Department of Molecular and Life Sciences, Hanyang University, Ansan, Republic of Korea.
Department of Neuropsychiatry, College of Medicine and Institute of Mental Health, Hanyang University, Seoul, Republic of Korea.
Psychiatry Investig. 2015 Jan;12(1):81-91. doi: 10.4306/pi.2015.12.1.81. Epub 2015 Jan 12.
Antidepressants are known to positively influence several factors in patients with depressive disorders, resulting in increased neurogenesis and subsequent relief of depressive disorders. To study the effects of venlafaxine during neural differentiation at the cellular level, we looked at its effect on protein expression and regulation mechanisms during neural differentiation.
After exposing NCCIT cell-derived EBs to venlafaxine during differentiation (1 day and 7 days), changes in protein expression were analyzed by 2-DE and MALDI-TOF MS analysis. Gene levels of proteins regulated by venlafaxine were analyzed by real-time RT-PCR.
Treatment with venlafaxine decreased expression of prolyl 4-hydroxylase (P4HB), ubiquitin-conjugating enzyme E2K (HIP2) and plastin 3 (T-plastin), and up-regulated expression of growth factor beta-3 (TGF-β3), dihydropyrimidinase-like 3 (DPYSL3), and pyruvate kinase (PKM) after differentiation for 1 and 7 days. In cells exposed to venlafaxine, the mRNA expression patterns of HIP2 and PKM, which function as negative and positive regulators of differentiation and neuronal survival, respectively, were consistent with the observed changes in protein expression.
Our findings may contribute to improve understanding of molecular mechanism of venlafaxine.
抗抑郁药已知可对抑郁障碍患者的多种因素产生积极影响，从而增加神经发生并随后缓解抑郁障碍。为了在细胞水平上研究文拉法辛在神经分化过程中的作用，我们研究了它在神经分化过程中对蛋白质表达和调节机制的影响。
在分化过程中（第 1 天和第 7 天）将 NCCIT 细胞衍生的 EBs 暴露于文拉法辛中，通过 2-DE 和 MALDI-TOF MS 分析来分析蛋白质表达的变化。通过实时 RT-PCR 分析受文拉法辛调节的蛋白质的基因水平。
文拉法辛处理可降低脯氨酰 4-羟化酶（P4HB）、泛素连接酶 E2K（HIP2）和肌动蛋白 3（T-肌动蛋白）的表达，上调生长因子-β3（TGF-β3）、二氢嘧啶酶样 3（DPYSL3）和丙酮酸激酶（PKM）的表达在分化 1 天和 7 天后。在暴露于文拉法辛的细胞中，HIP2 和 PKM 的 mRNA 表达模式分别作为分化和神经元存活的负调节剂和正调节剂，与观察到的蛋白质表达变化一致。
我们的发现可能有助于提高对文拉法辛的分子机制的理解。
