Beyer Brittney A, Fang Mingliang, Sadrian Benjamin, Montenegro-Burke J Rafael, Plaisted Warren C, Kok Bernard P C, Saez Enrique, Kondo Toru, Siuzdak Gary, Lairson Luke L
Department of Chemistry, The Scripps Research Institute, La Jolla, California, USA.
The California Institute for Biomedical Research, La Jolla, California, USA.
Nat Chem Biol. 2018 Jan;14(1):22-28. doi: 10.1038/nchembio.2517. Epub 2017 Nov 13.
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.
内源性代谢物在细胞特性和活性的调节中发挥着重要作用。在此，我们利用基于质谱的代谢组学技术，研究了少突胶质前体细胞（OPC）的分化过程，该过程在包括多发性硬化症在内的脱髓鞘疾病的进展阶段会成为限制因素。发现牛磺酸（一种具有多效生物活性和广泛组织分布特性的氨基磺酸）的水平在少突胶质细胞分化和成熟过程中显著升高（约20倍）。当以生理相关浓度外源添加时，发现牛磺酸能显著增强药物诱导的体外OPC分化和成熟过程。作用机制研究表明，牛磺酸增强少突胶质细胞分化的活性主要是由其直接增加可用丝氨酸池的能力驱动的，丝氨酸是合成定义功能性少突胶质细胞状态的髓鞘糖脂成分所需的初始构建块。
