Physiological role of vitamin K2 (manaquinone-4) that is converted from other vitamin K analogue in animal organs

由其他维生素 K 类似物转化而来的维生素 K2（manaquinone-4）在动物器官中的生理作用

基本信息

批准号：
18580111
负责人：
SHIRAKAWA Hitoshi
金额：
$ 2.49万
依托单位：
Tohoku University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2006
资助国家：
日本
起止时间：
2006 至 2007
项目状态：
已结题

项目摘要

We analyzed the physiological role of de novo synthesized menaquinone-4 (MK-4) in mammal, and also molecular mechanism of anti-inflammation and regulation of steroidogenesis by vitamin K. I. We developed the model that has low vitamin K in extra-hepatic tissues without any bleeding sym ptom by feeding of dihydrophylloquinone (dK1) as a vitamin K source, and analyzed its phenotype. The plasma osteocalcin level that is one of bone metabolic markers was significantly increased in dK1 feeding group. On the other hand, plasma calcium level was not changed. Therefore dK1 feeding coup d enhance the differentiation of osteoblast not turn over of bone. II. To clarify the direct involvement of testis MK-4 in steroidogenesis, we administered lipopolysaccharide to the subchronic vitamin K deficient rats without any bleeding and analyzed testosterone production in testis. As a result, the synthesis of testosterone and gene expression of Cyp11a was decreased by LPS treatment depending on testis MK-4 concentration. These results indicate that testis MK-4 shows anti-inflammation effect to keep the normal steroidogenesis. III. We analyzed the molecular mechanism of the anti-inflammation by vitamin K using mouse macrophage derived cells. MK-4 significantly reduced IL-1β, IL-6, and TNFα mRNA stimulated by LPS treatment dose-dependent manner. Conditioned medium treated with MK-4 also has a reducing activity of inflammatory cytokine expression. These results suggested that MK-4 metabolite or something secreted from MK-4 treated cells show anti-inflammatory effect.

我们分析了从头合成的梅纳金酮-4（MK-4）在哺乳动物中的身体作用，还分析了抗炎和调节的分子机制，并通过维生素K对类固醇生成的调节。并分析了其表型。 DK1进食组中骨代谢标记之一的血浆骨钙素水平显着增加。另一方面，血浆钙水平没有改变。因此，DK1进食政变D增强了成骨细胞的分化，而不是翻倒骨头。 ii。为了澄清睾丸MK-4在类固醇发生中的直接参与，我们将脂多糖施用到亚基雄性维生素K缺乏大鼠的情况下，而没有任何出血和分析的睾丸激素产生。结果，睾丸激素的合成和CYP11A的基因表达通过LPS处理降低，具体取决于睾丸MK-4浓度。这些结果表明，睾丸MK-4显示出抗炎作用以保持正常的类固醇生成。 iii。我们使用小鼠巨噬细胞衍生的细胞分析了维生素K抗炎的分子机制。 MK-4显着降低了通过LPS处理剂量依赖性方式刺激的IL-1β，IL-6和TNFαmRNA。用MK-4处理的条件培养基也具有炎症细胞因子表达的降低活性。这些结果表明，MK-4代谢产物或MK-4处理细胞分泌的东西显示出抗炎作用。