Red blood cell storage in additive solution-7 preserves energy and redox metabolism: a metabolomics approach
Corresponding Author
Angelo D'Alessandro
Department of Biochemistry and Molecular Genetics, University of Colorado Denver–Anschutz Medical Campus, Aurora, Colorado
Address reprint requests to: Angelo D'Alessandro, Department of Biochemistry and Molecular Genetics, University of Colorado Denver Anschutz Medical Campus, Aurora, CO 80045; e-mail: [email protected]; or Larry J. Dumont, Geisel School of Medicine at Dartmouth, One Medical Center Drive, Lebanon, NH 03756-0001; e-mail: [email protected].Search for more papers by this authorTravis Nemkov
Department of Biochemistry and Molecular Genetics, University of Colorado Denver–Anschutz Medical Campus, Aurora, Colorado
Search for more papers by this authorKirk C. Hansen
Department of Biochemistry and Molecular Genetics, University of Colorado Denver–Anschutz Medical Campus, Aurora, Colorado
Search for more papers by this authorZbigniew M. Szczepiorkowski
Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire
Search for more papers by this authorCorresponding Author
Larry J. Dumont
Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire
Address reprint requests to: Angelo D'Alessandro, Department of Biochemistry and Molecular Genetics, University of Colorado Denver Anschutz Medical Campus, Aurora, CO 80045; e-mail: [email protected]; or Larry J. Dumont, Geisel School of Medicine at Dartmouth, One Medical Center Drive, Lebanon, NH 03756-0001; e-mail: [email protected].Search for more papers by this authorCorresponding Author
Angelo D'Alessandro
Department of Biochemistry and Molecular Genetics, University of Colorado Denver–Anschutz Medical Campus, Aurora, Colorado
Address reprint requests to: Angelo D'Alessandro, Department of Biochemistry and Molecular Genetics, University of Colorado Denver Anschutz Medical Campus, Aurora, CO 80045; e-mail: [email protected]; or Larry J. Dumont, Geisel School of Medicine at Dartmouth, One Medical Center Drive, Lebanon, NH 03756-0001; e-mail: [email protected].Search for more papers by this authorTravis Nemkov
Department of Biochemistry and Molecular Genetics, University of Colorado Denver–Anschutz Medical Campus, Aurora, Colorado
Search for more papers by this authorKirk C. Hansen
Department of Biochemistry and Molecular Genetics, University of Colorado Denver–Anschutz Medical Campus, Aurora, Colorado
Search for more papers by this authorZbigniew M. Szczepiorkowski
Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire
Search for more papers by this authorCorresponding Author
Larry J. Dumont
Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire
Address reprint requests to: Angelo D'Alessandro, Department of Biochemistry and Molecular Genetics, University of Colorado Denver Anschutz Medical Campus, Aurora, CO 80045; e-mail: [email protected]; or Larry J. Dumont, Geisel School of Medicine at Dartmouth, One Medical Center Drive, Lebanon, NH 03756-0001; e-mail: [email protected].Search for more papers by this authorThis article was published online on 14 AUG 2015. An error was subsequently identified. This notice is included in the online and print versions to indicate that both have been corrected 29 September 2015.
Abstract
BACKGROUND
Storage and transfusion of red blood cells (RBCs) has a huge medical and economic impact. Routine storage practices can be ameliorated through the implementation of novel additive solutions (ASs) that tackle the accumulation of biochemical and morphologic lesion during routine cold liquid storage in the blood bank, such as the recently introduced alkaline solution AS-7. Here we hypothesize that AS-7 might exert its beneficial effects through metabolic modulation during routine storage.
STUDY DESIGN AND METHODS
Apheresis RBCs were resuspended either in control AS-3 or experimental AS-7, before ultrahigh-performance liquid chromatography–mass spectrometry metabolomics analysis.
RESULTS
Unambiguous assignment and relative quantitation was achieved for 229 metabolites. AS-3 and AS-7 results in many similar metabolic trends over storage, with AS-7 RBCs being more metabolically active in the first storage week. AS-7 units had faster fueling of the pentose phosphate pathway, higher total glutathione pools, and increased flux through glycolysis as indicated by higher levels of pathway intermediates. Metabolite differences are especially observed at 7 days of storage, but were still maintained throughout 42 days.
CONCLUSION
AS-7 formulation (chloride free and bicarbonate loading) appears to improve energy and redox metabolism in stored RBCs in the early storage period, and the differences, though diminished, are still appreciable by Day 42. Energy metabolism and free fatty acids should be investigated as potentially important determinants for preservation of RBC structure and function. Future studies will be aimed at identifying metabolites that correlate with in vitro and in vivo circulation times.
Supporting Information
Additional Supporting Information may be found in the online version of this article at the publisher's website:
| Filename | Description |
|---|---|
| trf13253-sup-0001-suppinfo01.pdf2.7 MB | Fig. S1. Extract ion chromatogram for mannitol in AS-3 vs AS-7 samples. |
| trf13253-sup-0002-suppinfo02.pdf193.6 KB |
Fig. S2. Hierarchical Clustering Analysis of metabolites levels in red blood cell extracts during storage in AS-3 or AS-7. Heat maps display intra-row normalized quantitative fluctuations for each metabolite (blue to red = low to high levels), as detected through UHPLC-MS metabolomics analyses of red blood cell extracts during storage in AS-3 or AS-7. Metabolite names are indicated on the right side of the figure, while storage time points are indicated on top of the map and are annotated through the color code explicated in the top left corner of the figure. |
| trf13253-sup-0003-suppinfo03.pdf1.1 MB |
Table S1. Sheets 1 to 7 (vectorial - ∞ zoom in) |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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