TPA induces the expression of EC-SOD in human monocytic THP-1 cells: involvement of PKC, MEK/ERK and NOX-derived ROS.
Extracellular-superoxide dismutase (EC-SOD) is a major SOD isozyme mainly present in the vascular wall. EC-SOD is also observed in monocytes/macrophages, and its high expression contributes to the suppression of atherosclerosis by scavenging superoxide. The molecular mechanisms governing cell-specific expression of EC-SOD are mostly unknown, while the anti-oxidative effect of EC-SOD is well recognized. In this study, we investigated the expression of EC-SOD during 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced monocytic differentiation of THP-1 cells, which is not expressing its gene in the basal phase. We confirmed the significant induction of EC-SOD in a TPA time-dependent manner, and that induction was completely blocked by pre-treatment with GF109203X, an inhibitor of protein kinase C, U0126 and PD98059, inhibitors of mitogen-activated protein kinase kinase/extracellular-signal regulated kinase. Moreover, we determined the involvement of NADPH oxidase-derived reactive oxygen species in that induction. Overall, we considered that these results may contribute to clarify the cell-specific expression of EC-SOD.
Laboratory of Clinical Pharmaceutics, Gifu Pharmaceutical University, Gifu, Japan.
Junya
J
Makino
Tetsuro
T
Kamiya
Hirokazu
H
Hara
Tetsuo
T
Adachi
D002070:Butadienes / Q000494:pharmacology; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005419:Flavonoids / Q000494:pharmacology; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D020935:MAP Kinase Signaling System; D008264:Macrophages / Q000378:metabolism; D008301:Maleimides / Q000494:pharmacology; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009000:Monocytes / Q000166:cytology / Q000378:metabolism*; D019255:NADPH Oxidases / Q000378:metabolism; D009570:Nitriles / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000096:biosynthesis* / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
D002070:Butadienes; D005419:Flavonoids; D007211:Indoles; D008301:Maleimides; D009570:Nitriles; D017382:Reactive Oxygen Species; C113580:U 0126; D013482:Superoxide Dismutase; D019255:NADPH Oxidases; D011493:Protein Kinase C; D048049:Extracellular Signal-Regulated MAP Kinases; D020928:Mitogen-Activated Protein Kinases; C070515:bisindolylmaleimide I; D013755:Tetradecanoylphorbol Acetate; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one