Fundamental studies for development of a novel anti-tumor drug based on perchloric acid-soluble protein

基于高氯酸可溶性蛋白的新型抗肿瘤药物开发基础研究

• 批准号: 23658244
• 负责人: KANOUCHI HIROAKI
• 金额: $ 2万
• 依托单位: Kagoshima University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Challenging Exploratory Research
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2013
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-23658244/
• 关键词: ガン細胞; 細胞増殖; タンパク質高次構造変化; 抗がん剤; ケミカルライブラリー; レポーターアッセイ; タンパク質高次構造

Perchloric acid-soluble protein (PSP) has an anti-proliferating activity. Its activity seems to be suppressed in cells, because the PSP exists in proliferating cells. Crystal structural analysis of PSP shows that PSP exist as a homo-trimer. Our preliminary experiment, however, suggested PSP existed not only timer but also monomer or dimer. To elucidate that changing higher-order protein structure of PSP is related to cell proliferation, we evaluated the state of higher-order protein structure of PSP during liver regeneration after partial hepatectomy in rats. As a result, PSP existed as trimer in normal liver, but the ratio of trimer of PSP decreased after hepatectomy and the ration of monomer or dimer of PSP increased until liver weight returned to the intact weight. It is suspected monomer or dimer PSP not to suppress cell proliferation. Additionally, we identified the DNA position for expression and regulation of PSP mRNA. We identified two molecules to induce PSP expression.

高氯酸可溶性蛋白（PSP）具有抗增殖活性。它的活性似乎在细胞中受到抑制，因为PSP存在于增殖细胞中。PSP的晶体结构分析表明，PSP以同源三聚体形式存在。初步实验表明PSP不仅存在计时体，而且还存在单体或二聚体。为了阐明PSP高阶蛋白结构的改变与细胞增殖有关，我们评估了大鼠部分肝切除后肝再生过程中PSP高阶蛋白结构的状态。结果表明，PSP在正常肝组织中以三聚体形式存在，肝切除后PSP三聚体比例下降，单体或二聚体比例上升，直至肝重恢复正常。单体或二聚体PSP可能不抑制细胞增殖。此外，我们确定了PSP mRNA表达和调控的DNA位置。我们鉴定了两种诱导PSP表达的分子。

项目成果

High Dose of Pyridoxine Induces IGFBP-3 mRNA Expression in MCF-7 Cells and Its Induction Is Inhibited by the p53-Specific Inhibitor Pifithrin-.ALPHA.

高剂量吡哆醇诱导 MCF-7 细胞中 IGFBP-3 mRNA 表达，并且其诱导受到 p53 特异性抑制剂 Pifithrin-.ALPHA 的抑制。

• DOI: 10.3177/jnsv.57.280
• 发表时间: 2011
• 期刊: Journal of Nutritional Science and Vitaminology
• 影响因子: 1.6
• 作者: Nakari Miwa;Kanouchi Hiroaki;Oka Tatsuzo.
• 通讯作者: Oka Tatsuzo.

Plasma homocysteine concentrations in novel microminipigs.

• 发表时间: 2014-07
• 期刊: In vivo
• 影响因子: 2.3
• 作者: Toshiaki Kakimoto;Akira Otsuka;H. Kawaguchi;K. Ogata;A. Tanimoto;H. Kanouchi

Low pyridoxine concentrations enhance lipopolysaccharide-stimulated gene expression of cyclooxygenase-2 and inducible nitric oxide synthase in RAW264.7 cells

低浓度吡哆醇增强脂多糖刺激的 RAW264.7 细胞中环氧合酶-2 和诱导型一氧化氮合酶的基因表达

• 发表时间: 2013
• 期刊: J. Nutr. Sci. Vitaminol
• 作者: Toshiaki Kakimoto;Akira Otsuka;Hiroaki Kawaguchi;Kenji Ogata;Akihide Tanimoto;Hiroaki Kanouchi;Kanouchi H
• 通讯作者: Kanouchi H

High Dose of Pyridoxine Induces IGFBP-1 mRNA Expression in MCF-7 Cells and Its Induction is Inhibited by the p53-specific Inhibitor Pifithrin-α

高剂量吡哆醇诱导 MCF-7 细胞中 IGFBP-1 mRNA 表达，且其诱导受到 p53 特异性抑制剂 Pifithrin-α 的抑制

• 发表时间: 2011
• 期刊: J. Nutr. Sci.Vitaminol
• 作者: Nakari M;Kanouchi H;Oka T
• 通讯作者: Oka T