Few data-driven metabolomic approaches have been reported in sickle cell disease (SCD) to date. We performed a metabo-lipidomic study on the plasma and red blood cells of a steady-state mouse model carrying the homozygous human hemoglobin SS, compared with AS and AA genotypes. Among the 188 metabolites analyzed by a targeted quantitative metabolomic approach, 153 and 129 metabolites were accurately measured in the plasma and red blood cells, respectively. Unsupervised PCAs (principal component analyses) gave good spontaneous discrimination between HbSS and controls, and supervised OPLS-DAs (orthogonal partial least squares-discriminant analyses) provided highly discriminant models. These models confirmed the well-known deregulation of nitric oxide synthesis in the HbSS genotype, involving arginine deficiency and increased levels of dimethylarginines, ornithine, and polyamines. Other discriminant metabolites were newly evidenced, such as hexoses, alpha-aminoadipate, serotonin, kynurenine, and amino acids, pointing to a glycolytic shift and to the alteration of metabolites known to be involved in nociceptive pathways. Sharp remodeling of lysophosphatidylcholines, phosphatidylcholines, and sphingomyelins was evidenced in red blood cells. Our metabolomic study provides an overview of the metabolic remodeling induced by the sickle genotype in the plasma and red blood cells, revealing a biological fingerprint of altered nitric oxide, bioenergetics and nociceptive pathways.

中文翻译：

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镰状小鼠血浆和红细胞的代谢组学分析表明改变了伤害性途径。

迄今为止，很少有数据驱动的代谢组学方法用于镰状细胞病（SCD）。我们对携带纯合型人血红蛋白SS的稳态小鼠模型的血浆和红细胞与AS和AA基因型进行了血脂代谢研究。通过靶向定量代谢组学方法分析的188种代谢物中，分别在血浆和红细胞中准确测量了153种和129种代谢物。无监督的PCA（主要成分分析）在HbSS和对照之间提供了良好的自发区分，监督的OPLS-DA（正交偏最小二乘判别分析）提供了高判别模型。这些模型证实了HbSS基因型中一氧化氮合成的众所周知的失控，涉及精氨酸缺乏和二甲基精氨酸，鸟氨酸和多胺含量的增加。新发现了其他判别性代谢物，例如己糖，α-氨基己二酸酯，5-羟色胺，犬尿氨酸和氨基酸，表明糖酵解转移和已知参与伤害性途径的代谢物发生改变。在红细胞中发现溶血磷脂酰胆碱，磷脂酰胆碱和鞘磷脂的急剧重塑。我们的代谢组学研究概述了由镰刀基因型在血浆和红细胞中引起的代谢重塑，揭示了一氧化氮，生物能学和伤害性途径改变的生物学指纹。和氨基酸，这表明糖酵解转移和已知与伤害感受途径有关的代谢产物发生变化。在红细胞中发现溶血磷脂酰胆碱，磷脂酰胆碱和鞘磷脂的急剧重塑。我们的代谢组学研究概述了由镰刀基因型在血浆和红细胞中引起的代谢重塑，揭示了一氧化氮，生物能学和伤害性途径改变的生物学指纹。和氨基酸，指出糖酵解转移和已知参与伤害性途径的代谢物发生变化。在红细胞中发现溶血磷脂酰胆碱，磷脂酰胆碱和鞘磷脂的急剧重塑。我们的代谢组学研究概述了由镰刀基因型在血浆和红细胞中引起的代谢重塑，揭示了一氧化氮，生物能学和伤害性途径改变的生物学指纹。