Intracellular mechanisms of aminoglycoside-induced cytotoxicity

Takatoshi Karasawa, Peter S. Steyger

Research output: Contribution to journalReview articlepeer-review

43 Scopus citations

Abstract

Since introduction into clinical practice over 60 years ago, aminoglycoside antibiotics remain important drugs in the treatment of bacterial infections, cystic fibrosis and tuberculosis. However, the ototoxic and nephrotoxic properties of these drugs are still a major clinical problem. Recent advances in molecular biology and biochemistry have begun to uncover the intracellular actions of aminoglycosides that lead to cytotoxicity. In this review, we discuss intracellular binding targets of aminoglycosides, highlighting specific aminoglycoside-binding proteins (HSP73, calreticulin and CLIMP-63) and their potential for triggering caspases and Bcl-2 signalling cascades that are involved in aminoglycoside-induced cytotoxicity. We also discuss potential strategies to reduce aminoglycoside cytotoxicity, which are necessary for greater bactericidal efficacy during aminoglycoside pharmacotherapy.

Original languageEnglish (US)
Pages (from-to)879-886
Number of pages8
JournalIntegrative Biology
Volume3
Issue number9
DOIs
StatePublished - Sep 2011

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry

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