PMID: 9450681Feb 5, 1998Paper

Induction of nerve growth factor synthesis by sphingomyelinase and ceramide in primary astrocyte cultures

Brain Research. Molecular Brain Research
I Galve-RoperhI Díaz-Laviada

Abstract

Astrocytes synthesize nerve growth factor (NGF) in response to pro-inflammatory cytokines. To further study the signaling mechanism involved in this induction of NGF production, the sphingomyelin (SM) pathway was studied. Addition of exogenous neutral SMase (Staphylococcus aureus) or C2-ceramide to primary cultures of newborn rat cortical astrocytes elicited a dose-response increase of NGF synthesis, with maximal effect at 1 U/ml and 25 microM, respectively. Induction of NGF synthesis by SMase and ceramide was shown to be independent of classical PKC activity. Intracellular cAMP-raising agents, such as forskolin and 3-isobutyl-1-methylxanthine, partially prevented the SMase- and C2-ceramide-induced secretion of NGF to the cell supernatant. PD098059 and apigenin, inhibitors of the mitogen-activated protein (MAP) kinase pathway, produced a dose-response inhibition of the SMase- and C2-cer-induced release of NGF. This observation points to the possibility that regulation of NGF synthesis and secretion by the SMase pathway may be mediated downstream by the MAP kinase cascade. As a matter of fact, pre-treatment of astrocytes with SMase or C8-ceramide led to an increased phosphorylation of raf-1. Moreover, MAP kinase activity was enh...Continue Reading

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Citations

Jul 6, 2000·European Journal of Pharmacology·K TakumaT Matsuda
Oct 19, 1999·Brain Research. Brain Research Reviews·I Semkova, J Krieglstein
Sep 24, 2004·The European Journal of Neuroscience·H ZrouriF Courtin
Jan 22, 2005·Brain Research. Molecular Brain Research·Hidemi YoshidaKei Satoh
Dec 2, 2004·Brain Research. Brain Research Reviews·Laura Colombaioni, Mercedes Garcia-Gil
Dec 20, 2011·Archives of Biochemistry and Biophysics·E AlbiF S Ambesi-Impiombato
Jan 18, 2005·The Journal of International Medical Research·U A MalcokI H Aydin
Apr 3, 2007·Neurochemical Research·Bing XueXiao-Min Wang

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