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肝素6位羧基修饰对抑制P?鄄选择素介导的A375细胞粘附活性的影响
引用本文:魏 民,田美红,陈 琳,曾宪录.肝素6位羧基修饰对抑制P?鄄选择素介导的A375细胞粘附活性的影响[J].生物化学与生物物理进展,2006,33(1):72-76.
作者姓名:魏 民  田美红  陈 琳  曾宪录
作者单位:1. 东北师范大学生命科学学院,长春,130024
2. 东北师范大学体育学院,长春,130024
3. 长春市中心血站,长春,130033
基金项目:重庆市应用基础研究基金;中国科学院资助项目
摘    要:已有的研究表明,肝素可以作为P-选择素的配体,显著抑制肿瘤转移过程中P-选择素介导的肿瘤细胞与血小板间的粘附.但是,肝素被P-选择素识别所必需的确切寡糖结构信息仍很缺乏.通过选择性化学修饰方法制备了2种低抗凝血肝素衍生物,即羧基还原肝素(CR-肝素)和羧基还原后再硫酸化肝素(SCR-肝素),系统地研究了它们对P-选择素介导的A375细胞粘附的抑制.研究结果表明,显著失去抗凝血活性的CR-肝素仍能有效地抑制P-选择素介导的A375细胞粘附,说明肝素的C6羧基并不是被P-选择素识别所必需的.而SCR-肝素所发生的C6羧基向羟甲硫酸酯基的转化却显著降低了抗粘附活性,说明P-选择素对肝素的识别并不只依赖于肝素的电荷密度.研究结果为深入阐明拮抗P-选择素介导的肿瘤细胞粘附的分子机制提供了有价值的实验基础.

关 键 词:肝素  羧基还原肝素  P-选择素  血小板  肿瘤细胞粘附
收稿时间:2005-06-24
修稿时间:2005-06-242005-09-10

Effects of The Modification of Heparin 6-Carboxyl Group on Inhibitive Activity of P-Selectin-mediated A375 Cells Adhesion
WEI Min,Tian Mei-Hong,CHEN Lin and Zeng Xian-Lu.Effects of The Modification of Heparin 6-Carboxyl Group on Inhibitive Activity of P-Selectin-mediated A375 Cells Adhesion[J].Progress In Biochemistry and Biophysics,2006,33(1):72-76.
Authors:WEI Min  Tian Mei-Hong  CHEN Lin and Zeng Xian-Lu
Institution:School of Life Sciences, Northeast Normal University, Changchun 130024, China;School of Physical Education, Northeast Normal University, Changchun 130024, China;Changchun Blood Center, Changchun 130033, China;School of Life Sciences, Northeast Normal University, Changchun 130024, China
Abstract:Several studies have demonstrated that heparin can significantly inhibit the P-selectin-mediated interaction of platelets and tumor cells during metastasis as a P-selectin ligand. However, little information is available about the specific oligosaccharide structures of heparin in recognition by P-selectin. Two chemically modified heparins, CR-heparin and SCR-heparin were prepared, to explore if such heparin derivatives can reduce the P-selectin-mediated A375 tumor cell adhesion. The results indicated that CR-heparin with low anticoagulant activity could significantly inhibit the P-selectin-mediated A375 tumor cell adhesion, demonstrating that 6-carboxyl group of the glucuronic acid in heparin may not be crucial for recognizing by P-selectin. In contrast, SCR-heparin reduced the inhibiting activity dramatically, suggesting that the recognition of P-selectin to heparin depend on not only densities of negative charge. These results provide valuable experimental evidence for clarifying the molecular mechanism of P-selectin-mediated tumor cell adhesion.
Keywords:heparin  carboxyl-reduced heparin  P-selectin  platelet  tumor cell adhesion
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