Enhancement of cytotoxicity of modeccin by nigericin in modeccin-resistant mutant cell lines.
We have isolated a Chinese hamster ovary cell mutant (DMPR-2) simultaneously resistant to diphtheria toxin and modeccin. In addition to the increased resistance to these two toxins used in the selection, this mutant is more resistant to Pseudomonas toxin and hypersensitive to ricin than the parental cell line. In contrast to the wild-type cells in which nigericin protects cells from modeccin, the cytotoxicity of modeccin in the DMPR-2 mutant is enhanced by nigericin. We have also studied the effects of nigericin and NH4Cl on the cytotoxicity of modeccin in a modeccin-resistant mutant of HeLa cells (ModRI). The cytotoxicity of modeccin is enhanced by nigericin in ModRI mutant cells, in contrast to the protection of modeccin cytotoxicity by nigericin in the parental HeLa cells. Our results suggest that modeccin can reach the cytosol of mammalian cells by two distinct routes; the major route requires endosomal acidification and the minor route is activated by nigericin.
Ghosh
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PC
Department of Microbiology, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814-4799.
Wu
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HC
D000643:Ammonium Chloride / Q000494:pharmacology; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001427:Bacterial Toxins / Q000494:pharmacology; D002460:Cell Line; D004167:Diphtheria Toxin / Q000494:pharmacology; D004351:Drug Resistance / Q000235:genetics; D004357:Drug Synergism; D006367:HeLa Cells; D006801:Humans; D007501:Iron / Q000378:metabolism; D037102:Lectins / Q000378:metabolism / Q000494:pharmacology*; D009154:Mutation; D009550:Nigericin / Q000494:pharmacology*; D037121:Plant Lectins; D014176:Protein Biosynthesis; D011549:Pseudomonas; D054790:Ribosome Inactivating Proteins, Type 2; D012276:Ricin / Q000378:metabolism / Q000494:pharmacology; D014118:Toxins, Biological / Q000494:pharmacology*; D014168:Transferrin / Q000378:metabolism
D000900:Anti-Bacterial Agents; D001427:Bacterial Toxins; D004167:Diphtheria Toxin; D037102:Lectins; D037121:Plant Lectins; D054790:Ribosome Inactivating Proteins, Type 2; D014118:Toxins, Biological; D014168:Transferrin; D000643:Ammonium Chloride; C016004:modeccin; D012276:Ricin; D007501:Iron; D009550:Nigericin