Aminoglycosides suppress tRNA processing in human epidermal keratinocytes in vitro.
The ever-growing resistance of pathogens to antibiotics and the lack of potent antibacterial drugs constitute major problems in the treatment of infectious diseases. Thus, the better understanding of the mode of action of antibiotics at the molecular level is of essential importance. Accumulating evidence points towards RNA as being a crucial target of antibacterial and antiviral drugs. Interestingly, aminoglycosides, one of the most important families of antibiotics, apart from their inhibitory effect on ribosome function, reportedly interfere with various RNA molecules and in vitro suppress the proliferation of human keratinocytes. In this study we investigated the effect of the aminoglycosides neomycin B, paromomycin, tobramycin and gentamycin on ribonuclease P activity from normal human epidermal keratinocytes. All aminoglycosides tested revealed a dose-dependent inhibition of tRNA maturation, which was reduced by increasing Mg(2+) ion concentrations, indicating competition of the cationic aminoglycosides with magnesium ions required for catalysis. Our in vitro findings suggest that the inhibitory effects of aminoglycosides on tRNA processing may be implicated in the mechanisms of their antiproliferative action on human epidermal keratinocytes.
Tekos
A
A
Department of Biochemistry, School of Medicine, University of Patras, Patras, Greece.
Prodromaki
E
E
Papadimou
E
E
Pavlidou
D
D
Tsambaos
D
D
Drainas
D
D
D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000494:pharmacology*; D002240:Carbohydrate Sequence; D002474:Cell-Free System; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004722:Endoribonucleases / Q000037:antagonists & inhibitors; D000078404:Epidermal Cells; D004817:Epidermis / Q000187:drug effects* / Q000378:metabolism; D005839:Gentamicins / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects* / Q000378:metabolism; D008274:Magnesium / Q000737:chemistry / Q000494:pharmacology; D008969:Molecular Sequence Data; D009355:Neomycin / Q000737:chemistry / Q000494:pharmacology; D010303:Paromomycin / Q000737:chemistry / Q000494:pharmacology; D016337:RNA, Catalytic / Q000037:antagonists & inhibitors; D012343:RNA, Transfer / Q000037:antagonists & inhibitors* / Q000378:metabolism; D043262:Ribonuclease P; D013329:Structure-Activity Relationship; D014031:Tobramycin / Q000737:chemistry / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D005839:Gentamicins; D016337:RNA, Catalytic; D010303:Paromomycin; D012343:RNA, Transfer; D004722:Endoribonucleases; C468368:RPP14 protein, human; D043262:Ribonuclease P; D009355:Neomycin; D008274:Magnesium; D014031:Tobramycin