TPA induces the expression of EC-SOD in human monocytic THP-1 cells: Involvement of PKC, MEK/ERK and NOX-derived ROS

Abstract

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.

Keywords::

• extracellular-superoxide dismutase
• protein kinase C
• mitogen-activated protein kinase
• reactive oxygen species
• monocytic differentiation

Declaration of interest The authors report no conflicts of interest. The authors alone are responsible for the content writing of the paper. This study was supported in part by a Grant-in-Aid for Scientific Research from the Japan Society for the Promotion for Science (TK: No. 23790190; TA: No. 21590169).

This paper was first published online on Early Online on 2 March 2012.