Metabolomics-based discovery of a metabolite that enhances oligodendrocyte maturation.
Metabolomics-based discovery of a metabolite that enhances oligodendrocyte maturation.
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DOI：
10.1038/nchembio.2517
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发表时间：
2018-01
影响因子：
14.8
通讯作者：
Lairson LL
中科院分区：
文献类型：
--
作者：
Beyer BA;Fang M;Sadrian B;Montenegro-Burke JR;Plaisted WC;Kok BPC;Saez E;Kondo T;Siuzdak G;Lairson LL
内源性代谢产物在细胞特性和活性的调节中起重要作用。在这里，我们已经调查了少突胶质细胞前体细胞（OPC）分化的过程中，一个过程，成为限制在进行性阶段的脱髓鞘疾病，包括多发性硬化症，使用质谱代谢组学。牛磺酸是一种具有多向生物活性和广泛组织分布特性的氨基磺酸，在少突胶质细胞分化和成熟过程中，牛磺酸的水平显著升高（约20倍）。当以生理相关浓度外源性添加时，发现牛磺酸显著增强药物诱导的体外OPC分化和成熟的过程。作用机制研究表明，牛磺酸的少突胶质细胞分化增强活性主要是由其直接增加可用丝氨酸库的能力驱动的，丝氨酸库作为定义功能性少突胶质细胞状态的髓鞘的鞘糖脂组分合成所需的初始构建单元。
Endogenous metabolites play essential roles in the regulation of cellular identity and activity. Here we have investigated the process of oligodendrocyte precursor cell (OPC) differentiation, a process that becomes limiting during progressive stages of demyelinating diseases, including multiple sclerosis, using mass-spectrometry-based metabolomics. Levels of taurine, an aminosulfonic acid possessing pleotropic biological activities and broad tissue distribution properties, were found to be significantly elevated (~20-fold) during the course of oligodendrocyte differentiation and maturation. When added exogenously at physiologically relevant concentrations, taurine was found to dramatically enhance the processes of drug-induced in vitro OPC differentiation and maturation. Mechanism of action studies suggest that the oligodendrocyte-differentiation-enhancing activities of taurine are driven primarily by its ability to directly increase available serine pools, which serve as the initial building block required for the synthesis of the glycosphingolipid components of myelin that define the functional oligodendrocyte cell state.
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影响因子：
6.2
作者：
Diemel, LT;Wolswijk, G;Cuzner, ML
通讯作者：
Cuzner, ML
影响因子：
48
作者：
Huan T;Forsberg EM;Rinehart D;Johnson CH;Ivanisevic J;Benton HP;Fang M;Aisporna A;Hilmers B;Poole FL;Thorgersen MP;Adams MWW;Krantz G;Fields MW;Robbins PD;Niedernhofer LJ;Ideker T;Majumder EL;Wall JD;Rattray NJW;Goodacre R;Lairson LL;Siuzdak G
通讯作者：
Siuzdak G
DOI：
10.1038/nrm3772
发表时间：
2014-04
期刊：
Nature reviews. Molecular cell biology
影响因子：
--
作者：
通讯作者：
--
影响因子：
158.5
作者：
Chang, A;Tourtellotte, WW;Trapp, BD
通讯作者：
Trapp, BD
影响因子：
29
作者：
Folmes CD;Nelson TJ;Martinez-Fernandez A;Arrell DK;Lindor JZ;Dzeja PP;Ikeda Y;Perez-Terzic C;Terzic A
通讯作者：
Terzic A