PMID- 16682819 OWN - NLM STAT- MEDLINE DCOM- 20070206 LR - 20240315 IS - 1016-8478 (Print) IS - 1016-8478 (Linking) VI - 21 IP - 2 DP - 2006 Apr 30 TI - Nerve growth factor activates brain-derived neurotrophic factor promoter IV via extracellular signal-regulated protein kinase 1/2 in PC12 cells. PG - 237-43 AB - Brain-derived neurotrophic factor (BDNF) is a neuromodulator of nociceptive responses in the dorsal root ganglia (DRG) and spinal cord. BDNF synthesis increases in response to nerve growth factor (NGF) in trkA-expressing small and medium-sized DRG neurons after inflammation. Previously we demonstrated differential activation of multiple BDNF promoters in the DRG following peripheral nerve injury and inflammation. Using reporter constructs containing individual promoter regions, we investigated the effect of NGF on the multiple BDNF promoters, and the signaling pathway by which NGF activates these promoters in PC12 cells. Although all the promoters were activated 2.4-7.1-fold by NGF treatment, promoter IV gave the greatest induction. The p38 mitogen-activated protein kinase (MAPK) inhibitor, SB203580, phosphatidylinositol 3-kinase (PI-3K) inhibitor, LY294003, protein kinase A (PKA) inhibitor, H89, and protein kinase C (PKC) inhibitor, chelerythrine, had no effect on activation of promoter IV by NGF. However, activation was completely abolished by the MAPK kinase (MEK) inhibitors, U0126 and PD98059. In addition, these inhibitors blocked NGF-induced phosphorylation of extracellular signal-regulated protein kinase (ERK) 1/2. Taken together, these results suggest that the ERK1/2 pathway activates BDNF promoter IV in response to NGF independently of NGF-activated signaling pathways involving PKA and PKC. FAU - Park, So Yun AU - Park SY AD - Department of Anatomy, School of Medicine, Kyungpook National University, Daegu 700-422, Korea. FAU - Lee, Ji Yun AU - Lee JY FAU - Choi, Jun Young AU - Choi JY FAU - Park, Mae Ja AU - Park MJ FAU - Kim, Dong Sun AU - Kim DS LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Mol Cells JT - Molecules and cells JID - 9610936 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Butadienes) RN - 0 (Enzyme Inhibitors) RN - 0 (Flavonoids) RN - 0 (Nitriles) RN - 0 (U 0126) RN - 9061-61-4 (Nerve Growth Factor) RN - EC 2.7.11.11 (Cyclic AMP-Dependent Protein Kinases) RN - EC 2.7.11.13 (Protein Kinase C) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 1) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3) RN - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases) RN - EC 2.7.12.2 (Mitogen-Activated Protein Kinase Kinases) RN - SJE1IO5E3I (2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one) SB - IM MH - Animals MH - *Brain-Derived Neurotrophic Factor/genetics/metabolism MH - Butadienes/metabolism MH - Cyclic AMP-Dependent Protein Kinases/metabolism MH - Enzyme Inhibitors/metabolism MH - Flavonoids/metabolism MH - Genes, Reporter MH - Mitogen-Activated Protein Kinase 1/genetics/*metabolism MH - Mitogen-Activated Protein Kinase 3/genetics/*metabolism MH - Mitogen-Activated Protein Kinase Kinases/antagonists & inhibitors/metabolism MH - Nerve Growth Factor/*metabolism MH - Nitriles/metabolism MH - PC12 Cells MH - *Promoter Regions, Genetic MH - Protein Kinase C/metabolism MH - Rats MH - Signal Transduction/physiology MH - p38 Mitogen-Activated Protein Kinases/antagonists & inhibitors/metabolism EDAT- 2006/05/10 09:00 MHDA- 2007/02/07 09:00 CRDT- 2006/05/10 09:00 PHST- 2006/05/10 09:00 [pubmed] PHST- 2007/02/07 09:00 [medline] PHST- 2006/05/10 09:00 [entrez] AID - S1016-8478(23)12886-X [pii] PST - ppublish SO - Mol Cells. 2006 Apr 30;21(2):237-43.