ZOOMICS: Comparative Metabolomics of Red Blood Cells From Guinea Pigs, Humans, and Non-human Primates During Refrigerated Storage for Up to 42 Days

Lorenzo Bertolone; Hye Kyung H Shin; Jin Hyen Baek; Yamei Gao; Steven L Spitalnik; Paul W Buehler; Angelo D'Alessandro

doi:10.3389/fphys.2022.845347

ZOOMICS: Comparative Metabolomics of Red Blood Cells From Guinea Pigs, Humans, and Non-human Primates During Refrigerated Storage for Up to 42 Days

Front Physiol. 2022 Mar 21:13:845347. doi: 10.3389/fphys.2022.845347. eCollection 2022.

Authors

Lorenzo Bertolone¹, Hye Kyung H Shin², Jin Hyen Baek², Yamei Gao², Steven L Spitalnik³, Paul W Buehler^{4

5}, Angelo D'Alessandro^{1

6}

Affiliations

¹ Department of Biochemistry and Molecular Genetics, University of Colorado Denver - Anschutz Medical Campus, Aurora, CO, United States.
² Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD, United States.
³ Department of Pathology and Cell Biology, Columbia University, New York, NY, United States.
⁴ Department of Pathology, University of Maryland School of Medicine, Baltimore, MD, United States.
⁵ Department of Pediatrics, Center for Blood Oxygen Transport and Hemostasis, University of Maryland School of Medicine, Baltimore, MD, United States.
⁶ Department of Medicine, Division of Hematology, University of Colorado Denver - Anschutz Medical Campus, Aurora, CO, United States.

Abstract

Unlike other rodents, guinea pigs (Cavia porcellus) have evolutionarily lost their capacity to synthesize vitamin C (ascorbate) de novo and, like several non-human primates and humans, rely on dietary intake and glutathione-dependent recycling to cope with oxidant stress. This is particularly relevant in red blood cell physiology, and especially when modeling blood storage, which exacerbates erythrocyte oxidant stress. Herein we provide a comprehensive metabolomics analysis of fresh and stored guinea pig red blood cell concentrates (n = 20), with weekly sampling from storage day 0 through 42. Results were compared to previously published ZOOMICS studies on red blood cells from three additional species with genetic loss of L-gulonolactone oxidase function, including humans (n = 21), olive baboons (n = 20), and rhesus macaques (n = 20). While metabolic trends were comparable across all species, guinea pig red blood cells demonstrated accelerated alterations of the metabolic markers of the storage lesion that are consistent with oxidative stress. Compared to the other species, guinea pig red blood cells showed aberrant glycolysis, pentose phosphate pathway end product metabolites, purine breakdown products, methylation, glutaminolysis, and markers of membrane lipid remodeling. Consistently, guinea pig red blood cells demonstrated higher end storage hemolysis, and scanning electron microscopy confirmed a higher degree of morphological alterations of their red blood cells, as compared to the other species. Despite a genetic inability to produce ascorbate that is common to the species evaluated, guinea pig red blood cells demonstrate accelerated oxidant stress under standard storage conditions. These data may offer relevant insights into the basal and cold storage metabolism of red blood cells from species that cannot synthesize endogenous ascorbate.

Keywords: ascorbate; comparative biology; erythrocyte; hemolysis; metabolomics; rodent.

Abstract

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