Abstract
The protein kinase C (PKC) is known to be a critical component in the signaling cascades that lead to astrocyte-activation. To further understand the mechanism of PKC signaling in astrocyte-activation, we investigated the effect of SSeCKS, a PKC substrate, on LPS-induced cytokine expression in astrocytes by RT-PCR and enzyme-linked immunosorbent assay. Exposure of the cells to LPS induced rapid translocation of SSeCKS to the perinuclear sides, ERK activation and pronounced TNF-alpha production, which can be inhibited by the PKC inhibitor Gö6983. By using siRNA knockdown of SSeCKS expression, LPS-induced signaling events were partly inhibited, including ERK activation, inducible TNF-alpha biosynthesis and secretion. These results suggest that SSeCKS is involved in the LPS-induced TNF-alpha expression in astrocytes mediated by PKC.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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A Kinase Anchor Proteins
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Animals
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Animals, Newborn
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Astrocytes / immunology*
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Astrocytes / metabolism*
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Cell Cycle Proteins / genetics
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Cell Cycle Proteins / metabolism*
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Lipopolysaccharides / pharmacology*
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MAP Kinase Signaling System / immunology
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Mitogen-Activated Protein Kinase 1 / metabolism
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Mitogen-Activated Protein Kinase 3 / metabolism
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Neuroimmunomodulation / physiology
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Protein Kinase C / metabolism
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RNA, Small Interfering
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Rats
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Rats, Sprague-Dawley
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Transfection
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Tumor Necrosis Factor-alpha / biosynthesis*
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Tumor Necrosis Factor-alpha / metabolism
Substances
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A Kinase Anchor Proteins
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Akap12 protein, rat
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Cell Cycle Proteins
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Lipopolysaccharides
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RNA, Small Interfering
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Tumor Necrosis Factor-alpha
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Protein Kinase C
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Mitogen-Activated Protein Kinase 1
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Mitogen-Activated Protein Kinase 3