Enhancement of the cytotoxicity of mistletoe lectin-1 (ML-1) by high pH or perturbation in Golgi functions.
We have studied the cytotoxicity of Mistletoe lectin-1 (ML-1), a cytotoxic protein produced by Viscum album, in CHO and V79 cells and in mutant cell lines altered in Golgi functions or in endosomal acidification. In wild-type CHO cells, cytotoxicity of ML-1 was greatly enhanced by ammonium chloride or nigericin. A CHO mutant defective in endosomal acidification (DMPR-2), which is resistant to diphtheria toxin, modeccin and Pseudomonas aeruginosa exotoxin A and hypersensitive to ricin, showed increased sensitivity to ML-1. MonR-31 and MF-1 are monensin- and compactin-resistant mutants derived from CHO and V79 cell lines, respectively, and are presumably altered in Golgi functions. The cytotoxicity of ML-1 was found to be increased in both MonR-31 and MF-1 cells as compared with their parental cells. These results indicate that the effects of chemicals or mutations altering endosomal acidification and Golgi functions on the cytotoxicity of ML-1 are similar to those on ricin cytotoxicity. Our results suggest that the cytotoxicity of ML-1 is enhanced by an increase in endosomal pH, as well as by chemicals or mutations altering the structure/functions of the Golgi regions. Like ricin, the intoxication process of ML-1 may involve the Golgi regions.
Yoshida
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T
Department of Microbiology, Uniformed Services University of the Health Sciences, Bethesda, Maryland.
Zhang
M
M
Chen
C
C
Franz
H
H
Wu
H C
HC
D000643:Ammonium Chloride / Q000494:pharmacology; D000818:Animals; D002470:Cell Survival / Q000187:drug effects*; D006224:Cricetinae; D003412:Cricetulus; D005260:Female; D006056:Golgi Apparatus / Q000187:drug effects*; D006863:Hydrogen-Ion Concentration; D009154:Mutation; D009550:Nigericin / Q000494:pharmacology; D010053:Ovary / Q000166:cytology; D028321:Plant Preparations; D010940:Plant Proteins; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D054790:Ribosome Inactivating Proteins, Type 2; D012276:Ricin / Q000633:toxicity; D014118:Toxins, Biological / Q000494:pharmacology*; D014709:Vero Cells / Q000187:drug effects
D028321:Plant Preparations; D010940:Plant Proteins; D054790:Ribosome Inactivating Proteins, Type 2; D014118:Toxins, Biological; C009674:ribosome inactivating protein, Viscum; D000643:Ammonium Chloride; D012276:Ricin; D009550:Nigericin