权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Elucidation for anti-apoptotic action of tetrahydrobiopterin in osteoblastic cells

阐明四氢生物蝶呤在成骨细胞中的抗凋亡作用

基本信息

批准号：
10671758
负责人：
MOGI Makio
金额：
$ 2.56万
依托单位：
Department of Pharmacology, School of Dentistry, Aichi-Gakuin University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 1999
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10671758/
关键词：
osteoblasts apoptosis tetrahydrobiopterin cytokine

项目摘要

We investigated the effects of 5, 6, 7, 8-tetrahydrobiopterin (BH4), a cofactor for nitric oxide (NO) synthase, on NO toxicity in mouse osteoblastic cell line MC3T3-E1 cells. 1) Proinflammatory cytokine mixture (TNF-α, IL-1β, and IFN-γ) and SNAP, an NO generator, decreased cell viability, but sepiapterin, which was converted intracellularly to BH4, increased it. Flow cytometric analysis showed that the reduction of cell viability by cytokines may be based upon cell death by apoptosis, but not lytic death as in necrosis. 2) Cytokine treatment caused the production of BH4. 3) In the presence of BH4, cytokines resulted in a statistically pronounced reduction (*p<0.05) in the amount of DNA fragmentation. These results suggest that the apoptotic cell death in response to cytokines is ascribed to NO and is protective by BH4. BH4 may act as the counterpart and counterbalance to NO-toxicity in MC3T3-E1 cells. 4) Actinobacillus actinomycetemcomitans (AA) has been implicated in the etiology of localized juvenile periodontitis (LJP) and the capsular-like polysaccharide antigen (CPA) from AA, is a potent mediator of bone resorption. CPA contains a potent antiproliferative polysaccharide whose activity is associated with apoptotic cell death in mouse MC3T3-E1 and human osteosarcoma, suggesting that apoptotic cell death in osteoblastic cells is associated with the pathogenesis of LJP. The elucidation of apoptotic mechanism may provide the therapeutic potential information for LJP.

我们研究了一氧化氮（NO）合酶辅因子5，6，7，8-四氢生物蝶呤（BH 4）对小鼠成骨细胞系MC 3 T3-E1细胞NO毒性的影响。1)促炎细胞因子混合物（TNF-α、IL-1β和IFN-γ）和SNAP（一种NO产生剂）降低细胞活力，但在细胞内转化为BH 4的sepiapterin增加细胞活力。流式细胞术分析表明，细胞因子降低细胞活力可能是基于细胞凋亡引起的细胞死亡，而不是坏死中的溶解性死亡。2)细胞因子处理引起BH 4的产生。3)在BH 4存在下，细胞因子导致DNA片段化量的统计学显著降低（*p<0.05）。这些结果表明，响应于细胞因子的凋亡性细胞死亡归因于NO，并且由BH 4保护。BH 4可能是NO对MC 3 T3-E1细胞毒性的对应物和平衡物。4)伴放线放线杆菌（Actinobacillusactinomycetemcomitans，AA）与局限性青少年牙周炎（localizedjuveniorperiodontitis，LJP）的发病有密切关系，其产生的荚膜样多糖抗原（capsular-like polysaccharide antigen，CPA）是骨吸收的重要介质。CPA含有一种有效的抗增殖多糖，其活性与小鼠MC 3 T3-E1和人骨肉瘤中的凋亡性细胞死亡相关，表明成骨细胞中的凋亡性细胞死亡与LJP的发病机制相关。阐明LJP的凋亡机制可能为LJP的治疗提供潜在的信息。