Abstract
We have recently reported that attenuated phosphorylation of heat shock protein (HSP) 27 correlates with tumor progression in patients with hepatocellular carcinoma (HCC). In the present study, we investigated what kind of kinase regulates phosphorylation of HSP27 in human HCC-derived HuH7 cells. 12-O-tetradecanoylphorbol-13-acetate (TPA) and 1-oleoyl-2-acetylglycerol, direct activators of protein kinase C (PKC), markedly strengthened the phosphorylation of HSP27. Bisindorylmaleimide I, an inhibitor of PKC, suppressed the TPA-induced levels of HSP27 phosphorylation in addition to its basal levels. Knock down of PKCdelta suppressed HSP27 phosphorylation, as well as p38 mitogen-activated protein kinase (MAPK) phosphorylation. SB203580, an inhibitor of p38 MAPK, suppressed the TPA-induced HSP27 phosphorylation. Our results strongly suggest that activation of PKCdelta regulates the phosphorylation of HSP27 via p38 MAPK in human HCC.
MeSH terms
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Blotting, Western
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Carcinoma, Hepatocellular / metabolism*
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Cell Line, Tumor
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Diglycerides / pharmacology
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Enzyme Activation / drug effects
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Enzyme Activation / physiology
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Enzyme Inhibitors / pharmacology
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Heat-Shock Proteins / metabolism*
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Humans
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Imidazoles / pharmacology
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Liver Neoplasms / metabolism*
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Mitogen-Activated Protein Kinase 1 / metabolism
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Phosphorylation
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Protein Kinase C-delta / antagonists & inhibitors
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Protein Kinase C-delta / genetics
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Protein Kinase C-delta / metabolism*
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Pyridines / pharmacology
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RNA, Small Interfering / pharmacology
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Tetradecanoylphorbol Acetate / pharmacology
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p38 Mitogen-Activated Protein Kinases / antagonists & inhibitors
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p38 Mitogen-Activated Protein Kinases / metabolism
Substances
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Diglycerides
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Enzyme Inhibitors
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Heat-Shock Proteins
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Imidazoles
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Pyridines
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RNA, Small Interfering
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1-oleoyl-2-acetylglycerol
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Protein Kinase C-delta
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Mitogen-Activated Protein Kinase 1
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p38 Mitogen-Activated Protein Kinases
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Tetradecanoylphorbol Acetate
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SB 203580