The mechanism of the inhibitory action of lipopolysaccharide on anti-cancer drug-induced cell injury

脂多糖抑制抗癌药物引起的细胞损伤的机制

• 批准号: 17590404
• 负责人: YOKOCHI Takashi
• 金额: $ 2.3万
• 依托单位: AICHI MEDICAL UNIVERSITY
• 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 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17590404/
• 关键词: lipopolysaccharide; endotoxin; doxorubicin; p53; macrophage; apoptosis; anti-cancer drug; DNA damage

The effect of lipopolysaccharide (LPS) on doxorubicin (DXB)-induced cell death was studied by using mouse RAW 264.7 macrophage cells. Pretreatment with LPS at 10ng/ml prevented DXB-induced cell death and the inhibition was roughly dependent on the concentration of LPS. The 1 h post-treatment of LPS also prevented DXB-induced cell death. LPS inhibited DNA fragmentation and caspase 3 activation in DXB-treated RAW 264.7 cells, suggesting the prevention of DXB-induced apoptosis. LPS did not significantly inhibit DXB-induced DNA damages detected by a single cell gel electrophoresis (comet) assay. LPS definitely inhibited the stabilization and nuclear translocation of p53 in DXB-treated RAW 264.7 cells. LPS as well as an inhibitor of p53 abolished DXB-induced apoptosis. Therefore, p53 was suggested to play a pivotal role in the prevention of DXB-induced apoptosis in RAW 264.7 cells by LPS.

用小鼠RAW 264.7巨噬细胞研究了脂多糖（LPS）对阿霉素（DXB）诱导的细胞死亡的影响。10 ng/ml的LPS预处理可抑制DXB诱导的细胞死亡，且这种抑制作用与LPS浓度呈明显的依赖关系。LPS处理后1小时也阻止了DXB诱导的细胞死亡。LPS抑制DXB处理的RAW 264.7细胞中的DNA断裂和半胱天冬酶3激活，表明阻止DXB诱导的凋亡。LPS没有显着抑制DXB诱导的DNA损伤检测单细胞凝胶电泳（彗星）试验。LPS明显抑制DXB处理的RAW 264.7细胞中p53的稳定和核转位。LPS以及p53抑制剂消除DXB诱导的细胞凋亡。因此，p53可能在LPS抑制DXB诱导的RAW 264.7细胞凋亡中起重要作用。

项目成果

Defective responsiveness of CD5+ B1 cells to lopopolysaccharide in cytokine production

CD5 B1 细胞在细胞因子产生中对脂多糖的反应缺陷

• 发表时间: 2006
• 期刊: J End Res 12
• 作者: Kida.Y;Shimizu.T;Kuwano.K;Masataka Oda;Koide N et al.
• 通讯作者: Koide N et al.

Lipopolysaccharide prevents apoptosis induced by brefeldin A, an endoplasmic reticulum stress agent, in RAW 264.7 cells

• DOI: 10.1016/j.bbrc.2005.12.050
• 发表时间: 2006-02-10
• 期刊: BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
• 影响因子: 3.1
• 作者: Islam, S;Hassan, F;Yokochi, T
• 通讯作者: Yokochi, T

Lethal endotoxic shock using alpha-galactosylceramide sensitization as a new experimental model of septic shock.

• 发表时间: 2006
• 期刊: Laboratory investigation; a journal of technical methods and pathology
• 作者: Hiroyasu Ito;N. Koide;F. Hassan;S. Islam;G. Tumurkhuu;I. Mori;T. Yoshida;S. Kakumu;H. Moriwaki-H.-Mor

Characterization of biological activities of Brucella melitensis lipopolysaccharide

羊布鲁氏菌脂多糖的生物活性表征

• 发表时间: 2006
• 期刊: Microbiol Immunol 50
• 作者: Nishio M;Okada N;Miki T;Haneda T;Danbara H;Masahiro Nagahama;Tumurkhuu G et al.
• 通讯作者: Tumurkhuu G et al.

A role of mitogen and stress-activated protein kinase 1/2 in survival of lipopolysaccharide-stimulated RAW 264.7 macrophages

有丝分裂原和应激激活蛋白激酶 1/2 在脂多糖刺激的 RAW 264.7 巨噬细胞存活中的作用

• 发表时间: 2005
• 期刊: FEMS Immunol Med Microbiol 43
• 作者: Takayanagi R.;et al.;Mu MM et al.
• 通讯作者: Mu MM et al.