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Eur J Cell Biol. 1987 Feb;43(1):141-7.

Aminoglycoside antibiotic treatment of human fibroblasts: intracellular accumulation, molecular changes and the loss of ribosomal accuracy.


The aminoglycoside antibiotic, G418, was rapidly endocytosed by human fibroblasts. The endocytic uptake comprised two phases. A rapid phase in which G418 was first adsorbed to the cell surface, followed by a slower rate of uptake of 7 to 11 micrograms/mg cell protein/24 h. The rapid uptake was independent of temperature and a fluorescent derivative of G418 could be seen bound to the cell surface. This evidence suggests a nonspecific adsorption mechanism. The slower rate of accumulation may arise from fluid-phase pinocytosis. The effects of G418 and paromomycin on protein synthesis in vivo and in vitro were compared and it was concluded that G418 was more active on mammalian ribosomes. Finally, changes in the pattern of cellular proteins during treatment with either aminoglycoside were found only with G418. The changes in the pattern of proteins suggest the synthesis of stress proteins in treated cells. This change in pattern may be interpreted as a cellular response to abnormal protein synthesis arising from a loss of fidelity or some inhibitory function of G418 on membrane metabolism which may lead to a shortening of cellular life span.

[Indexed for MEDLINE]

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