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Metabolomic Profiling of Aqueous Humor in Glaucoma Points to Taurine and Spermine Deficiency: Findings from the Eye-D Study.
Journal of Proteome Research ( IF 4.4 ) Pub Date : 2019-02-11 , DOI: 10.1021/acs.jproteome.8b00915
Adrien Buisset 1 , Philippe Gohier 1 , Stéphanie Leruez 1, 2 , Jeanne Muller 1 , Patrizia Amati-Bonneau 2, 3 , Guy Lenaers 2 , Dominique Bonneau 2, 3 , Gilles Simard 3 , Vincent Procaccio 2, 3 , Cédric Annweiler 4, 5 , Dan Milea 6 , Pascal Reynier 2, 3 , Juan Manuel Chao de la Barca 2, 3
Affiliation  

We compared the metabolomic profile of aqueous humor from patients with primary open-angle glaucoma (POAG; n = 26) with that of a group of age- and sex-matched non-POAG controls (n = 26), all participants undergoing cataract surgery. Supervised paired partial least-squares discriminant analysis showed good predictive performance for test sets with a median area under the receiver operating characteristic of 0.89 and a p-value of 0.0087. Twenty-three metabolites allowed discrimination between the two groups. Univariate analysis after the Benjamini-Hochberg correction showed significant differences for 13 of these metabolites. The POAG metabolomic signature indicated reduced concentrations of taurine and spermine and increased concentrations of creatinine, carnitine, three short-chain acylcarnitines, 7 amino acids (glutamine, glycine, alanine, leucine, isoleucine, hydroxyl-proline, and acetyl-ornithine), 7 phosphatidylcholines, one lysophosphatidylcholine, and one sphingomyelin. This suggests an alteration of metabolites involved in osmoprotection (taurine and creatinine), neuroprotection (spermine, taurine, and carnitine), amino acid metabolism (7 amino acids and three acylcarnitines), and the remodeling of cell membranes drained by the aqueous humor (hydroxyproline and phospholipids). Five of these metabolic alterations, already reported in POAG plasma, concern spermine, C3 and C4 acylcarnitines, PC aa 34:2, and PC aa 36:4, thus highlighting their importance in the pathogenesis of glaucoma.

中文翻译:

青光眼水体幽默的代谢组学分析表明牛磺酸和精胺缺乏:Eye-D研究的发现。

我们比较了原发性开角型青光眼(POAG; n = 26)患者与一组年龄和性别相匹配的非POAG对照(n = 26)的房水的代谢组学特征,所有参与者均接受了白内障手术。监督配对偏最小二乘判别分析显示测试集具有良好的预测性能,其中接收器操作特征下的中值面积为0.89,p值为0.0087。23种代谢物允许在两组之间进行区分。Benjamini-Hochberg校正后的单变量分析显示,这些代谢物中的13种存在显着差异。POAG的代谢组学特征表明牛磺酸和精胺的浓度降低,肌酐,肉碱,三种短链酰基肉碱,7个氨基酸(谷氨酰胺,甘氨酸,丙氨酸,亮氨酸,异亮氨酸,羟脯氨酸和乙酰鸟氨酸),7个磷脂酰胆碱,1个溶血磷脂酰胆碱和1个鞘磷脂。这表明涉及渗透保护(牛磺酸和肌酐),神经保护(精胺,牛磺酸和肉碱),氨基酸代谢(7个氨基酸和三个酰基肉碱)的代谢物发生改变,以及房水排出的细胞膜重塑(羟脯氨酸)和磷脂)。在POAG血浆中已经报道的这些代谢改变中有五个涉及精胺,C3和C4酰基肉碱,PCaa 34:2和PCaa 36:4,因此突出了它们在青光眼发病机理中的重要性。这表明涉及渗透保护(牛磺酸和肌酐),神经保护(精胺,牛磺酸和肉碱),氨基酸代谢(7个氨基酸和三个酰基肉碱)的代谢物发生改变,以及房水排出的细胞膜重塑(羟脯氨酸)和磷脂)。在POAG血浆中已经报道的这些代谢改变中有五个涉及精胺,C3和C4酰基肉碱,PCaa 34:2和PCaa 36:4,因此突出了它们在青光眼发病机理中的重要性。这表明涉及渗透保护(牛磺酸和肌酐),神经保护(精胺,牛磺酸和肉碱),氨基酸代谢(7个氨基酸和三个酰基肉碱)的代谢物发生改变,以及房水排出的细胞膜重塑(羟脯氨酸)和磷脂)。在POAG血浆中已经报道的这些代谢改变中有五个涉及精胺,C3和C4酰基肉碱,PCaa 34:2和PCaa 36:4,因此突出了它们在青光眼发病机理中的重要性。
更新日期:2019-02-13
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