Low Dose Oxidative Stress Induces Mitochondrial Damage in Hair Cells

Anat Rec (Hoboken). 2012 Nov;295(11):1868-76. doi: 10.1002/ar.22594. Epub 2012 Oct 8.

Abstract

Oxidative stress has been implicated as a cause of hair cell damage after ischemia reperfusion injury, noise trauma, and ototoxic injury. Oxidative stress can induce both apoptosis or necrosis depending on the degree of exposure. To study how reactive oxygen species (ROS) interacts with hair cells, we have developed an in vitro model of oxidative stress using organ of Corti cultures exposed to physiologically relevant concentrations of hydrogen peroxide (H(2) O(2) ). Treatment of organ of Corti cultures with low concentrations of H(2) O(2) results in loss of outer hair cells in the basal turn of the explant. Higher concentrations of peroxide result in more extensive outer hair cell injury as well as loss of inner hair cells. Early outer hair cell death appears to occur though apoptosis as demonstrated by staining of activated caspase. The effect of oxidative stress on mitochondrial function is a key determinant of degree of damage. Oxidative stress results in reduction of the mitochondrial membrane potential and reduction of mitochondrial produced antioxidants. Low doses of oxidative stress induce changes in mitochondrial gene expression and induce mitochondrial DNA deletions. Recurrent oxidative stress or inhibition of mitochondrial function significantly enhanced hair cell death. This tissue culture model of oxidative hair cell injury maintains a pattern of injury similar to what is observed in vivo after oxidative injury and can be used to study the effects of ROS on hair cells over the time period of the culture.

MeSH terms

  • Animals
  • Apoptosis*
  • Caspases / metabolism
  • Cells, Cultured
  • Enzyme Activation / drug effects
  • Hair Cells, Auditory / drug effects
  • Hair Cells, Auditory / metabolism
  • Hair Cells, Auditory / pathology*
  • Hydrogen Peroxide / pharmacology
  • Membrane Potential, Mitochondrial / drug effects
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred CBA
  • Mitochondria / metabolism
  • Mitochondria / pathology*
  • Mitochondrial Proteins / metabolism
  • Organ of Corti / metabolism
  • Organ of Corti / pathology*
  • Oxidants / pharmacology
  • Oxidation-Reduction
  • Oxidative Stress*
  • Protein Biosynthesis / drug effects
  • Reactive Oxygen Species / metabolism

Substances

  • Mitochondrial Proteins
  • Oxidants
  • Reactive Oxygen Species
  • Hydrogen Peroxide
  • Caspases