首页> 外文期刊>Molecular and Cellular Biology >Chinese hamster cell mutant resistant to ML236B (Compactin) is defective in endocytosis of low-density lipo-protein.
【24h】

Chinese hamster cell mutant resistant to ML236B (Compactin) is defective in endocytosis of low-density lipo-protein.

机译:对ML236B(Compactin)有抗性的中国仓鼠细胞突变体在低密度脂蛋白的内吞作用方面存在缺陷。

获取原文
           

摘要

A fungal metabolite, ML236B (Compactin), isolated from Penicillium citrinum, is a specific inhibitor of 3-hydroxy-3-methylglutaryl (HMG)-coenzyme A reductase (EC 1.1.1.34). Three ML236B-resistant (ML236Br) mutants, MF-1, MF-2, and MF-3, were isolated from V79 after N-methyl-N'-nitro-N-nitrosoguanidine mutagenesis. The fluctuation test showed 2.2 X 10(-6) mutants per cell per generation of a spontaneous mutation frequency of ML236Br clones. These ML236Br clones showed a four- to fivefold-higher resistance to the drug than did their parental V79. Radioactive acetate, but not mevalonate, incorporation into the sterol fraction increased about 10-fold in ML236Br clones in comparison with that in V79. The cellular level of HMG-coenzyme A reductase in three ML236Br mutants was found to be a few-fold higher than that of V79 when cultured in the presence of lipoproteins. The 125I-labeled low-density lipoprotein-binding assay showed binding activity in three ML236Br clones comparable to that of the parental V79 cells. By contrast, an internalization assay of 125I-labeled low-density lipoprotein into the cells showed significantly reduced activity in three ML236Br clones in comparison with V79.
机译:从柠檬青霉分离的真菌代谢产物ML236B(Compactin)是3-羟基-3-甲基戊二烯基(HMG)-辅酶A还原酶(EC 1.1.1.34)的特异性抑制剂。 N-甲基-N'-硝基-N-亚硝基胍诱变后,从V79中分离出三个耐ML236B的(ML236Br)突变体MF-1,MF-2和MF-3。波动测试显示,每代ML236Br克隆的自发突变频率为每个细胞2.2 X 10(-6)个突变体。这些ML236Br克隆对药物的抗性比其亲本V79高四到五倍。与V79中相比,ML236Br克隆中放射性乙酸盐(而非甲羟戊酸盐)掺入固醇部分的含量增加了约10倍。当在脂蛋白存在下培养时,发现三个ML236Br突变体中HMG辅酶A还原酶的细胞水平比V79高几倍。 125I标记的低密度脂蛋白结合测定法显示了与亲代V79细胞相当的三个ML236Br克隆的结合活性。相比之下,与V79相比,将125I标记的低密度脂蛋白进入细胞的内部化分析表明,三个ML236Br克隆的活性大大降低。

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