Liang Guoying, Cline Gary W, Macica Carolyn M
Division of Endocrinology, Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06520-8020, USA.
Glia. 2007 Apr 15;55(6):632-41. doi: 10.1002/glia.20496.
Schwann cell (SC) differentiation to the myelinating phenotype is characterized by the elaboration of a lipid-rich membrane and the expression of myelin-specific proteins. Insulin-like growth factor-1 (IGF-1) has been identified as a growth factor that stimulates the early events of myelination in SCs that signals via the PI3K/Akt pathway. Given the role of IGF-1 in promoting myelination, we performed studies to determine if the fatty acid biosynthetic pathway was a target of IGF-1 signaling in the formation of myelin membrane in dorsal root ganglion neuron/Schwann cell (DRG/SC) cocultures. We report that the fatty acid profile of lipid extracts of cocultures treated with IGF-1 match that reported for native myelin membrane by electrospray mass spectroscopy analysis. We also demonstrate de novo fatty acid biosynthesis in response to IGF-1 treatment in DRG/SC cocultures metabolically labeled with (13)C-acetate as a carbon source for fatty acid synthesis. Consistent with this finding, Western blot analysis of lysates from both cocultures and purified SCs reveal that IGF-1 stimulates two key fatty acid synthesizing enzymes. Additionally, we show that stimulation of fatty acid synthesizing enzymes is mediated by the PI3K/Akt signaling pathway. We also show that the fatty acid synthesizing enzymes and associated signaling pathways are elevated during the period of myelin membrane formation in sciatic nerve. Collectively, these findings demonstrate that IGF-1 plays an important regulatory function during myelin membrane formation.
雪旺细胞（SC）向髓鞘形成表型的分化特征在于富含脂质的膜的形成以及髓鞘特异性蛋白的表达。胰岛素样生长因子-1（IGF-1）已被确定为一种生长因子，它能刺激雪旺细胞中髓鞘形成的早期事件，并通过PI3K/Akt信号通路进行信号传导。鉴于IGF-1在促进髓鞘形成中的作用，我们进行了研究，以确定脂肪酸生物合成途径是否是背根神经节神经元/雪旺细胞（DRG/SC）共培养物中IGF-1信号传导在髓鞘膜形成过程中的作用靶点。我们报告称，经IGF-1处理的共培养物脂质提取物的脂肪酸谱，通过电喷雾质谱分析与天然髓鞘膜的脂肪酸谱相匹配。我们还证明，在用（13）C-乙酸盐作为脂肪酸合成碳源进行代谢标记的DRG/SC共培养物中，对IGF-1处理有脂肪酸的从头合成。与此发现一致，对共培养物和纯化雪旺细胞的裂解物进行的蛋白质印迹分析表明，IGF-1刺激两种关键的脂肪酸合成酶。此外，我们表明脂肪酸合成酶的刺激是由PI3K/Akt信号通路介导的。我们还表明，在坐骨神经髓鞘膜形成期间，脂肪酸合成酶和相关信号通路会升高。总的来说，这些发现表明IGF-1在髓鞘膜形成过程中发挥着重要的调节功能。
