Evaluation of biological activity of the glycolipids by device cultured cells

通过装置培养细胞评价糖脂的生物活性

• 批准号: 17550163
• 负责人: FUKUOKA Satoshi
• 金额: $ 2.29万
• 依托单位: National Institute of Advanced Industrial Science and Technology
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2007
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-17550163/
• 关键词: Cell; Biological activity; cytokine; Lipopolysaccharide; Lipid A; 抗菌ペプチド; 生理活性; 糖鎖; 脂質

The device cultured cells were applied for biological activity evaluation of glycoconjugates, polysaccharides, and other materials. Lipid A from bacterial lipopolysaccharide(LPS) was used as a model compound that is a biological active center of LPS which located on the outer membrane of Gram-negative bacteria. As a biological activity, cytokine(tumor necrosis factor, TNF-α) production by cultured cells was studied. Homogeneous lipid A samples were isolated and purified from LPS of Erwinia carotovora. In addition, preparation of highly sensitive probe for cell evaluation and study for signal transduction by lipid A was performed. The molecular level interaction of lipid A with antimicrobial peptides was investigated to elucidate the expression mechanisms and deactivation methods. The lipid A induced cytokine production in mononuclear cells showed that the ability of the two peptides to inhibit a TNF-α production correlates with characteristic changes of the biophysical parameters as phase transition, molecular arrangement, etc. These are much stronger expressed for the modified peptide, which apparently is connected with the higher number of positive as well as more hydrophobic amino acids, leading to a stronger amphiphilicity necessary to neutralize the amphiphilic lipid A aggregates. By this study, molecular level mechanism of biological activity for lipid A was introduced. This will lead to the remedy of sepsis and other syndromes introduced by bacterial infection.

该装置培养的细胞用于糖缀合物、多糖和其他材料的生物活性评价。以革兰氏阴性菌外膜脂多糖（LPS）的生物活性中心Lipid A为模型化合物，研究了LPS对革兰氏阴性菌的作用。作为生物活性，研究了培养细胞产生的细胞因子（肿瘤坏死因子，TNF-α）。从胡萝卜软腐欧文氏菌的LPS中分离并纯化了均质脂质A样品。此外，制备了用于细胞评价的高灵敏度探针，并研究了脂质A的信号转导。研究脂质体A与抗菌肽的分子水平相互作用，以阐明表达机制和失活方法。脂质A诱导的单核细胞中细胞因子的产生表明，两种肽抑制TNF-α产生的能力与生物物理参数的特征性变化相关，如相变、分子排列等。这些在修饰肽中表达得更强，这显然与更高的阳性数量以及更多的疏水氨基酸有关，导致中和两亲性脂质A聚集体所需的更强的两亲性。通过本研究，从分子水平上介绍了类脂A的生物活性机制。这将导致败血症和其他由细菌感染引起的综合征的治疗。

项目成果

Characteristic change of membrane behavior of lipid A by the action of magainin 2

Magainin 2 作用下脂质 A 膜行为的特征性变化

• 发表时间: 2007
• 作者: Satoshi Fukuoka;Jorg Howe;Joge Andra;Klaus Brandenburg
• 通讯作者: Klaus Brandenburg

エンドトキシンの活性を抑制するリポペプチドの分子設計

抑制内毒素活性的脂肽的分子设计

• 发表时间: 2006
• 作者: 福岡 聰;ANDRA Jorg;BRANDENBURG Klaus
• 通讯作者: BRANDENBURG Klaus

Physico-chemical and biophysical study of the interaction of hexa-alldheptaacyl lipid A from Erwinia carotovora with magainin 2-derivedantimicrobial peptides

胡萝卜软腐欧文菌六烷基七酰脂 A 与 Magainin 2 衍生抗菌肽相互作用的物理化学和生物物理研究

• 发表时间: 2008
• 期刊: Biochim.Biophys.Acta-Biomembralles 1778
• 作者: Satoshi Fukuoka;Jorg Howe;Jorg Andra;Thomas Gutsmam;Manfred Rossle and Klaus Brandenburg
• 通讯作者: Manfred Rossle and Klaus Brandenburg

細菌外膜脂質のリピドAに抗菌ペプチドが結合したときの膜機能変化

当抗菌肽与脂质 A（一种细菌外膜脂质）结合时，膜功能发生变化

• 发表时间: 2008
• 作者: Ewis AA;et al.;駒口健治;福岡聰・Jorg HOWE・Jorg ANDRA・Klaus BRANDENBURG
• 通讯作者: 福岡聰・Jorg HOWE・Jorg ANDRA・Klaus BRANDENBURG

Investigation into the Interaction of LPS and Lipid A fractions from Erwinia carotovora with antibacterial peptide Magainin 2

胡萝卜软腐欧文氏菌 LPS 和脂质 A 组分与抗菌肽 Magainin 2 相互作用的研究

• 发表时间: 2006
• 作者: S.;Miura;K.;Komaguchi;Y.;Harima;福岡聰・Jorg HOWE・Jorg ANDRA・Klaus BRANDENBURG
• 通讯作者: 福岡聰・Jorg HOWE・Jorg ANDRA・Klaus BRANDENBURG