用于监测弗里德赖希共济失调血小板代谢紊乱的稳定同位素与液相色谱-质谱联用技术
Stable isotopes and LC-MS for monitoring metabolic disturbances in Friedreich's ataxia platelets.
作者信息
Worth Andrew J, Basu Sankha S, Deutsch Eric C, Hwang Wei-Ting, Snyder Nathaniel W, Lynch David R, Blair Ian A
机构信息
Center of Excellence in Environmental Toxicology, University of Pennsylvania, Philadelphia, PA 19104, USA.
Penn SRP Center, University of Pennsylvania, Philadelphia, PA 19104, USA.
出版信息
Bioanalysis. 2015;7(15):1843-55. doi: 10.4155/bio.15.118.
BACKGROUND
Friedreich's ataxia (FRDA) is an autosomal recessive disease with metabolic abnormalities that have been proposed to play an important role in the resulting neurodegeneration and cardiomyopathy. The inability to access the highly affected neuronal and cardiac tissues has hampered metabolic evaluation and biomarker development.
METHODS
Employment of a LC-MS-based method to determine whether platelets isolated from patients with FRDA exhibit differentiable metabolism compared with healthy controls.
RESULTS
Isotopologue analysis showed a marked decrease in glucose incorporation with a concomitant increase in palmitate-derived acyl-CoA thioesters in FRDA platelets compared with controls.
CONCLUSION
Our findings demonstrate that platelets can be used as a surrogate tissue for in vivo biomarker studies to monitor new therapeutic approaches for the treatment of FRDA.
背景
弗里德赖希共济失调（FRDA）是一种常染色体隐性疾病，伴有代谢异常，这种异常被认为在由此导致的神经变性和心肌病中起重要作用。无法获取受影响严重的神经组织和心脏组织阻碍了代谢评估和生物标志物的开发。
方法
采用基于液相色谱 - 质谱联用的方法，以确定与健康对照相比，从FRDA患者分离出的血小板是否表现出可区分的代谢。
结果
同位素异构体分析表明，与对照组相比，FRDA血小板中葡萄糖掺入量显著降低，同时棕榈酸衍生的酰基辅酶A硫酯增加。
结论
我们的研究结果表明，血小板可作为体内生物标志物研究的替代组织，以监测治疗FRDA的新治疗方法。
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