ERK2 mediates inner hair cell survival and decreases susceptibility to noise-induced hearing loss

Sci Rep. 2015 Nov 18:5:16839. doi: 10.1038/srep16839.

Abstract

Extracellular signal-regulated kinase (ERK) is a member of the family of mitogen-activated protein kinases (MAPKs) and coordinately regulates a multitude of cellular processes. In response to a variety of extracellular stimuli, phosphorylation of both threonine and tyrosine residues activates ERK. Recent evidence indicates that ERK is activated in response to cellular stress such as acoustic trauma. However, the specific role of ERK isoforms in auditory function is not fully understood. Here, we show that the isoform ERK2 plays an important role in regulating hair cell (HC) survival and noise-induced hearing loss (NIHL) in mice (C57BL/6J). We found that conditional knockout mice deficient for Erk2 in the inner ear HCs had hearing comparable to control mice and exhibited no HC loss under normal conditions. However, we found that these knockout mice were more vulnerable to noise and had blunted recovery from NIHL compared to control mice. Furthermore, we observed a significantly lower survival rate of inner hair cells in these mice compared to control mice. Our results indicate that ERK2 plays important roles in the survival of HC in NIHL.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Survival / genetics
  • Cochlea / metabolism
  • Cochlea / pathology
  • Disease Models, Animal
  • Disease Susceptibility*
  • Gene Expression
  • Hair Cells, Auditory, Inner / metabolism*
  • Hearing Loss, Noise-Induced / genetics*
  • Hearing Loss, Noise-Induced / metabolism*
  • Hearing Loss, Noise-Induced / physiopathology
  • Immunohistochemistry
  • Mice
  • Mice, Transgenic
  • Mitogen-Activated Protein Kinase 1 / genetics*
  • Mitogen-Activated Protein Kinase 1 / metabolism*
  • Mitogen-Activated Protein Kinase 3 / metabolism
  • Noise / adverse effects
  • Phosphorylation

Substances

  • Mapk1 protein, mouse
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3