钙调蛋白抑制剂W-7和三氟拉嗪在无细胞体系中可阻断花生四烯酸对NADPH氧化酶的非钙调蛋白依赖性激活。

Calmodulin inhibitors, W-7 and TFP, block the calmodulin-independent activation of NADPH-oxidase by arachidonate in a cell-free system.

作者信息

Sakata A, Ida E, Tominaga M, Onoue K

机构信息

Department of Biochemistry, Kumamoto University Medical School, Japan.

出版信息

Biochem Biophys Res Commun. 1987 Oct 14;148(1):112-9. doi: 10.1016/0006-291x(87)91083-7.

DOI:10.1016/0006-291x(87)91083-7

PMID:2823798

Abstract

The calmodulin inhibitor, N-(6-aminohexyl)-5-chloro-1-naphthalene sulfonamide (W-7), or trifluoperazine inhibited not only Fc gamma-receptor mediated cytosolic free Ca2+ increase and O2- generation in macrophages, but also an arachidonate-induced activation of NADPH-oxidase in a cell-free system. Although these results suggested the involvement of Ca2+-calmodulin system, the cell-free activation of NADPH-oxidase occurred in the presence of EGTA and addition of calmodulin had no effect. Furthermore W-7 shifted the optimal concentration of arachidonate required for the activation to a higher level, suggesting that W-7 may block the interaction between arachidonate and NADPH-oxidase system rather than inhibiting a Ca2+-calmodulin system.

摘要

钙调蛋白抑制剂N-(6-氨基己基)-5-氯-1-萘磺酰胺（W-7）或三氟拉嗪不仅抑制巨噬细胞中Fcγ受体介导的胞质游离Ca2+增加和O2-生成，还抑制无细胞体系中花生四烯酸诱导的NADPH氧化酶激活。尽管这些结果提示Ca2+-钙调蛋白系统参与其中，但NADPH氧化酶的无细胞激活在EGTA存在的情况下发生，添加钙调蛋白并无作用。此外，W-7将激活所需的花生四烯酸最佳浓度提高到更高水平，表明W-7可能阻断花生四烯酸与NADPH氧化酶系统之间的相互作用，而非抑制Ca2+-钙调蛋白系统。