Fluoxetine up-regulates expression of cellular FLICE-inhibitory protein and inhibits LPS-induced apoptosis in hippocampus-derived neural stem cell

Shih Hwa Chiou, Shih Jen Chen, Chi Hsien Peng, Yu Li Chang, Hung Hai Ku, Wen-Ming Hsu, Larry L.T. Ho, Chen Hsen Lee

研究成果: 雜誌貢獻文章同行評審

83 引文 斯高帕斯(Scopus)

摘要

Fluoxetine is a widely used antidepressant compound which inhibits the reuptake of serotonin in the central nervous system. Recent studies have shown that fluoxetine can promote neurogenesis and improve the survival rate of neurons. However, whether fluoxetine modulates the proliferation or neuroprotection effects of neural stem cells (NSCs) needs to be elucidated. In this study, we demonstrated that 20 μM fluoxetine can increase the cell proliferation of NSCs derived from the hippocampus of adult rats by MTT test. The up-regulated expression of Bcl-2, Bcl-xL and the cellular FLICE-inhibitory protein (c-FLIP) in fluoxetine-treated NSCs was detected by real-time RT-PCR. Our results further showed that fluoxetine protects the lipopolysaccharide- induced apoptosis in NSCs, in part, by activating the expression of c-FLIP. Moreover, c-FLIP induction by fluoxetine requires the activation of the c-FLIP promoter region spanning nucleotides -414 to -133, including CREB and SP1 sites. This effect appeared to involve the phosphatidylinositol-3-kinase-dependent pathway. Furthermore, fluoxetine treatment significantly inhibited the induction of proinflammatory factor IL-1β, IL-6, and TNF-α in the culture medium of LPS-treated NSCs (p < 0.01). The results of high performance liquid chromatography coupled to electrochemical detection further confirmed that fluoxentine increased the functional production of serotonin in NSCs. Together, these data demonstrate the specific activation of c-FLIP by fluoxetine and indicate the novel role of fluoxetine for neuroprotection in the treatment of depression.

原文英語
頁(從 - 到)391-400
頁數10
期刊Biochemical and Biophysical Research Communications
343
發行號2
DOIs
出版狀態已發佈 - 5月 5 2006
對外發佈

ASJC Scopus subject areas

  • 生物物理學
  • 生物化學
  • 分子生物學
  • 細胞生物學

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