bFGF inhibits the activation of caspase-3 and apoptosis of P19 embryonal carcinoma cells during neuronal differentiation

Abstract

P19 embryonal carcinoma (EC) cells undergo apoptosis during neuronal differentiation induced by all-trans retinoic acid (RA). Caspase-3-like proteases are activated and involved in the apoptosis of P19 EC cells during neuronal differentiation. 1 Recently it has been shown that growth factor signals protect against apoptosis by phosphorylation of Bad. Phosphorylated Bad, an apoptotic member of the Bcl-2 family, cannot bind to Bcl-x L and results in Bcl-x L homodimer formation and subsequent antiapoptotic activity. In the present study, we demonstrate that this system is used generally to protect against apoptosis during neuronal differentiation. Bcl-x L inhibited the activation of caspase-3-like proteases. Basic fibroblast growth factor (bFGF) inhibited more than 90% of the caspase-3-like activity, inhibited processing of caspase-3 into its active form, and inhibited DNA fragmentation. bFGF activated phosphatidyl-inositol-3-kinase (PI3K) and stimulated the phosphorylation of Bad. Phosphorylation was inhibited by wortmannin, an inhibitor of PI3K and its downstream target Akt. Thus, Bad is a target of the FGF receptor-mediated signals involved in the protection against activation of caspase-3.

Expression of Selected Apoptosis Related Genes, MIF, IGIF and TNF.ALPHA., during Retinoic Acid-Induced Neural Differentiation in Murine Embryonic Stem Cells.

“…We have noted that apoptosis during retinoic acid-induced ES differ- entiation was accompanied by increased expression of effector caspases 3 and 6. It has been reported previously that retinoic acid can induce activation of caspase-3 and cause apoptosis during neural differentiation of P19 embryonal carcinoma cells and can be prevented by bFGF (Miho et al, 1999). We have found significant increased in caspase 6, as well as caspase 3 during ES neural differentiation.…”

Fibroblast growth factor 2 up regulates telomerase activity in neural precursor cells

“…Akt is one of the down stream targets of phosphatidylinositol 3-kinase (PI3-K) that is a signaling molecule associated with receptors of growth factors (Datta et al, 1996). PI3-K/Akt pathway has been shown to be involved in the intracellular signaling of FGF2 in cells of neural origin (Miho et al, 1999;van Weering et al, 1998) and thus should be proposed to mediate the FGF-2-induced telomerase upregulation. The role of this pathway in telomerase regulation is also sustained by studies involving PTEN, an antioncogene that exerts its role as a tumor suppressor by negatively regulating the Akt signaling pathway (Stambolic et al, 1998).…”

Low-Density Lipoprotein in Hypercholesterolemic Human Plasma Induces Vascular Endothelial Cell Apoptosis by Inhibiting Fibroblast Growth Factor 2 Transcription

“…When added to a variety of cell types, FGF-2 stimulates phosphoinositol-3-kinase (PI3K), which in turn activates Akt (protein kinase B). 29 Akt inhibits apoptosis by deactivating downstream targets such as BAD and forkhead transcription factor. 29,30 We previously showed that Cu 2ϩ -oxLDL downregulates endothelial FGF-2 by increasing posttranscriptional destabilization.…”

“…29 Akt inhibits apoptosis by deactivating downstream targets such as BAD and forkhead transcription factor. 29,30 We previously showed that Cu 2ϩ -oxLDL downregulates endothelial FGF-2 by increasing posttranscriptional destabilization. 22 After pretreatment with rPAF-AH, L 5 lost the ability to inhibit FGF-2 transcription and was no longer proapoptotic.…”