PMID- 11841576 OWN - NLM STAT- MEDLINE DCOM- 20020304 LR - 20190630 IS - 0022-3042 (Print) IS - 0022-3042 (Linking) VI - 80 IP - 4 DP - 2002 Feb TI - Ceramide activates microglia to enhance the production/secretion of brain-derived neurotrophic factor (BDNF) without induction of deleterious factors in vitro. PG - 697-705 AB - In analyzing the regulation of neurotrophin production/secretion from microglia, C8-ceramide (D-erythro-sphingosine, N-octanoyl-) was found to induce secretion of brain-derived neurotrophic factor (BDNF) from microglia in vitro. In the present study, the action of C8-ceramide in secreting neurotrophic and harmful factors was investigated and compared with the effects of lipopolysaccharide (LPS). C8-ceramide as well as LPS enhanced the production/secretion of BDNF but, different from LPS, did not induce tumor necrosis factor alpha, interleukin-1beta, or nitric oxide. The C8-ceramide-induced BDNF release was significantly suppressed by protein kinase C (PKC) inhibitor, bisindolylmaleimide, which targets PKC isoforms, alpha, beta, gamma, delta and epsilon. However, it was not suppressed by a specific inhibitor of PKCalpha. Furthermore, PKCbeta and gamma were undetected in the microglia. Therefore, PKCdelta and/or epsilon appear to be functioning PKC isoforms. In contrast, none of the mitogen-activated protein kinases (MAPKs) and none of the transcription factors, including the cAMP response element-binding transcription factor (CREB) and nuclear factor kappaB (NFkappaB) were activated in the microglia in response to C8-ceramide. These results indicate that ceramide-induced BDNF release in microglia is mediated by a signaling pathway associated with PKCdelta and/or epsilon, but not with activation of MAPKs, CREB and NFkappaB. FAU - Nakajima, Kazuyuki AU - Nakajima K AD - Institute of Life Science, Soka University, Hachioji, Tokyo, Japan. nakajima@t.soka.ac.jp FAU - Tohyama, Yoko AU - Tohyama Y FAU - Kohsaka, Shinichi AU - Kohsaka S FAU - Kurihara, Tadashi AU - Kurihara T LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - J Neurochem JT - Journal of neurochemistry JID - 2985190R RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Ceramides) RN - 0 (Enzyme Inhibitors) RN - 0 (Interleukin-1) RN - 0 (Lipopolysaccharides) RN - 0 (Nerve Growth Factors) RN - 0 (RNA, Messenger) RN - 0 (Transcription Factors) RN - 0 (Tumor Necrosis Factor-alpha) RN - 9001-91-6 (Plasminogen) RN - 9061-61-4 (Nerve Growth Factor) RN - EC 2.7.11.13 (Protein Kinase C) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinases) SB - IM MH - Animals MH - Brain-Derived Neurotrophic Factor/*biosynthesis/genetics/*metabolism MH - Cells, Cultured MH - Ceramides/*pharmacology MH - Enzyme Activation/drug effects MH - Enzyme Inhibitors/pharmacology MH - Interleukin-1/analysis/biosynthesis/metabolism MH - Lipopolysaccharides/pharmacology MH - Microglia/cytology/*drug effects/*metabolism MH - Mitogen-Activated Protein Kinases/metabolism MH - Nerve Growth Factor/analysis/biosynthesis/metabolism MH - Nerve Growth Factors/analysis/biosynthesis/metabolism MH - Plasminogen/metabolism MH - Protein Kinase C/antagonists & inhibitors/metabolism MH - RNA, Messenger/analysis/metabolism MH - Rats MH - Reverse Transcriptase Polymerase Chain Reaction MH - Transcription Factors/metabolism MH - Tumor Necrosis Factor-alpha/analysis/biosynthesis/metabolism EDAT- 2002/02/14 10:00 MHDA- 2002/03/05 10:01 CRDT- 2002/02/14 10:00 PHST- 2002/02/14 10:00 [pubmed] PHST- 2002/03/05 10:01 [medline] PHST- 2002/02/14 10:00 [entrez] AID - 752 [pii] AID - 10.1046/j.0022-3042.2001.00752.x [doi] PST - ppublish SO - J Neurochem. 2002 Feb;80(4):697-705. doi: 10.1046/j.0022-3042.2001.00752.x.