Molecular Mechanism of bFGF-induced Bcl-2 expression in Hippocampal Neuronal Progenitors ( H19-7 cells)

Abstract

Bcl-2 has been known as an anti-apoptotic protein including Bcl-XL and Bcl-W. Apart from this function, some studies that Bcl-2 promotes axonal growth has been reported. Expressed Bcl-2 seems function differently depending on types of cells and signal molecules. Exogenous bFGF(bFGF-2) is commonly used to proliferate neural stem cells and progenitor cells in vitro. In present study, we investigated the signaling pathway leading to Bcl-2 expression in response to bFGF in H19-7 cells, hippocampal progenitor cells. In addition, it was examined whether bFGF-induced Bcl-2 expression has a role in neurite outgrowing. Our data show that U73122 (PI-PLCγ inhibitor) and DNRas (dominent negative form of Ras) reduced Bcl-2 expression independently, indicating that bFGF-induced Bcl-2 expression was influenced by PLCγ or Ras activation. We also examined whether PI3K is a downstream effector of PLCγ or Ras. PLCγ and Ras signaling were converged into PI3K signaling molecule. Next, We found that JNK and ERK were downstream molecules of PI3Kinase in bFGF-induced Bcl-2 expression by using LY294002(PI3K inhibitor). Besides, we also found that a transcription factor, STAT3 might be related to Bcl-2 expression through PLCγ or Ras signaling pathway. In conclusion, our data suggest that three signaling pathways are involved in increased expression of Bcl-2 in response to bFGF, those are PLCγ/ PI3K/ JNK/ STAT3 (Ser727), Ras/ PI3K/ JNK / STAT3 (Ser727,Tyr705), and PI3K/ ERK/ STAT3 (Ser727), respectively. Moreover, these data support that bFGF-induced Bcl-2 expression has a role in neuronal differentiation of H19-7 cells.