Biomaterial Database

Cellular toxicity of aminoglycoside antibiotics in G418-sensitive and -resistant LLC-PK1 cells. 1994

M Takano, and M Okuda, and M Yasuhara, and R Hori

Department of Pharmacy, Kyoto University Hospital, Faculty of Medicine, Japan.

The effects of gentamicin and G418 on the cellular function of LLC-PK1 epithelial pig kidney cells were investigated. Exposing the cells for 2 days to these aminoglycoside antibiotics inhibited the increase in cell-associated apical membrane enzyme activity (alkaline phosphatase, aminopeptidase, and gamma-glutamyltransferase). Kinetic analysis revealed that the maximal activity of alkaline phosphatase was reduced by these aminoglycosides. Both aminoglycosides inhibited [3H]leucine incorporation into microsomes prepared from LLC-PK1 cells. The LLC-PK1 cells transfected with DNA encoding aminoglycoside 3'-phosphotransferase II, designated T2000B, were resistant to G418 as assessed by colony formation assay and the number of floating dead cells and by assay of apical enzyme activity. After a 4-hr exposure to G418, [3H]leucine incorporation in the host LLC-PK1 cells was inhibited, whereas that in T2000B cells was relatively unaffected. Gentamicin inhibited [3H]leucine incorporation similarly in both cells. The inhibition of protein synthesis by aminoglycosides occurred earlier than that of apical enzyme activity. These findings suggest that the inhibition of protein synthesis by aminoglycoside antibiotics is a possible cause of the reduction in cell viability as well as the apical enzymes in LLC-PK1 cells.

UI	MeSH Term	Description	Entries
D007668	Kidney	Body organ that filters blood for the secretion of URINE and that regulates ion concentrations.	Kidneys
D007930	Leucine	An essential branched-chain amino acid important for hemoglobin formation.	L-Leucine,Leucine, L-Isomer,L-Isomer Leucine,Leucine, L Isomer
D008861	Microsomes	Artifactual vesicles formed from the endoplasmic reticulum when cells are disrupted. They are isolated by differential centrifugation and are composed of three structural features: rough vesicles, smooth vesicles, and ribosomes. Numerous enzyme activities are associated with the microsomal fraction. (Glick, Glossary of Biochemistry and Molecular Biology, 1990; from Rieger et al., Glossary of Genetics: Classical and Molecular, 5th ed)	Microsome
D010957	Plasmids	Extrachromosomal, usually CIRCULAR DNA molecules that are self-replicating and transferable from one organism to another. They are found in a variety of bacterial, archaeal, fungal, algal, and plant species. They are used in GENETIC ENGINEERING as CLONING VECTORS.	Episomes,Episome,Plasmid
D002460	Cell Line	Established cell cultures that have the potential to propagate indefinitely.	Cell Lines,Line, Cell,Lines, Cell
D003513	Cycloheximide	Antibiotic substance isolated from streptomycin-producing strains of Streptomyces griseus. It acts by inhibiting elongation during protein synthesis.	Actidione,Cicloheximide
D004352	Drug Resistance, Microbial	The ability of microorganisms, especially bacteria, to resist or to become tolerant to chemotherapeutic agents, antimicrobial agents, or antibiotics. This resistance may be acquired through gene mutation or foreign DNA in transmissible plasmids (R FACTORS).	Antibiotic Resistance,Antibiotic Resistance, Microbial,Antimicrobial Resistance, Drug,Antimicrobial Drug Resistance,Antimicrobial Drug Resistances,Antimicrobial Resistances, Drug,Drug Antimicrobial Resistance,Drug Antimicrobial Resistances,Drug Resistances, Microbial,Resistance, Antibiotic,Resistance, Drug Antimicrobial,Resistances, Drug Antimicrobial
D005839	Gentamicins	A complex of closely related aminoglycosides obtained from MICROMONOSPORA purpurea and related species. They are broad-spectrum antibiotics, but may cause ear and kidney damage. They act to inhibit PROTEIN BIOSYNTHESIS.	Gentamicin Sulfate (USP),Gentamycin,G-Myticin,Garamycin,Gentacycol,Gentamicin,Gentamicin Sulfate,Gentamycins,Gentavet,Genticin,G Myticin,GMyticin,Sulfate, Gentamicin
D000469	Alkaline Phosphatase	An enzyme that catalyzes the conversion of an orthophosphoric monoester and water to an alcohol and orthophosphate. EC 3.1.3.1.
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia