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Serotonin (5‐HT) induces glial cell line‐derived neurotrophic factor (GDNF) mRNA expression via the transactivation of fibroblast growth factor receptor 2 (FGFR2) in rat C6 glioma cells
Author(s) -
Tsuchioka Mami,
Takebayashi Minoru,
Hisaoka Kazue,
Maeda Natsuko,
Nakata Yoshihiro
Publication year - 2008
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2008.05357.x
Subject(s) - glial cell line derived neurotrophic factor , gdnf family of ligands , mapk/erk pathway , fibroblast growth factor receptor 1 , transactivation , biology , receptor tyrosine kinase , microbiology and biotechnology , neurotrophic factors , basic fibroblast growth factor , fibroblast growth factor receptor , chemistry , cancer research , phosphorylation , fibroblast growth factor , growth factor , receptor , biochemistry , gene expression , gene
We previously reported that serotonin (5‐HT) increased glial cell line‐derived neurotrophic factor (GDNF) release in a 5‐HT 2 receptor (5‐HT 2 R) and mitogen‐activated protein kinase kinase/extracellular signal‐related kinase (MEK/ERK)‐dependent manner in rat C6 glioma cells (C6 cells), a model of astrocytes. We herein found that 5‐HT‐induced rapid ERK phosphorylation was blocked by 5‐HT 2 R antagonists in C6 cells. We therefore examined 5‐HT‐induced ERK phosphorylation to reveal the mechanism of 5‐HT‐induced GDNF mRNA expression. As 5‐HT‐induced ERK phosphorylation was blocked by inhibitors for Gα q/11 and fibroblast growth factor receptor (FGFR), but not for second messengers downstream of Gα q/11 , 5‐HT 2 R‐mediated FGFR transactivation was suggested to be involved in the ERK phosphorylation. Although FGFR1 and 2 were functionally expressed in C6 cells, 5‐HT selectively phosphorylated FGFR2. Indeed, small interfering RNA for FGFR2, but not for FGFR1, blocked 5‐HT‐induced ERK phosphorylation. As Src family tyrosine kinase inhibitors and microtubule depolymerizing agents blocked 5‐HT‐induced FGFR2 phosphorylation, Src family tyrosine kinase and stabilized microtubules were suggested to act upstream of FGFR2. Finally, 5‐HT‐induced GDNF mRNA expression was also inhibited by the blockade of 5‐HT 2 R, FGFR, and Src family tyrosine kinase. In conclusion, our findings suggest that 5‐HT induces GDNF mRNA expression via 5‐HT 2 R‐mediated FGFR2 transactivation in C6 cells.