Phenylethanoid glycosides as a new macrophage-activating factor

苯乙醇苷作为新的巨噬细胞激活因子

• 批准号: 09672243
• 负责人: INOUE Makoto
• 金额: $ 2.05万
• 依托单位: Nagoya City University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09672243/
• 关键词: Acteoside; Phenylethanoid glycoside; Hydrogen peroxide; Macrophage; Endothelial cell; TNF-α; IL-1β; IL-6; ICAM-1; シグナル伝達

Acteoside, a phenylpropanoid glycoside, was found to induce cytokine production and adhesion molecule expression on macrophages or SV4O-transformed endothelial cells (GEN-T). On the other hand, acteoside showed cytotoxicity against various kinds of tumor cells. In this study we studied whether the pathway of signal transduction in cell activation and cell death was different or not. Acteoside produced hydrogen peroxide which was detected by scopletin method as early as 1 min after its addition into medium. Its hydrogen peroxide production was dependent on the amount of acteoside and was abolished by the pretreatment with catalase. When the relationship between the amount of produced hydrogen peroxide and the intensity of cytotoxicity against tumor cells was examined, cell death was induced with the amount of produced hydrogen peroxide. In addition catalase completely inhibited acteoside-induced cell death. In contrast, cell adhesion molecule expression on GEN-T cells by acteoside was not influenced by pretreatment with catalase, suggesting that hydrogen peroxide was not implicated in the signal transduction of GEN-T cell activation by acteoside. We so far considered reactive oxygen species, intracellular calcium and protein phosphorylation as second messenger of signal transduction elicited by acteoside, whereas acteoside-derived hydrogen peroxide, and phosphorylation mediated by hydrogen peroxide would be negated by the facts described above. The precise mechanism of signal transduction remains to be clarified in the future.

Acteoside 是一种苯丙酸苷，被发现可诱导巨噬细胞或 SV4O 转化的内皮细胞 (GEN-T) 上细胞因子的产生和粘附分子的表达。另一方面，acteoside对多种肿瘤细胞表现出细胞毒性。在本研究中，我们研究了细胞激活和细胞死亡的信号转导途径是否不同。 Acteoside 产生过氧化氢，在加入培养基后 1 分钟即可通过 scopletin 方法检测到过氧化氢。其过氧化氢的产生取决于类叶升麻苷的量，并通过过氧化氢酶预处理而消除。当检查产生的过氧化氢的量和对肿瘤细胞的细胞毒性强度之间的关系时，产生的过氧化氢的量诱导细胞死亡。此外，过氧化氢酶完全抑制类叶升麻苷诱导的细胞死亡。相比之下，acteoside在GEN-T细胞上的细胞粘附分子表达不受过氧化氢酶预处理的影响，这表明过氧化氢不参与acteoside激活GEN-T细胞的信号转导。到目前为止，我们认为活性氧、细胞内钙和蛋白质磷酸化是由升糖苷引发的信号转导的第二信使，而升糖苷衍生的过氧化氢和由过氧化氢介导的磷酸化将被上述事实否定。信号转导的精确机制有待未来进一步阐明。

项目成果

Makoto Inoue: "Induction of Cytokines by Phenylpropanoid Glycoside Acteoside" Biol.Pharm.Bull.21・12. 1394-1395 (1998)

井上诚：“苯丙酸苷Aceoside诱导细胞因子”Biol.Pharm.Bull.21・12 1394-1395（1998）

Iclal Saracoglu: "Selective cytotoxic and cytostatic activity of some phenylpropanoid glycosid" Fitoterapia. 68 (5). 434-438 (1997)

Iclal Saracoglu：“某些苯丙素糖苷的选择性细胞毒性和细胞抑制活性”Fitorapia。

Makoto Inoue: "Induction of apoptotic cell death in HL-60 cells by acteoside,a phenylproparoid・・・・" Biol.Pharm.Bull.21 (1). 81-83 (1998)

Makoto Inoue：“苯丙甲苷诱导 HL-60 细胞凋亡细胞死亡……”Biol.Pharm.Bull.21 (1) (1998)。

Makoto Inoue: "Induction of Cytokines by Phenyl-propanoid Glycoside Acteoside" Biol.Pharm.Bull. 21 (12). 1394-1395 (1998)

Makoto Inoue：“苯丙酸苷 Acteoside 诱导细胞因子”Biol.Pharm.Bull。