Targeted Approach to Distinguish and Determine Absolute Levels of GDF8 and GDF11 in Mouse Serum
Targeted Approach to Distinguish and Determine Absolute Levels of GDF8 and GDF11 in Mouse Serum
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DOI：
10.1002/pmic.201900104
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发表时间：
2020-05-13
期刊：
影响因子：
3.4
通讯作者：
Shevchuk, Olga
中科院分区：
文献类型：
--
作者：
Camparini, Luca;Kollipara, Laxmikanth;Shevchuk, Olga
生长分化因子11(GDF11)是一种调节啮齿动物心肌细胞大小的转化生长因子-β超家族循环因子，其活性区域的氨基酸序列与骨骼肌块的主要决定因素肌肉抑制素(GDF8)有90%的氨基酸序列同源性。关于血液循环水平与年龄有关的变化的数据相互矛盾，主要是由于缺乏具体的检测方法。最近，基于LC-MS/MS的分析表明，循环中GDF11的水平在人类一生中没有显著变化，但男性的GDF8水平随着年龄的增长而下降。本文提出了一种基于平行反应监测的LC-MS/MS联用技术结合免疫沉淀的检测方法，可以可靠地区分GDF11和GDF8，并测定它们在小鼠血清中的内源性水平。这些数据表明，雌性小鼠的GDF11和GDF8循环水平都随着年龄的增长而显著下降。
Growth differentiation factor 11 (GDF11) is a TGF-beta superfamily circulating factor that regulates cardiomyocyte size in rodents, sharing 90% amino acid sequence identity in the active domains with myostatin (GDF8)-the major determinant of skeletal muscle mass. Conflicting data on age-related changes in circulating levels have been reported mainly due to the lack of specific detection methods. More recently, liquid chromatography tandem mass spectrometry (LC-MS/MS) based assay showed that the circulating levels of GDF11 do not change significantly throughout human lifespan, but GDF8 levels decrease with aging in men. Here a novel detection method is demonstrated based on parallel reaction monitoring LC-MS/MS assay combined with immunoprecipitation to reliably distinguish GDF11 and GDF8 as well as determine their endogenous levels in mouse serum. The data indicate that both GDF11 and GDF8 circulating levels significantly decline with aging in female mice.