Medizinische Universität Graz - Research portal
Selected Publication:
Egger, T; Hammer, A; Wintersperger, A; Goti, D; Malle, E; Sattler, W.
Modulation of microglial superoxide production by alpha-tocopherol in vitro: attenuation of p67(phox) translocation by a protein phosphatase-dependent pathway.
J NEUROCHEM 2001 79: 1169-1182.
Doi: 10.1046%2Fj.1471-4159.2001.00641.x
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- Leading authors Med Uni Graz
- Sattler Wolfgang
- Co-authors Med Uni Graz
- Hammer Astrid
- Malle Ernst
- Wintersperger Andrea
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- Abstract:
- As in other phagocytic cells, the NADPH-oxidase system in microglia is thought to be primarily responsible for the production of superoxide anion radicals (O2(-.), a potentially cytotoxic reactive oxygen species. The assembly of a functional NADPH-oxidase complex at the plasma membrane depends on the phosphorylation and subsequent translocation of several cytosolic subunits. Immunocytochemical and subcellular fractionation experiments performed during the present study revealed that the NADPH-oxidase subunit p67(phox) translocates from the cytosol to the plasma membrane upon stimulation. Pre-incubation of microglia in alpha-tocopherol (alphaTocH) containing medium decreased O2(-.) production in a time- and concentration-dependent manner, findings attributed to attenuated p67(phox) translocation to the plasma membrane. Moreover, alphaTocH-supplementation of the culture medium resulted in decreased microglial protein kinase C (PKC) activities, an effect that could be partially or completely reversed by the addition of protein phosphatase inhibitors (okadaic acid and calyculin A). The addition of the PKC-inhibitor staurosporine inhibited the microglial respiratory burst in a manner comparable to alphaTocH. The addition of okadaic acid or calyculin A completely restored O2(-.) production in alphaTocH-supplemented cells. The present findings suggest that alphaTocH inactivates PKC via a PP1 or PP2A-mediated pathway and, as a consequence, blocks the phosphorylation-dependent translocation of p67(phox) to the plasma membrane. As a result, O2(-.) production by the microglial NADPH-oxidase system is substantially inhibited.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals -
- Antioxidants - pharmacology
- Cell Membrane - enzymology
- Cells, Cultured - drug effects
- Cytosol - enzymology
- Dose-Response Relationship, Drug - enzymology
- Enzyme Inhibitors - pharmacology
- Mice - pharmacology
- Microglia - drug effects
- NADH, NADPH Oxidoreductases - metabolism
- NADPH Oxidase - metabolism
- Nerve Tissue Proteins - antagonists and inhibitors
- Okadaic Acid - pharmacology
- Oxazoles - pharmacology
- Phosphoprotein Phosphatase - antagonists and inhibitors
- Phosphoproteins - antagonists and inhibitors
- Phosphorylation - drug effects
- Protein Kinase C - antagonists and inhibitors
- Protein Processing, Post-Translational - drug effects
- Protein Transport - drug effects
- Rats - drug effects
- Respiratory Burst - drug effects
- Staurosporine - pharmacology
- Superoxides - metabolism
- Swine - metabolism
- alpha-Tocopherol - pharmacology
- Find related publications in this database (Keywords)
- BV-2 cells
- microglia
- NADPH-oxidase
- p67(phox)
- respiratory burst
- vitamin E