PUBLICATION

Response of mechanosensory hair cells of the zebrafish lateral line to aminoglycosides reveals distinct cell death pathways

Authors
Owens, K.N., Coffin, A.B., Hong, L.S., Bennett, K.O., Rubel, E.W., and Raible, D.W.
ID
ZDB-PUB-090319-6
Date
2009
Source
Hearing Research   253(1-2): 32-41 (Journal)
Registered Authors
Owens, Kelly, Raible, David
Keywords
Ototoxicity, Aminoglycoside, Hair cell, Mechanosensory, Lateral line, Zebrafish, Hair cell
MeSH Terms
  • Amiloride/pharmacology
  • Aminoglycosides/antagonists & inhibitors
  • Aminoglycosides/toxicity*
  • Animals
  • Anti-Bacterial Agents/antagonists & inhibitors
  • Anti-Bacterial Agents/toxicity
  • Cell Death/drug effects
  • Gentamicins/antagonists & inhibitors
  • Gentamicins/toxicity
  • Larva/cytology
  • Larva/drug effects
  • Lateral Line System/drug effects*
  • Lateral Line System/pathology*
  • Mechanoreceptors/drug effects*
  • Mechanoreceptors/pathology*
  • Mutation
  • Neomycin/antagonists & inhibitors
  • Neomycin/toxicity
  • Zebrafish/anatomy & histology
  • Zebrafish/genetics
PubMed
19285126 Full text @ Hear. Res.
Abstract
We report a series of experiments investigating the kinetics of hair cell loss in lateral line neuromasts of zebrafish larvae following exposure to aminoglycoside antibiotics. Comparisons of the rate of hair cell loss and the differential effects of acute versus chronic exposure to gentamicin and neomycin revealed markedly different results. Neomycin induced rapid and dramatic concentration-dependent hair cell loss that is essentially complete within 90 minutes, regardless of concentration or exposure time. Gentamicin induced loss of half of the hair cells within 90 minutes and substantial additional loss, which was prolonged and cumulative over exposure times up to at least 24 hr. Small molecules and genetic mutations that inhibit neomycin-induced hair cell loss were ineffective against prolonged gentamicin exposure supporting the hypothesis that these two drugs are revealing at least two cellular pathways. The mechanosensory channel blocker amiloride blocked both neomycin and gentamicin-induced hair cell death acutely and chronically indicating that these aminoglycosides share a common entry route. Further tests with additional aminoglycosides revealed a spectrum of differential responses to acute and chronic exposure. The distinctions between the times of action of these aminoglycosides indicate that these drugs induce multiple cell death pathways.
Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping