Vitamin E (alpha-tocopherol) attenuates cyclo-oxygenase 2 transcription and synthesis in immortalized murine BV-2 microglia
| Autor: | Ernst Malle, Andrea Wintersperger, Rainer Amann, Rufina Schuligoi, Wolfgang Sattler, Tamara Egger |
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| Jazyk: | angličtina |
| Rok vydání: | 2003 |
| Předmět: |
MAPK/ERK pathway
Lipopolysaccharides Biology Mitogen-activated protein kinase kinase Biochemistry Dinoprostone chemistry.chemical_compound Mice Phosphoprotein Phosphatases Animals Vitamin E ASK1 Protein Phosphatase 2 Protein kinase A Molecular Biology Protein kinase C Cell Line Transformed MAP kinase kinase kinase Cyclin-dependent kinase 2 NF-kappa B Cell Biology Cell biology Enzyme Activation Isoenzymes Chelerythrine chemistry Cyclooxygenase 2 Prostaglandin-Endoperoxide Synthases biology.protein Microglia Mitogen-Activated Protein Kinases Research Article |
| Popis: | One of the immediate early microglial genes that are up-regulated in response to proinflammatory stimuli is cyclo-oxygenase 2 (COX-2). In the present study, we have investigated the effects of alpha-tocopherol (alpha TocH), an essential constituent of the nervous system, on the activation of COX-2 in lipopolysaccharide (LPS)-stimulated mouse BV-2 microglia. In unstimulated BV-2 cells, COX-2 mRNA and protein were almost undetectable but were strongly up-regulated in response to LPS. Activation of COX-2 protein synthesis in LPS-stimulated BV-2 cells involved activation of the extracellular-signal-regulated kinase 1/2 (ERK1/2) and p38 mitogen-activated protein kinase (MAPK) pathway and was sensitive to the protein kinase C (PKC) inhibitors staurosporine and chelerythrine, and the MAP kinase/ERK kinase 1/2 inhibitors PD98059 and U0126. Supplementation of BV-2 cells with alpha TocH before LPS stimulation resulted in pronounced up-regulation of protein phosphatase 2A (PP2A) activity, down-regulation of PKC activity, ERK1/2 phosphorylation and nuclear factor kappa B (NF kappa B) activation. As a result, COX-2 protein levels and prostaglandin E(2) production were significantly lower in alpha TocH-supplemented cells. The effects of alpha TocH on PKC activity could be reverted by calyculin A and okadaic acid, two PP inhibitors. In summary, our results suggest that alpha TocH activates microglial PP2A activity and thereby silences an LPS-activated PKC/ERK/NF kappa B signalling cascade resulting in significantly attenuated COX-2 protein synthesis. These in vitro results imply that alpha TocH could induce quiescence to pathways that are associated with acute or chronic inflammatory conditions in the central nervous system. |
| Databáze: | OpenAIRE |
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