인간 배아 암세포에서 retinoic acid로 유도된 분화의 초기 단계 동안 벤라팍신에 의해 조절되는 단백질체 분석

Abstract

Venlafaxine, one of serotonin-nerepinephirne reuptake inhibitors, is known to play an important role in cellular mechanisms responsible for neural plasticity including neurogenesis. Neurotransmitter such as serotonin is found in early embryos as well as brain in mammalian. To study the effects of venlafaxine during early retinoic acid (RA) induced differentiation of embryonic bodies (EBs) derived from NCCIT cells, we looked at its effect on protein expression and regulation mechanisms. After exposing NCCIT cell-derived embryonic bodies to venlafaxine during differentiation (1 day and 7 days), changes in protein expression were analyzed by 2-DE and MALDI-TOF MS analysis. 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 survival of cells, respectively, were consistent with the observed changes in protein expression. Our findings may contribute to improve understanding relationship between the embryotoxicity of venlafaxine and its molecular mechanism.