PMID- 10369466 OWN - NLM STAT- MEDLINE DCOM- 19990901 LR - 20181113 IS - 0007-1188 (Print) IS - 0007-1188 (Linking) VI - 127 IP - 1 DP - 1999 May TI - Effect of the neuroprotective compound SR57746A on nerve growth factor synthesis in cultured astrocytes from neonatal rat cortex. PG - 139-44 AB - The neurotrophic factor promoting activity of the neuroprotective compound SR57746A was evaluated in primary cultures of neonatal rat cortical astrocytes by studying the synthesis of nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF). A concentration- and time-dependent increase of nerve growth factor mRNA was induced by SR57746A (10 nM-1 microM). In these astrocytes, BDNF mRNA contents were increased to a significant but smaller extent, and beta-actin mRNA showed no variation. SR57746A (1 microM) induced increases of both de novo protein translation after 6 h of incubation and NGF release into the extracellular medium after 6-24 h. These effects were preceded by a transient augmentation of junB, c-fos and c-jun mRNA contents. These increases of AP-1 family mRNA were associated with increased nuclear AP-1 binding activity. The results show that SR57746A can increase the synthesis and release of NGF in rat cortical astrocytes. Such effects may contribute to the drug's previously described neuroprotective effects. FAU - Labie, C AU - Labie C AD - Department of Neuropsychiatry Research, Sanofi Recherche, Toulouse, France. christophe.labie@sanofi.com FAU - Lafon, C AU - Lafon C FAU - Marmouget, C AU - Marmouget C FAU - Saubusse, P AU - Saubusse P FAU - Fournier, J AU - Fournier J FAU - Keane, P E AU - Keane PE FAU - Le Fur, G AU - Le Fur G FAU - Soubrie, P AU - Soubrie P LA - eng PT - Journal Article PL - England TA - Br J Pharmacol JT - British journal of pharmacology JID - 7502536 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Naphthalenes) RN - 0 (Nerve Growth Factors) RN - 0 (Neuroprotective Agents) RN - 0 (Pyridines) RN - 0 (RNA, Messenger) RN - 0 (Transcription Factor AP-1) RN - EC 3.1.30.1 (Single-Strand Specific DNA and RNA Endonucleases) RN - V8QL94KNQO (xaliproden) SB - IM MH - Animals MH - Animals, Newborn MH - Astrocytes/drug effects/*metabolism MH - Brain-Derived Neurotrophic Factor/biosynthesis/genetics MH - Cells, Cultured MH - Cerebral Cortex/cytology/drug effects/*metabolism MH - Enzyme-Linked Immunosorbent Assay MH - Naphthalenes/*pharmacology MH - Nerve Growth Factors/*biosynthesis/genetics MH - Neuroprotective Agents/*pharmacology MH - Precipitin Tests MH - Protein Biosynthesis MH - Pyridines/*pharmacology MH - RNA, Messenger/biosynthesis MH - Rats MH - Rats, Sprague-Dawley MH - Single-Strand Specific DNA and RNA Endonucleases/metabolism MH - Transcription Factor AP-1/metabolism PMC - PMC1566010 EDAT- 1999/06/16 00:00 MHDA- 1999/06/16 00:01 PMCR- 2000/05/01 CRDT- 1999/06/16 00:00 PHST- 1999/06/16 00:00 [pubmed] PHST- 1999/06/16 00:01 [medline] PHST- 1999/06/16 00:00 [entrez] PHST- 2000/05/01 00:00 [pmc-release] AID - 0702545 [pii] AID - 10.1038/sj.bjp.0702545 [doi] PST - ppublish SO - Br J Pharmacol. 1999 May;127(1):139-44. doi: 10.1038/sj.bjp.0702545.