A molecular and cellular hypothesis for aminoglycoside-induced deafness.
The ototoxic effects of aminoglycoside antibiotics are well known. However, a molecular and cellular mechanism for the death of cochlear hair cells has remained difficult to prove. Human genetic studies have shown that a rare trait for hypersensitivity to aminoglycosides is conferred by mitochondrial genetic variation. Recently, a gene involved has been identified as the mitochondrial small ribosomal RNA gene, consistent with the known mechanism of aminoglycoside action against bacteria. We used the existing data as a basis for our hypothesis of a molecular and cellular model for aminoglycoside ototoxicity that is described in this paper.
Department of Molecular Pharmacology and Toxicology, School of Pharmacy, University of Southern California, Los Angeles 90033.
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Cortopassi
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Hutchin
D000617:Aminoglycosides / Q000009:adverse effects* / Q000235:genetics / Q000378:metabolism; D044466:Asian People / Q000235:genetics; D001483:Base Sequence; D003638:Deafness / Q000139:chemically induced / Q000209:etiology* / Q000235:genetics / Q000473:pathology; D004342:Drug Hypersensitivity / Q000150:complications / Q000235:genetics*; D005787:Gene Frequency; D006198:Hair Cells, Auditory / Q000187:drug effects*; D006801:Humans; D008954:Models, Biological; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D010375:Pedigree; D012335:RNA, Ribosomal / Q000737:chemistry / Q000235:genetics; D012336:RNA, Ribosomal, 16S / Q000737:chemistry / Q000235:genetics
D000617:Aminoglycosides; D012335:RNA, Ribosomal; D012336:RNA, Ribosomal, 16S; C075526:RNA, ribosomal, 12S