Bai Qiufang, Song Dan, Gu Li, Verkhratsky Alexei, Peng Liang
Laboratory of Metabolic Brain Diseases, Institute of Metabolic Disease Research and Drug Development, China Medical University, No. 77, Puhe Road, Shenbei District, Shenyang, People's Republic of China.
Faculty of Life Science, The University of Manchester, Manchester, UK.
Psychopharmacology (Berl). 2017 Apr;234(7):1069-1077. doi: 10.1007/s00213-017-4547-3. Epub 2017 Feb 24.
Here, we present the data indicating that chronic treatment with fluoxetine regulates Cav-1/PTEN/PI3K/AKT/GSK-3β signalling pathway and glycogen content in primary cultures of astrocytes with bi-phasic concentration dependence.
At lower concentrations, fluoxetine downregulates gene expression of Cav-1, decreases membrane content of PTEN, increases activity of PI3K/AKT, and elevates GSK-3β phosphorylation thus suppressing its activity. At higher concentrations, fluoxetine acts in an inverse fashion. As expected, fluoxetine at lower concentrations increased while at higher concentrations decreased glycogen content in astrocytes.
Our findings indicate that bi-phasic regulation of glycogen content via Cav-1/PTEN/PI3K/AKT/GSK-3β pathway by fluoxetine may be responsible for both therapeutic and side effects of the drug.
在此，我们展示的数据表明，用氟西汀进行长期治疗可调节原代星形胶质细胞培养物中Cav-1/PTEN/PI3K/AKT/GSK-3β信号通路和糖原含量，且具有双相浓度依赖性。
在较低浓度下，氟西汀下调Cav-1的基因表达，降低PTEN的膜含量，增加PI3K/AKT的活性，并提高GSK-3β的磷酸化水平，从而抑制其活性。在较高浓度下，氟西汀的作用方式相反。正如预期的那样，较低浓度的氟西汀可增加星形胶质细胞中的糖原含量，而较高浓度则会降低糖原含量。
我们的研究结果表明，氟西汀通过Cav-1/PTEN/PI3K/AKT/GSK-3β途径对糖原含量进行双相调节，可能是该药物治疗作用和副作用的原因。
