The redox protein p66(shc) mediates cochlear vascular dysfunction and transient noise-induced hearing loss

Anna Rita Fetoni, Fabiola Paciello, Gaetano Paludetti, Giovambattista Pani, Rolando Rolesi, Daniela Maria Samengo, Diana Troiani

Risultato della ricerca: Contributo in rivistaArticolo in rivistapeer review

11 Citazioni (Scopus)

Abstract

p66(shc), a member of the ShcA protein family, is essential for cellular response to oxidative stress, and elicits the formation of mitochondrial Reactive Oxygen Species (ROS), thus promoting vasomotor dysfunction and inflammation. Accordingly, mice lacking the p66 isoform display increased resistance to oxidative tissue damage and to cardiovascular disorders. Oxidative stress also contributes to noise-induced hearing loss (NIHL); we found that p66(shc) expression and serine phosphorylation were induced following noise exposure in the rat cochlea, together with markers of oxidative stress, inflammation and ischemia as indicated by the levels of the hypoxic inducible factor (HIF) and the vascular endothelial growth factor (VEGF) in the highly vascularised cochlear lateral region and spiral ganglion. Importantly, p66(shc) knock-out (p66 KO) 126 SvEv adult mice were less vulnerable to acoustic trauma with respect to wild type controls, as shown by preserved auditory function and by remarkably lower levels of oxidative stress and ischemia markers. Of note, decline of auditory function observed in 12 month old WT controls was markedly attenuated in p66KO mice consistent with delayed inner ear senescence. Collectively, we have identified a pivotal role for p66(shc) -induced vascular dysfunction in a common pathogenic cascade shared by noise-induced and age-related hearing loss.
Lingua originaleEnglish
pagine (da-a)25450-N/A
RivistaScientific Reports
Volume6
DOI
Stato di pubblicazionePubblicato - 2016

Keywords

  • Noise
  • ROS
  • aging
  • cochlea
  • hypoxia
  • inflammation
  • p66shc
  • vascular dysfunction

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