Bertolone Lorenzo, Shin Hye K, Stefanoni Davide, Baek Jin Hyen, Gao Yamei, Morrison Evan J, Nemkov Travis, Thomas Tiffany, Francis Richard O, Hod Eldad A, Zimring James C, Yoshida Tatsuro, Karafin Matthew, Schwartz Joseph, Hudson Krystalyn E, Spitalnik Steven L, Buehler Paul W, D'Alessandro Angelo
Department of Biochemistry and Molecular Genetics, University of Colorado Denver - Anschutz Medical Campus, Aurora, CO, United States.
Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD, United States.
Front Physiol. 2020 Oct 23;11:593841. doi: 10.3389/fphys.2020.593841. eCollection 2020.
As part of the ZOOMICS project, we set out to investigate common and diverging metabolic traits in the blood metabolome across various species by taking advantage of recent developments in high-throughput metabolomics. Here we provide the first comparative metabolomics analysis of fresh and stored human ( = 21, 10 males, 11 females), olive baboon ( = 20), and rhesus macaque ( = 20) red blood cells at baseline and upon 42 days of storage under blood bank conditions. The results indicated similarities and differences across species, which ultimately resulted in a differential propensity to undergo morphological alterations and lyse as a function of the duration of refrigerated storage. Focusing on purine oxidation, carboxylic acid, fatty acid, and arginine metabolism further highlighted species-specific metabolic wiring. For example, through a combination of steady state measurements and C N-arginine tracing experiments, we report an increase in arginine catabolism into ornithine in humans, suggestive of species-specific arginase 1 activity and nitric oxide synthesis-an observation that may impact the translatability of cardiovascular disease studies carried out in non-human primates (NHPs). Finally, we correlated metabolic measurements to storage-induced morphological alterations via scanning electron microscopy and hemolysis, which were significantly lower in human red cells compared to both NHPs.
作为“ZOOMICS项目”的一部分，我们利用高通量代谢组学的最新进展，着手研究不同物种血液代谢组中常见和不同的代谢特征。在此，我们首次对新鲜和储存的人类（n = 21，10名男性，11名女性）、橄榄狒狒（n = 20）和恒河猴（n = 20）红细胞在基线时以及在血库条件下储存42天后进行了比较代谢组学分析。结果表明不同物种之间存在异同，最终导致根据冷藏储存时间长短，发生形态改变和溶血的倾向有所不同。关注嘌呤氧化、羧酸、脂肪酸和精氨酸代谢进一步突出了物种特异性的代谢途径。例如，通过稳态测量和¹³C¹⁵N-精氨酸示踪实验相结合，我们报告了人类中精氨酸分解代谢为鸟氨酸的增加，这表明存在物种特异性的精氨酸酶1活性和一氧化氮合成——这一观察结果可能会影响在非人类灵长类动物（NHP）中进行的心血管疾病研究的可转化性。最后，我们通过扫描电子显微镜和溶血将代谢测量结果与储存诱导的形态改变相关联，与两种NHP相比，人类红细胞中的这些改变明显更低。
