PMID- 11494368 OWN - NLM STAT- MEDLINE DCOM- 20010913 LR - 20181130 IS - 0360-4012 (Print) IS - 0360-4012 (Linking) VI - 65 IP - 4 DP - 2001 Aug 15 TI - Neurotrophin secretion from cultured microglia. PG - 322-31 AB - Because microglia have been suggested to produce neurotrophins, we tested this ability in vitro. Rat primary microglia were found to constitutively secrete a limited amount of brain-derived neurotrophic factor (BDNF), but nerve growth factor (NGF) and neurotrophin-3 (NT-3) were undetectable in the conditioned medium. Stimulation of the cells with lipopolysaccharide (LPS) increased BDNF secretion, and induced NGF secretion. As a first step to examine this regulation system, the association of protein kinase C (PKC) was pharmacologically analyzed. A PKC activator, phorbol-12-myristate-13-acetate, enhanced the secretion of BDNF. Pre-treatment of microglia with a PKC inhibitor, bisindolylmaleimide, suppressed LPS-stimulated BDNF secretion as well as the constitutive one. These results suggest that the PKC signaling cascade is closely associated with BDNF secretion. Among PKC isoforms, PKCalpha probably plays a role in BDNF secretion, based on the results of experiments using a specific PKC activator, 1-oleoyl-2-acetyl-sn-glycerol, and a specific PKC inhibitor, Go 6976, and by immunoblotting. Taken together, these findings suggest that the secretion of BDNF from microglia is regulated through PKCalpha-associated signal transduction mechanism. CI - Copyright 2001 Wiley-Liss, Inc. FAU - Nakajima, K AU - Nakajima K AD - Institute of Life Science, Soka University, 1-236, Tangi-machi, Hachioji, Tokyo 192-8577. nakajima@t.soka.ac.jp FAU - Honda, S AU - Honda S FAU - Tohyama, Y AU - Tohyama Y FAU - Imai, Y AU - Imai Y FAU - Kohsaka, S AU - Kohsaka S FAU - Kurihara, T AU - Kurihara T LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - J Neurosci Res JT - Journal of neuroscience research JID - 7600111 RN - 0 (Antibodies) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Carbazoles) RN - 0 (Carcinogens) RN - 0 (Culture Media, Conditioned) RN - 0 (Diglycerides) RN - 0 (Enzyme Inhibitors) RN - 0 (Indoles) RN - 0 (Isoenzymes) RN - 0 (Lipopolysaccharides) RN - 0 (Maleimides) RN - 0 (Nerve Growth Factors) RN - 0 (Neurotrophin 3) RN - 136194-77-9 (Go 6976) RN - 86390-77-4 (1-oleoyl-2-acetylglycerol) RN - 9061-61-4 (Nerve Growth Factor) RN - EC 2.7.11.13 (Protein Kinase C) RN - EC 2.7.11.13 (Protein Kinase C-alpha) RN - MBK3OO5K8T (bisindolylmaleimide) RN - NI40JAQ945 (Tetradecanoylphorbol Acetate) SB - IM MH - Animals MH - Antibodies MH - Brain-Derived Neurotrophic Factor/analysis/immunology/metabolism MH - Carbazoles/pharmacology MH - Carcinogens/pharmacology MH - Cells, Cultured MH - Cerebral Cortex/cytology MH - Culture Media, Conditioned/pharmacology MH - Diglycerides/pharmacology MH - Enzyme Inhibitors/pharmacology MH - Indoles/pharmacology MH - Isoenzymes/antagonists & inhibitors/metabolism MH - Lipopolysaccharides/pharmacology MH - Maleimides/pharmacology MH - Microglia/*cytology/drug effects/*metabolism MH - Nerve Growth Factor/analysis/immunology/metabolism MH - Nerve Growth Factors/analysis/immunology/*metabolism MH - Neurotrophin 3/analysis/immunology/metabolism MH - Protein Kinase C/antagonists & inhibitors/metabolism MH - Protein Kinase C-alpha MH - Rats MH - Tetradecanoylphorbol Acetate/pharmacology EDAT- 2001/08/09 10:00 MHDA- 2001/09/14 10:01 CRDT- 2001/08/09 10:00 PHST- 2001/08/09 10:00 [pubmed] PHST- 2001/09/14 10:01 [medline] PHST- 2001/08/09 10:00 [entrez] AID - 10.1002/jnr.1157 [doi] PST - ppublish SO - J Neurosci Res. 2001 Aug 15;65(4):322-31. doi: 10.1002/jnr.1157.