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Inhibition of protein synthesis: a basis for tunicamycin-induced decrease in rat liver cytochrome P-450.

Y Singh·V Shirhatti·C T Liu·D R Feller·G Krishna
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Abstract

Tunicamycin caused a dose and time dependent decrease in cytochrome P-450 in rat liver. A dose of 50 micrograms/kg caused a decrease of about 50% in 72 hours. A similar decrease in the activities of rat liver microsomal aniline hydroxylase, aminopyrine N-demethylase and ethoxycoumarin O-deethylase were also seen after the tunicamycin treatment. Tunicamycin also suppressed food and water intake but the decrease in cytochrome P-450 was not related to these effects. NADPH cytochrome c reductase was not markedly decreased by tunicamycin. A decrease in cytochrome P-450 was also observed in cultured rat hepatocytes treated with tunicamycin. It decreased incorporation of [35S]-methionine into total proteins as well as into various cytochrome P-450 isozymes of rat hepatocytes. This indicates that a decrease in protein synthesis may be responsible for the tunicamycin-induced decrease in cytochrome P-450 and drug metabolism.

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AnimalsCells, CulturedCytochrome P-450 Enzyme SystemDose-Response Relationship, DrugGlucosamineLiverMaleMicrosomes, LiverNADH DehydrogenaseRatsRats, Inbred StrainsTime FactorsTunicamycinJournal Article

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Y Singh, V Shirhatti, C T Liu, D R Feller, G Krishna. 1985-10-14. Inhibition of protein synthesis: a basis for tunicamycin-induced decrease in rat liver cytochrome P-450.. https://doi.org/10.1016/0024-3205(85)90080-3

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