Bertolone Lorenzo, Shin Hye Kyung H, Baek Jin Hyen, Gao Yamei, 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. 2022 Mar 21;13:845347. doi: 10.3389/fphys.2022.845347. eCollection 2022.
Unlike other rodents, guinea pigs () have evolutionarily lost their capacity to synthesize vitamin C (ascorbate) 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 ( = 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 ( = 21), olive baboons ( = 20), and rhesus macaques ( = 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.
与其他啮齿动物不同，豚鼠在进化过程中失去了合成维生素C（抗坏血酸）的能力，与一些非人类灵长类动物和人类一样，它们依靠饮食摄入和谷胱甘肽依赖性循环来应对氧化应激。这在红细胞生理学中尤为重要，尤其是在模拟血液储存时，这会加剧红细胞氧化应激。在此，我们对新鲜和储存的豚鼠红细胞浓缩物（n = 20）进行了全面的代谢组学分析，从储存第0天到第42天每周取样一次。将结果与之前发表的关于另外三种L-古洛糖酸内酯氧化酶功能基因缺失物种红细胞的ZOOMICS研究进行比较，包括人类（n = 21）、橄榄狒狒（n = 20）和恒河猴（n = 20）。虽然所有物种的代谢趋势具有可比性，但豚鼠红细胞显示出与氧化应激一致的储存损伤代谢标志物的加速变化。与其他物种相比，豚鼠红细胞表现出异常的糖酵解、磷酸戊糖途径终产物代谢物、嘌呤分解产物、甲基化、谷氨酰胺分解以及膜脂质重塑标志物。一致的是，与其他物种相比，豚鼠红细胞在储存末期表现出更高的溶血率，扫描电子显微镜证实其红细胞形态改变程度更高。尽管所评估的物种普遍存在遗传上无法产生抗坏血酸的情况，但豚鼠红细胞在标准储存条件下仍表现出加速的氧化应激。这些数据可能为无法合成内源性抗坏血酸的物种红细胞的基础代谢和冷藏代谢提供相关见解。
