Mechanism for Bcl-2 expression induced by bFGF in H19-7cells

초록

Bcl-2 has been known as an anti-apoptotic protein including Bcl-XL and Bcl-W. Recently, it is reported that Bcl-2 control axonal growth has been reported. In spite of many studies about functions of Bcl-2, the molecular mechanism of Bcl-2 expression remains unclear. In this study, we have examined the signaling pathway leading to Bcl-2 expression in response to bFGF in H19-7 cells, hippocampal progenitor cells. First, it was investigated whether bFGF treatment induces Bcl-2 over-expression in H19-7 cells. Based on our previous report that PLCγ is activated by bFGF, we studied whether PLCγ and p85 of PI3K subunits were translocated to the membrane and tried to inhibit PLCγ or PI3K activity to find whether PLCγ or PI3K regulates Bcl-2 expression by introducing U73122 or LY294002. Our data shows that the inhibition of PLCγ or PI3K reduces Bcl-2 expression significantly. Second, we investigated whether PI3K was down-regulated by the treatment of U73122, PLCγ inhibitor. In addition, the effects of Ca2+chelator, Bapta-am on Bcl-2 expression was studied because IP3, the end product of PLCγ leads to Ca2+ release from ER (endoplasmic recticulum). We also observed that the phosphorylation of JNK was inhibited by Bapta-am, or U73122 or LY294002, which resulted in decreasing of Bcl-2 expression. Third, we examined that a transcription factor, STAT3 (ser727) was related with Bcl-2 expression through PLCγ, PI3K, and JNK activation. We also studied whether a small G protein, Ras was involved in Bcl-2 expression. In this study, we found that Ras had the effect on Bcl-2 expression through JNK and STAT3 (ser727). In conclusion the expression of Bcl-2 is increased through PLCγ /Ras /PI3K /JNK /STAT3(ser727) or PLCγ/ PI3K /Ras /JNK /STAT3(ser727) in H19-7 cells by bFGF.