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新生牛肝中三种低分子化合物牛磺酸、鸟氨酸、肌肽对HL-60细胞凋亡的诱导作用

THE INDUCTION APOPTOSIS OF HL-60 CELLS BY LOW MOLECULAR WEIGHT COMPOUNDS OF TAURINE,ORNITHINE AND CARNOSINE FROM NEW BORN CALF LIVER

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【作者】 张金红卢茜史文静吴祖泽王立生

【Author】 ZHANG Jin-hong~1, LU Qian~1, SHI Wen-jing~1, WU Zu-ze~2, WANG Li-sheng~2(1. Institute of Molecular Biology, Nankai University, Tianjin 300191, China; 2. Institute of Radiation Medicine, Academy of Military Medical Sciences, Beijing 100850, China)

【机构】 南开大学分子生物学研究所军事医学科学院放射医学研究所军事医学科学院放射医学研究所 天津300191天津300191北京100850北京100850

【摘要】 目的:研究三种新生牛肝源低分子化合物:牛磺酸、鸟氨酸、肌肽对HL60白血病细胞增殖的抑制作用并探讨其调控机理。方法:用MTT法分别检测三种活性成分作用后HL60细胞和正常人淋巴细胞的存活率。分别用琼脂糖凝胶电泳,顺磁共振ESR技术,免疫组化法测定其对HL60细胞的核DNA、氧自由基活性和细胞周期蛋白水平的影响。结果:三种化合物能够有效地抑制HL60细胞的增殖,而对正常的人淋巴细胞的生长没有抑制作用;三种化合物使HL60细胞的核DNA产生30kb片段,使HL60细胞内的氧自由基活性降至痕量水平,并下调HL60的p45/skp2的水平,而上调p27/kip的水平。结论:牛磺酸、鸟氨酸、肌肽能够通过调控细胞周期蛋白的水平而选择性的抑制肿瘤细胞的增殖。

【Abstract】 Aim: Clinical studies stated that low molecular weight compounds(<1.0 kd) extracted from the new born calf liver could effectively inhibit the proliferation of tumor cells. In this report, we observed inhibition effects and their regulative mechanisms of taurine, ornithine, carnosine on the proliferation of HL-60 cells. Methods: Three active ingredients i.e. taurine, ornithine and carnosine were separated by ion-exchange chromatographic column and identified from the low molecular weight filtrate of new born calf liver. MTT assay was used to test the survival rate of HL-60 cells and normal lymphocytes treated by the three ingredients. The various effects of the three compounds on HL-60 cells were respectively evaluated by agarose gel electrophoresis, ESR and immunohistochemical me(thods.) Results: These compounds effectively inhibited the proliferation of HL-60 cells and induced apoptosis which was determined by apoptotic changes in morphology and nuclear DNA degradation. Whereas no inhibition effects on normal lymphocytes were observed. In addition, the results of ESR showed that the activity of oxygen radical within HL-60 cells treated with there compounds decreased to trace level. Furthermore, in the immunohistochemical experiments, we found that the level of p45/skp2 in HL-60 cells decreased while the level of p27/kip increased. Conclusion: The taurine, ornithine and carnosine compounds can selectively suppress tumor cells proliferation by regulating the level of cell cycle proteins.

【关键词】 牛磺酸鸟氨酸肌肽细胞凋亡HL-60细胞
【Key words】 taurineornithinecarnosineapoptosisHL-60 cells
【基金】 国家自然科学基金重点项目(39730270)
  • 【文献出处】 中国应用生理学杂志 ,Chinese Journal of Applied Physiology , 编辑部邮箱 ,2005年02期
  • 【分类号】R733.7
  • 【被引频次】3
  • 【下载频次】109
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