Loss of RAD6B induces degeneration of the cochlea in mice

Biochem Biophys Res Commun. 2020 Oct 20;531(3):402-408. doi: 10.1016/j.bbrc.2020.08.017. Epub 2020 Aug 28.

Abstract

Presbycusis is a form of age-related hearing loss (AHL). Many studies have shown that the degeneration of various structures in the cochlea of the inner ear is related to AHL, and DNA damage is an important factor leading to the above process. As an E2 ubiquitin-conjugated enzyme, RAD6B plays an important role in DNA damage repair (DDR) through histone ubiquitination. However, the molecular mechanism is still unclear. In this study, we investigated the role of RAD6B in the morphological changes and DDR mechanisms in aging-related degeneration of the cochlea of mice. We observed that the hair cells, stria vascularis and spiral ganglion in the cochlea of the RAD6B knockout mice showed significant degenerative changes and abnormal expression of proteins associated with DDR mechanisms compared with those of the littermate wild-type mice. In conclusion, our results suggest that the deletion of RAD6B may lead to abnormalities in DDR, thereby accelerating the degeneration of various structures in the cochlea and senescence and apoptosis of cochlea cells.

Keywords: Cochlea; DNA damage; Degeneration; RAD6B; Ubiquitin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / pathology*
  • Animals
  • Apoptosis
  • Caspase 3 / metabolism
  • Cell Line
  • Cochlea / metabolism*
  • Cochlea / pathology*
  • Cyclin-Dependent Kinase Inhibitor p16 / metabolism
  • Cyclin-Dependent Kinase Inhibitor p21 / metabolism
  • DNA Damage
  • DNA Repair
  • Histones / metabolism
  • Mice, Knockout
  • Tumor Suppressor Protein p53 / metabolism
  • Ubiquitin-Conjugating Enzymes / deficiency*
  • Ubiquitin-Conjugating Enzymes / metabolism

Substances

  • Cyclin-Dependent Kinase Inhibitor p16
  • Cyclin-Dependent Kinase Inhibitor p21
  • Histones
  • Tumor Suppressor Protein p53
  • gamma-H2AX protein, mouse
  • Ube2b protein, mouse
  • Ubiquitin-Conjugating Enzymes
  • Caspase 3