Identification of intracellular factors involved with apoptosis induction by TGF-β family

TGF-β家族诱导细胞凋亡相关细胞内因子的鉴定

• 批准号: 15390621
• 负责人: FUKUDA Jinichi
• 金额: $ 8.77万
• 依托单位: Kyushu Dental College
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15390621/
• 关键词: Activin; BMP-2; GDF-5; TGF-β family; cell cycle arrest; apoptosis; retinoic acid; malignant transformation; TGF-βファミリ; Smad; 情報伝達

Members of TGF-β superfamily are implicated in regulation of various life phenomenons, including initial development, organ formations and tumor formation. We found that activin A and BMP-2 inhibited cell growth of B cell hybridoma, HS-72 and examined its intracellular transduction mechanism. In the present study, we used three kinds of cells (HS-72 cells, LS-1 cells, and LS-12 cells) and investigated difference of sensitivity for activin A to these cells by flow cytometric analysis.We reported that activin A induced cytotoxic effects to HS-72, and induced G1 arrest in cell cycle and apoptosis at the concentration of 5-50 ng/ml. We clearly that retinoic acid induced a littel cytotoxity to HS-72 and G1 arrest in cell cycle, and that co-stimulation of retinoic acid and activin A potently induced G1 arrest and apoptosis. Activin A or retinoic acid have no effect to LS-1, however, co-stiluration of these factors induced G1 arrest and inclease of sub G1 rate of LS-1 cells. LS-12 showed intermediate type to Activin A and/or retinoic acid.Taken together, the results obtained in this study suggest that cross-talks between activin A and retinoic acid play an important role of the inductin of apoptosis in B lineage cells.

TGF-β超家族成员参与多种生命现象的调节，包括初始发育、器官形成和肿瘤形成。我们发现激活素A和BMP-2抑制了B细胞杂交瘤HS-72的细胞生长，并研究了其细胞内转导机制。本研究以HS-72细胞、LS-1细胞和LS-12细胞为研究对象，通过流式细胞术分析激活素A对不同细胞的敏感性差异，发现激活素A在5-50 ng/ml浓度范围内可诱导HS-72细胞的细胞毒作用，并诱导细胞周期发生G1期阻滞和凋亡。结果表明，维甲酸对HS-72细胞毒性较小，细胞周期阻滞于G1期，而维甲酸与激活素A共刺激则能有效地诱导细胞周期阻滞于G1期，诱导细胞凋亡。激活素A和维甲酸对LS-1细胞无明显作用，但二者联合作用可使LS-1细胞发生G1期阻滞，亚G1期细胞比例增加。LS-12对活化素A和/或视黄酸呈中间型，提示活化素A和视黄酸之间的交联在诱导B系细胞凋亡中起重要作用。

项目成果

Mechanisms involved in apoptosis of human macrophages induces by lipopolysaccharide from Actinobacillus actinomycetemcomitans in the presenceof cycloheximide

放线菌酮存在下放线杆菌脂多糖诱导人巨噬细胞凋亡的机制

• 发表时间: 2004
• 期刊: Infect. Immun 72
• 作者: SUZUki;T.et al.
• 通讯作者: T.et al.

Yoshinouchi et al.: "In vitro and in vivo growth supprcssion of human papillomavirus 16-positive cervical cancer cells by E6 siRNA"Molecular Therapy. 8. 762-768 (2003)

Yoshinouchi 等人：“E6 siRNA 对人乳头瘤病毒 16 阳性宫颈癌细胞的体外和体内生长抑制”分子疗法。

Mechanisms involved in apoptosis of human macrophages induces by lipopolysaccharide from Actinobacillus actinomycetemcomitans in the presence of cycloheximide

放线菌酮存在下放线杆菌脂多糖诱导人巨噬细胞凋亡的机制

• 发表时间: 2004
• 期刊: Infect.Immun 72
• 作者: Suzuki;T. et al.
• 通讯作者: T. et al.

Growth/differentiation factor-S induces growth arrest and apoptosis in mouse B lineage cells with modulation by Smad

生长/分化因子-S 通过 Smad 调节诱导小鼠 B 谱系细胞生长停滞和凋亡

• 发表时间: 2003
• 期刊: Cell Signal 15
• 作者: Nakahara;T.et al.
• 通讯作者: T.et al.

In vitro and in vivo growth suppression of human papillomavirus 16-positive cervical cancer cell by E6 siRNA

E6 siRNA对人乳头瘤病毒16阳性宫颈癌细胞的体外和体内生长抑制

• 发表时间: 2003
• 期刊: Molecular Therapy 8
• 作者: Yoshinouchi;M. et al.
• 通讯作者: M. et al.