Inhibition of apical membrane enzyme activities and protein synthesis by gentamicin in a kidney epithelial cell line LLC-PK1.
The mechanism of a gentamicin-induced decrease in apical membrane enzyme activities was investigated in LLC-PK1 cells. Increasing activities of apical membrane enzymes (alkaline phosphatase, aminopeptidase, and gamma-glutamyltransferase) were markedly 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 aminopeptidase, indicating that the number of active enzyme molecules in the apical membrane was decreased by gentamicin. [3H]Leucine incorporation in LLC-PK1 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-PK1 cells. The inhibition of protein synthesis may be related to the nephrotoxicity induced by aminoglycoside antibiotics.
Okuda
M
M
Department of Pharmacy, Kyoto University Hospital, Faculty of Medicine, Kyoto University, Japan.
Takano
M
M
Yasuhara
M
M
Hori
R
R
D000818:Animals; D002460:Cell Line; D002462:Cell Membrane / Q000187:drug effects / Q000201:enzymology; D004847:Epithelial Cells; D004848:Epithelium / Q000187:drug effects / Q000201:enzymology; D005839:Gentamicins / Q000494:pharmacology*; D007668:Kidney / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D008565:Membrane Proteins / Q000037:antagonists & inhibitors* / Q000096:biosynthesis*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology*; D013552:Swine
D005839:Gentamicins; D008565:Membrane Proteins; D011500:Protein Synthesis Inhibitors