Fluoxetine upregulates phosphorylated-AKT and phosphorylated-ERK1/2 proteins in neural stem cells: evidence for a crosstalk between AKT and ERK1/2 pathways.
Fluoxetine is a widely used antidepressant drug which inhibits the reuptake of serotonin in the central nervous system (CNS). Recent studies have shown that fluoxetine can promote neurogenesis and improve the survival rate of neurons. However, whether fluoxetine modulates the neuroprotection of neural stem cells (NSCs) needs to be elucidated. In this study, we demonstrated that 50 μM fluoxetine significantly upregulated expression of the phosphorylated-AKT and ERK1/2 proteins in NSCs derived from rats. Besides, expression of phosphorylated-AKT and phosphorylated-ERK1/2 in fluoxetine-treated NSCs was effectively blocked (P<0.05) by both PI3-K inhibitor (LY294002) and MEK inhibitor (PD98059). It was, therefore, concluded that the crosstalk between PI3K/AKT and MAPK/ERK pathways involved AKT and ERK1/2 phosphorylation by fluoxetine treatment. This study points to a novel role of fluoxetine in neuroprotection as an antidepressant drug and also unravels the crosstalk mechanism between the two signaling pathways.
Department of Neurology, Xinqiao Hospital, Third Military Medical University, Chongqing, China.
Wen
W
Huang
Yu
Y
Zhao
Xiaofeng
X
Zhu
Zhiyou
Z
Cai
Shijun
S
Wang
Shengtao
S
Yao
Zhiguo
Z
Qi
Peng
P
Xie
D000818:Animals; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005473:Fluoxetine / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D020935:MAP Kinase Signaling System; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000235:genetics / Q000378:metabolism; D058953:Neural Stem Cells / Q000201:enzymology*; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects*
D048049:Extracellular Signal-Regulated MAP Kinases; D005473:Fluoxetine; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D047428:Protein Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt; D017367:Selective Serotonin Reuptake Inhibitors