Fluoxetine-induced up-regulation of 14-3-3zeta and tryptophan hydroxylase levels in RBL-2H3 cells.
The primary mechanisms of antidepressants are based on the monoamine depletion hypothesis. However, we do not yet know the full cascade of mechanisms responsible for the therapeutic effect of antidepressants. To identify the genes involved in the therapeutic mechanism of the selective serotonin reuptake inhibitor, fluoxetine, we used a cDNA microarray analysis with RBL-2H3 cells. We observed the transcriptional changes of several tens of genes containing the 14-3-3zeta gene in the fluoxetine-treated RBL-2H3 cells. Real-time RT-PCR and Western blotting confirmed changes in the expression of the gene and protein. The increase of 14-3-3zeta mRNA was observed at 72 h in the fluoxetine-treated RBL-2H3 cells. The increase of 14-3-3zeta protein was observed at 48 and 72 h. In this study, the expressions of the 14-3-3zeta gene and the protein were up-regulated at 72 h. In addition, the increase of TPH mRNA was observed at 12, 24 and 72 h in the fluoxetine-treated RBL-2H3 cells. We conclude that fluoxetine induces increases of 14-3-3zeta mRNA, 14-3-3zeta protein and TPH mRNA at 72 h in the RBL-2H3 cells. This suggests that the 14-3-3zeta and TPH genes may play a role in the molecular mechanism of fluoxetine. To date, no cases of 14-3-3zeta alterations by antidepressants and specifically by fluoxetine have been reported.
Baik
Seung-Youn
SY
Department of Biochemistry, Division of Molecular and Life Sciences, Hanyang University, Ansan 426-791, Republic of Korea.
Jung
Kyoung Hwa
KH
Choi
Mi-Ran
MR
Yang
Byung-Hwan
BH
Kim
Seok-Hyeon
SH
Lee
Jun-Suk
JS
Oh
Dong-Yul
DY
Choi
Ihn-Geun
IG
Chung
Hesson
H
Chai
Young Gyu
YG
D048948:14-3-3 Proteins / Q000378:metabolism*; D000818:Animals; D018687:Antidepressive Agents, Second-Generation / Q000494:pharmacology; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D005473:Fluoxetine / Q000494:pharmacology*; D015471:Leukemia, Basophilic, Acute / Q000378:metabolism*; D051381:Rats; D014365:Tryptophan Hydroxylase / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects
D048948:14-3-3 Proteins; D018687:Antidepressive Agents, Second-Generation; D005473:Fluoxetine; D014365:Tryptophan Hydroxylase