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

Authors
Journal
Life Sciences
0024-3205
Publisher
Elsevier
Publication Date
Volume
37
Issue
15
Identifiers
DOI: 10.1016/0024-3205(85)90080-3
Disciplines
  • Biology

Abstract

Abstract Tunicamycin caused a dose and time dependent decrease in cytochrome P-450 in rat liver. A dose of 50 μg/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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