2007 Fiscal Year Final Research Report Summary
Physiological role of vitamin K2 (manaquinone-4) that is converted from other vitamin K analogue in animal organs
| Project/Area Number |
18580111
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Food science
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| Research Institution | Tohoku University |
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Principal Investigator |
SHIRAKAWA Hitoshi Tohoku University, TOHOKU UNIVERSITY; GRADUATE SCHOOL OF AGRICULTURAL SCIENCE, ASSOCIATE PROFESSOR (40206280)
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| Co-Investigator(Kenkyū-buntansha) |
KOMAI Michio TOHOKU UNIVERSITY, GRADUATE SCHOOL OF AGRICULTURAL SCIENCE, PROFESSOR (80143022)
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| Project Period (FY) |
2006 – 2007
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| Keywords | vitamin K / menaquinone-4 / anti-inflammation / bone metabolism / macrophage / steroidogenesis / testis |
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| Research Abstract |
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.
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