...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Biochemistry >Control of P-Glycoprotein Activity by Membrane Cholesterol Amounts and Their Relation to Multidrug Resistance in Human CEM Leukemia Cells
【24h】

Control of P-Glycoprotein Activity by Membrane Cholesterol Amounts and Their Relation to Multidrug Resistance in Human CEM Leukemia Cells

机译：膜胆固醇水平控制P-糖蛋白活性及其与人CEM白血病细胞多药耐药性的关系

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

P-glycoprotein(P-gp)is the most well-known ATP-binding cassette(ABC)transporter involved in unidirectional substrate translocation across the membrane lipid bilayer,thereby causing the typical multidrug resistance(MDR)phenotype expressed in many cancers.We observed that in human CEM acute lymphoblastic leukemia cells expressing various degrees of chemoresistance and where P-gp was the sole MDR-related ABC transporter detected,the amount of esterified cholesterol increased linearly with the level of resistance to vinblastine while the amounts of total and free cholesterol increased in a nonlinear way.Membrane cholesterol controlled the ATPase activity of P-gp in a linear manner,whereas the P-gp-induced daunomycin efflux decreased nonlinearly with the depletion of membrane cholesterol.All these elements suggest that cholesterol controls both the ATPase and the drug efflux activities of P-gp.In addition,in CEM cell lines that expressed increasing levels of elevated chemoresistance,the amount of P-gp increases to a plateau value of 40% of the total membrane proteins and remained unvaried while the amount of membrane cholesterol increased with the elevation of the MDR level,strongly suggesting that cholesterol may be directly involved in the typical MDR phenotype.Finally,we showed that the decreased daunomycin efflux by P-gp due to the partial depletion of membrane cholesterol was responsible for the efficient chemosensitization of resistant CEM cells,which could be totally reversed after cholesterol repletion.
机译：P-糖蛋白（P-gp）是最著名的ATP结合盒（ABC）转运蛋白，参与跨膜脂质双层的单向底物转运，从而导致在许多癌症中表现出典型的多药耐药性（MDR）表型。在人类CEM急性淋巴细胞白血病细胞中表现出不同程度的化学抗性，并且在检测到P-gp是唯一与MDR相关的ABC转运蛋白的过程中，酯化胆固醇的量与长春碱的抗性水平呈线性增加，而总胆固醇和游离胆固醇的量呈线性增加膜胆固醇以线性方式控制P-gp的ATPase活性，而P-gp诱导的道诺霉素外排随膜胆固醇的消耗而非线性地降低。所有这些因素表明，胆固醇同时控制着ATPase和此外，在表达高水平化学抗性的CEM细胞系中， P-gp的水平升高到总膜蛋白的40％的平稳值，并且保持不变，而膜胆固醇的量随MDR水平的升高而增加，这强烈表明胆固醇可能直接参与典型的MDR表型。最后，我们表明，由于膜胆固醇的部分耗尽，P-gp导致的道诺霉素外流减少是耐药CEM细胞高效化学增敏的原因，在补充胆固醇后可以完全逆转。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号