Fluoxetine-induced regulation of heat shock protein 90 and 14-3-3ε in human embryonic carcinoma cells.

ABSTRACT

Fluoxetine, a serotonin-selective reuptake inhibitor, exerts antidepressant and antianxiety effects on major depressive and anxiety disorders. Previous studies suggest that treatment with fluoxetine influences the expression of various proteins that are involved in proliferation, differentiation, and apoptosis in the neuronal cells of the brain. However, many aspects of the molecular pathways that modulate antidepressant action are not well understood. Here, with the aim of identifying proteins involved in antidepressant action, we examined the protein expression profile of human embryonic carcinoma (NCCIT) cells in response to fluoxetine treatment using proteomic techniques such as two-dimensional gel electrophoresis and matrix-assisted laser desorption ionization-time-of-flight mass spectrometry (MALDI-TOF MS). We found several upregulated and downregulated proteins in fluoxetine-treated NCCIT cells, and then biochemically confirmed the increased expression of heat shock protein 90 and 14-3-3ε, which play an essential role in many cellular mechanisms including cell cycle control and other signaling pathways. Our data suggest that the regulated expression of heat shock protein 90, 14-3-3ε, and other identified proteins may be associated with the therapeutic action of fluoxetine.