Inhibition of Apical Membrane Enzyme Activities and Protein Synthesis by Gentamicin in a Kidney Epithelial Cell Line LLC-PK_1

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The mechanism of a gentamicin-induced decrease in apical membrane enzyme activities was investigated in LLC-PK_1 cells. Increasing activities of apical membrane enzymes (alkaline phosphatase, aminopeptidase, and γ-glutamyltransferase) were mrkedly suppressed by gentamicin during growth in culture. On the other hand, a lesser effect was observed when the activities of these enzymes were decreasing or relatively constant. Gentamicin treatment decreased the maximal enzyme activities of alkaline phosphatase and aminopeptidasem indicating that the number of active enzyme molecules in the apical membrane was decreased by gentamicim. [^3H]Leucine incorporation in LLC-PK_1 cells was inhibited by gentamicin in a dose-dependent manner, followed by a reduction of total protein. In addition, a well-known protein synthesis inhibitor, cycloheximide, also decreased the apical enzyme activities. These results suggest that the inhibition of protein synthesis by gentamicin is a possible cause of the decreased activities of apical membrane enzymes in LLC-PK_1 cells. The inhibition of protein synthesis may be related to the nephrotoxicity induced by aminoglycoside antibiotics.
公益社団法人日本薬学会の論文
1992-12-25