TPA induces the expression of EC-SOD in human monocytic THP-1 cells: Involvement of PKC, MEK/ERK and NOX-derived ROS
TPA induces the expression of EC-SOD in human monocytic THP-1 cells: Involvement of PKC, MEK/ERK and NOX-derived ROS
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DOI：
10.3109/10715762.2012.664841
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发表时间：
2012-05-01
影响因子：
3.3
通讯作者：
Adachi, Tetsuo
中科院分区：
文献类型：
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作者：
Makino, Junya;Kamiya, Tetsuro;Adachi, Tetsuo
细胞外超氧化物歧化酶（EC-SOD）是一种主要存在于血管壁的SOD同工酶。在单核/巨噬细胞中也观察到EC-SOD，其高表达有助于通过清除超氧化物来抑制动脉粥样硬化。EC-SOD的细胞特异性表达的分子机制大多是未知的，而EC-SOD的抗氧化作用是公认的。在这项研究中，我们研究了EC-SOD的表达在12-O-十四烷酰佛波醇-13-乙酸酯（TPA）诱导的单核细胞分化的THP-1细胞，这是不表达其基因的基础阶段。我们证实了显着的诱导EC-SOD在TPA时间依赖性的方式，并诱导完全阻断预处理GF 109203 X，蛋白激酶C，U 0126和PD 98059，抑制剂丝裂原活化蛋白激酶激酶/细胞外信号调节激酶的抑制剂。此外，我们确定了参与NADPH氧化酶衍生的活性氧物种的诱导。总之，我们认为这些结果可能有助于阐明EC-SOD的细胞特异性表达。
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.