Igment Epithelium-derived Factor Induces Pro-survival Enes through Cyclic Amp-responsive Element Binding Rotein and Nuclear Factor Kappa B Activation in Rat Ultured Cerebellar Granule Cells: Implication for Its Europrotective Effect

bstract—Pigment epithelium-derived factor (PEDF) protects mmature cerebellar granule cell neurons (CGCs) against apotosis induced by K and serum deprivation. However, the recise mechanism of this protection remains unknown. We ecently reported that the transcription factor nuclear factor appa B (NFB) is activated in PEDF-treated CGCs. Although it s well known that NFB blocks apoptotic cell death through he induction of pro-survival factors, the effects of PEDF on the xpression of these factors are not fully understood. In this tudy, we employed the use of reverse transcriptase–polymerse chain reaction to analyze the gene expression of certain ro-survival genes and found that genes such as c-IAP1, cAP2, FLIPs, A1/Bfl-1 and Mn-SOD were induced in PEDFreated neurons. On the other hand, no induction was observed f the pro-apoptotic Bcl-2 family members Bax and Bid at any ime from 3 to 24 h following PEDF addition. Furthermore, phoshorylation of cyclic AMP-responsive element binding protein CREB) and increment of nuclear cyclic AMP-response element CRE)-like DNA binding were observed in PEDF-treated CGCs. he anti-apoptotic effect of PEDF was blocked by overexpresion of dominant negative CREB or a mutated form of I B . hese results suggested that induction of both CREand NFB-dependent genes is required for the observed neuroprotecive effects of PEDF on CGCs. © 2005 Published by Elsevier Ltd n behalf of IBRO.