glutathione , metabolomics , biophysics , metabolism , biology , chromatography , enzyme , organic chemistry
Background During storage, red blood cells (RBCs) undergo significant biochemical and morphologic changes, referred to collectively as the “storage lesion”. It was hypothesized that these defects may arise from disrupted oxygen‐based regulation of RBC energy metabolism, with resultant depowering of intrinsic antioxidant systems. Study Design and Methods As a function of storage duration, the dynamic range in RBC metabolic response to three models of biochemical oxidant stress (methylene blue, hypoxanthine/xanthine oxidase, and diamide) was assessed, comparing glycolytic flux by NMR and UHPLC–MS methodologies. Blood was processed/stored under standard conditions (AS‐1 additive solution) with leukoreduction. Over a 6‐week period, RBC metabolic and antioxidant status were assessed at baseline and following exposure to the three biochemical oxidant models. Comparison was made of glycolytic flux ( 1 H‐NMR tracking of [2‐ 13 C]‐glucose and metabolomic phenotyping with [1,2,3‐ 13 C 3 ] glucose), reducing equivalent (NADPH/NADP + ) recycling, and thiol‐based (GSH/GSSG) antioxidant status. Results As a function of storage duration, we observed the following: (1) a reduction in baseline hexose monophosphate pathway (HMP) flux, the sole pathway responsible for the regeneration of the essential reducing equivalent NADPH; with (2) diminished stress‐based dynamic range in both overall glycolytic as well as proportional HMP flux. In addition, progressive with storage duration, RBCs showed (3) constraint in reducing equivalent (NADPH) recycling capacity, (4) loss of thiol based (GSH) recycling capacity, and (5) dysregulation of metabolon assembly at the cytoplasmic domain of Band 3 membrane protein (cdB3). Conclusion Blood storage disturbs normal RBC metabolic control, depowering antioxidant capacity and enhancing vulnerability to oxidative injury.