Control of Muscle Differentiation by a Mitochondria-Targeted Fluorophore
Control of Muscle Differentiation by a Mitochondria-Targeted Fluorophore
复制标题
DOI：
10.1021/ja906862g
复制
发表时间：
2010-01-20
影响因子：
15
通讯作者：
Chang, Young-Tae
中科院分区：
文献类型：
--
作者：
Kim, Yun Kyung;Ha, Hyung-Ho;Chang, Young-Tae
在肌肉分化过程中，线粒体的形态和分布发生了巨大的变化，为更高的能量消耗率做准备。通过在C2 C12肌发生中应用靶向于C2 C12的玫瑰胺文库，我们发现了一种控制肌肉分化的化合物。当处理未分化的成肌细胞时，我们选择的化合物B25抑制肌管形成，当处理完全分化的肌管时，它诱导多核肌管分裂成单核片段。与已知通过使微管不稳定来诱导肌管分裂的myoseverin相比，B25既不影响微管稳定性也不影响细胞周期。进一步的研究表明，B25通过激活NF-κ B B诱导肌管分裂，NF-κ B是与骨骼肌分化相关的重要信号通路之一。到目前为止，小分子荧光团的使用局限于标记剂或传感器的发现。除了它们作为传感器的潜力之外，在这里我们还展示了荧光小分子在发现诱导特定细胞反应的生物活性探针中的应用。
During muscle differentiation, mitochondria undergo dramatic changes in their morphology and distribution to prepare for the higher rate of energy consumption. By applying a mitochondria-targeted rosamine library in C2C12 myogenesis, we discovered one compound that controls muscle differentiation. When treated to undifferentiated myoblasts, our selected compound, B25, inhibited myotube formation, and when treated to fully differentiated myotubes, it induced fission of multinucleated myotubes into mononucleated fragments. Compared to myoseverin, which is known for inducing myotube fission by destabilizing microtubules, B25 affects neither microtubule stability nor cell cycle. Further investigation identified that B25 induces myotube fission through the activation of NF-kappa B, which is one of the important signaling pathways linked to skeletal muscle differentiation. So far, the use of small-molecule fluorophores is limited in the discovery of labeling agents or sensors. In addition to their potential as a sensor, here we show the application of fluorescent small molecules in the discovery of a bioactive probe that induces a specific cellular response.