Prosaposin-derived peptide alleviates ischaemia-induced hearing loss

Acta Otolaryngol. 2013 May;133(5):462-8. doi: 10.3109/00016489.2012.750430. Epub 2012 Dec 7.

Abstract

Conclusion: An 18-mer peptide derived from the neurotrophic region of prosaposin (PS-pep) prevents hearing loss and cochlear damage due to transient cochlear ischaemia by activating an anti-apoptotic pathway. PS-pep is a potent candidate molecule for alleviating ischaemia-induced hearing loss.

Objective: PS-pep was investigated for its protective effects against ischaemia-induced hearing loss and cochlear damage.

Methods: Ischaemia was induced in both cochleae in Mongolian gerbils by pulling the ligatures around both vertebral arteries in an anterior direction using 5 g weights for 15 min. PS-pep was synthesized artificially and administered subcutaneously four times after the induction of transient cochlear ischaemia.

Results: An increase in the auditory brainstem response threshold was alleviated in animals treated with 2.0 mg/kg PS-pep. Histological examinations conducted on day 7 showed that the loss of inner hair cells (IHCs) was more prominent than that of outer hair cells. Higher doses of PS-pep significantly alleviated IHC loss. An increase in the anti-apoptotic factor bcl-2 was also noted in the IHCs treated with PS-pep.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cochlea / blood supply*
  • Disease Models, Animal
  • Evoked Potentials, Auditory, Brain Stem
  • Gerbillinae
  • Hearing Loss / drug therapy*
  • Hearing Loss / etiology
  • Ischemia / complications*
  • Organ of Corti / metabolism
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Saposins / chemical synthesis
  • Saposins / therapeutic use*

Substances

  • PSAP protein, human
  • Proto-Oncogene Proteins c-bcl-2
  • Saposins