Donor sex, age and ethnicity impact stored red blood cell antioxidant metabolism through mechanisms in part explained by glucose 6-phosphate dehydrogenase levels and activity.
Donor sex, age and ethnicity impact stored red blood cell antioxidant metabolism through mechanisms in part explained by glucose 6-phosphate dehydrogenase levels and activity.
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DOI：
10.3324/haematol.2020.246603
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发表时间：
2021-05-01
期刊：
影响因子：
10.1
通讯作者：
Recipient Epidemiology and Donor Evaluation Study-III (REDS III)
中科院分区：
文献类型：
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作者：
D'Alessandro A;Fu X;Kanias T;Reisz JA;Culp-Hill R;Guo Y;Gladwin MT;Page G;Kleinman S;Lanteri M;Stone M;Busch MP;Zimring JC;Recipient Epidemiology and Donor Evaluation Study-III (REDS III)
血库中红细胞（RBC）的储存会促使代谢变化逐渐累积，这最终可能影响红细胞应对氧化应激源的能力。然而，红细胞抵抗氧化应激能力的代谢基础以及供体生物学对这种表型的潜在影响尚不清楚。在REDS - III红细胞组学研究的框架内，来自8502名健康献血者的红细胞储存了42天，并测试了它们在氧化应激后溶血的倾向。一部分极端溶血者捐献了第二单位血液，这些血液分别储存10天、23天和42天，并再次对氧化溶血和代谢组学进行分析（599个样本）。在高氧化溶血的供体中，观察到红细胞能量和氧化还原内稳态的改变。与男性、30岁以下供体、西班牙裔和非裔美国人种族供体以及储存在添加剂溶液 - 1中的红细胞相比，女性供体、60岁以上供体、亚洲/南亚种族供体的红细胞以及储存在添加剂溶液 - 3中的红细胞各自具有改善的抗氧化代谢特征。将代谢组学数据与对同一队列进行的独立全基因组关联研究的结果相结合，我们确定了溶血和葡萄糖 - 6 - 磷酸脱氢酶缺乏的代谢标志物，这些标志物与氧化溶血的极端情况以及烟酰胺腺嘌呤二核苷酸磷酸和谷胱甘肽依赖性氧化脂质解毒途径的失调有关。供体性别、年龄、种族、添加剂溶液以及葡萄糖 - 6 - 磷酸脱氢酶状态会影响储存红细胞的代谢及其在遭受氧化损伤后溶血的敏感性。
Red blood cell (RBC) storage in the blood bank promotes the progressive accumulation of metabolic alterations that may ultimately impact the erythrocyte capacity to cope with oxidant stressors. However, the metabolic underpinnings of the capacity of RBC to resist oxidant stress and the potential impact of donor biology on this phenotype are not known. Within the framework of the REDS-III RBC-Omics study, RBC from 8,502 healthy blood donors were stored for 42 days and tested for their propensity to hemolyse following oxidant stress. A subset of extreme hemolysers donated a second unit of blood, which was stored for 10, 23, and 42 days and profiled again for oxidative hemolysis and metabolomics (599 samples). Alterations of RBC energy and redox homeostasis were noted in donors with high oxidative hemolysis. RBC from females, donors over 60 years old, donors of Asian/South Asian race-ethnicity, and RBC stored in additive solution- 3 were each independently characterized by improved antioxidant metabolism compared to, respectively, males, donors under 30 years old, Hispanic and African American race ethnicity donors, and RBC stored in additive solution-1. Merging metabolomics data with results from an independent genome-wide association study on the same cohort, we identified metabolic markers of hemolysis and glucose 6-phosphate dehydrogenasedeficiency, which were associated with extremes in oxidative hemolysis and dysregulation in nicotinamide adenine dinucleotide phosphate and glutathione- dependent detoxification pathways of oxidized lipids. Donor sex, age, ethnicity, additive solution and glucose 6-phosphate dehydrogenase status impact the metabolism of the stored erythrocyte and its susceptibility to hemolysis following oxidative insults.