Yamashita M, Niki H, Yamada M, Mue S, Ohuchi K
Department of Pathophysiological Biochemistry, Faculty of Pharmaceutical Sciences, Tohoku University, Aoba Aramaki, Sendai, Miyagi, Japan.
Eur J Pharmacol. 1997 Nov 5;338(2):151-8. doi: 10.1016/s0014-2999(97)81943-7.
In RAW 264.7 cells, a murine macrophage cell line, treatment with lipopolysaccharide (1 to 10 ng/ml) stimulated production of nitric oxide (NO), which was inhibited by L-N(G)-monomethyl-L-arginine acetate, an inhibitor of NO synthase. Auranofin, an orally active chrysotherapeutic agent, also inhibited the lipopolysaccharide-induced NO production in a concentration-dependent manner (0.3 to 3 microM). Other gold salts such as aurothioglucose and aurothiomalate had no effect. Western blot analysis demonstrated that the lipopolysaccharide (10 ng/ml)-induced expression of inducible NO synthase protein was inhibited by auranofin as well as by the protein synthesis inhibitor cycloheximide. In addition, the lipopolysaccharide-induced increase in the level of mRNA for inducible NO synthase was also lowered by auranofin. Furthermore, auranofin showed no direct effect on the conversion of [3H]arginine to [3H]citrulline by the cell lysate. These findings indicate that auranofin inhibits lipopolysaccharide-induced NO production by suppressing the expression of inducible NO synthase.
在RAW 264.7细胞（一种小鼠巨噬细胞系）中，用脂多糖（1至10纳克/毫升）处理可刺激一氧化氮（NO）的产生，而这种产生会被一氧化氮合酶抑制剂L-N(G)-单甲基-L-精氨酸醋酸盐所抑制。金诺芬是一种口服有效的金制剂，它也以浓度依赖的方式（0.3至3微摩尔）抑制脂多糖诱导的NO产生。其他金盐如硫代葡萄糖金和硫代苹果酸金则没有效果。蛋白质印迹分析表明，金诺芬以及蛋白质合成抑制剂环己酰亚胺均可抑制脂多糖（10纳克/毫升）诱导的诱导型一氧化氮合酶蛋白的表达。此外，金诺芬还降低了脂多糖诱导的诱导型一氧化氮合酶mRNA水平的升高。此外，金诺芬对细胞裂解液将[3H]精氨酸转化为[3H]瓜氨酸的过程没有直接影响。这些发现表明，金诺芬通过抑制诱导型一氧化氮合酶的表达来抑制脂多糖诱导的NO产生。
