Consiglio Nazionale delle Ricerche

Tipo di prodottoArticolo in rivista
TitoloCx26 partial loss causes accelerated presbycusis by redox imbalance and dysregulation of Nfr2 pathway
Anno di pubblicazione2018
FormatoElettronico
Autore/iFetoni A.R.; Zorzi V.; Paciello F.; Ziraldo G.; Peres C.; Raspa M.; Scavizzi F.; Salvatore A.M.; Crispino G.; Tognola G.; Gentile G.; Spampinato A.G.; Cuccaro D.; Guarnaccia M.; Morello G.; Van Camp G.; Fransen E.; Brumat M.; Girotto G.; Paludetti G.; Gasparini P.; Cavallaro S.; Mammano F.
Affiliazioni autoriCNR Institute of Cell Biology and Neurobiology, Monterotondo, 00015, Italy; Università Cattolica del Sacro Cuore, Largo F. Vito 1, Rome, 00168, Italy; Institute of Otolaryngology, Fondazione Policlinico Universitario A. Gemelli IRCCS, Largo F. Vito 1, Rome, 00168, Italy; Institute of Otolaryngology, Fondazione Policlinico Universitario A. Gemelli IRCCS, Largo F. Vito 1, Rome, 00168, Italy; CNR Institute of Electronics, Computer and Telecommunication Engineering, Milano, 20133, Italy; CNR Institute of Neurological Sciences, Catania, 95126, Italy; CNR Institute of Neurological Sciences, Catania, 95126, Italy; Center of Medical Genetics, University of Antwerp and Antwerp University Hospital, Universiteitsplein 1, Antwerp, 2610, Belgium; Center of Medical Genetics, University of Antwerp and Antwerp University Hospital, Universiteitsplein 1, Antwerp, 2610, Belgium; Center of Medical Genetics, University of Antwerp and Antwerp University Hospital, Universiteitsplein 1, Antwerp, 2610, Belgium; Department of Biomedical Sciences, University of Antwerp, Antwerp, 2650, Belgium; Dept Med Surg & Hlth Sci, University of Trieste, Trieste, Italy; IRCCS Burlo Garofolo, Inst Maternal & Child Hlth, Trieste, , Italy; University of Padova, Department of Physics and Astronomy "G. Galilei", Padova, , Italy; CNR Institute of Neurological Sciences, Via P. Gaifami 18, Catania, 95126, Italy; CNR Institute of Neurological Sciences, Via P. Gaifami 18, Catania, 95126, Italy; CNR Institute of Cell Biology and Neurobiology, Via E. Ramarini 32, Monterotondo, RM, 00015, Italy
Autori CNR e affiliazioni
  • VERONICA ZORZI
  • GIULIA CRISPINO
  • GIOVANNA MORELLO
  • DENIS CUCCARO
  • FABIOLA PACIELLO
  • ANNA RITA FETONI
  • CHIARA PERES
  • GAIA ZIRALDO
  • MARCELLO RASPA
  • SEBASTIANO CAVALLARO
  • GABRIELLA TOGNOLA
  • FABIO MAMMANO
  • MARIA GUARNACCIA
  • GIULIA GENTILE
  • ANTONIO GIANMARIA SPAMPINATO
  • ANNA MARIA SALVATORE
  • FERDINANDO SCAVIZZI
Lingua/e
  • inglese
AbstractMutations in GJB2, the gene that encodes connexin 26 (Cx26), are the most common cause of sensorineural hearing impairment. The truncating variant 35delG, which determines a complete loss of Cx26 protein function, is the prevalent GJB2 mutation in several populations. Here, we generated and analyzed Gjb2+/- mice as a model of heterozygous human carriers of 35delG. Compared to control mice, auditory brainstem responses (ABRs) and distortion product otoacoustic emissions (DPOAEs) worsened over time more rapidly in Gjb2+/- mice, indicating they were affected by accelerated age-related hearing loss (ARHL), or presbycusis. We linked causally the auditory phenotype of Gjb2+/- mice to apoptosis and oxidative damage in the cochlear duct, reduced release of glutathione from connexin hemichannels, decreased nutrient delivery to the sensory epithelium via cochlear gap junctions and deregulated expression of genes that are under transcriptional control of the nuclear factor erythroid 2-related factor 2 (Nrf2), a pivotal regulator of tolerance to redox stress. Moreover, a statistically significant genome-wide association with two genes (PRKCE and TGFB1) related to the Nrf2 pathway (p-value < 4 × 10-2) was detected in a very large cohort of 4091 individuals, originating from Europe, Caucasus and Central Asia, with hearing phenotype (including 1076 presbycusis patients and 1290 healthy matched controls). We conclude that (i) elements of the Nrf2 pathway are essential for hearing maintenance and (ii) their dysfunction may play an important role in the etiopathogenesis of human presbycusis.
Lingua abstractinglese
Altro abstract-
Lingua altro abstract-
Pagine da301
Pagine a317
Pagine totali-
RivistaRedoxBiology
Editore: Elsevier
ISSN: 2213-2317
Titolo chiave: RedoxBiology
Numero volume della rivista19
Fascicolo della rivista-
DOI10.1016/j.redox.2018.08.002
Verificato da referee-
Stato della pubblicazionePublished version
Indicizzazione (in banche dati controllate)
  • Scopus (Codice:2-s2.0-85053016962)
Parole chiaveAge-related hearing loss, Connexin 26, Mouse models, Genome-wide association study, Hair cells, Spiral ganglion neurons
Link (URL, URI)http://www.scopus.com/record/display.url?eid=2-s2.0-85053016962&origin=inward
Titolo parallelo-
Data di accettazione-
Note/Altre informazioni-
Strutture CNR
  • IEIIT — Istituto di elettronica e di ingegneria dell'informazione e delle telecomunicazioni
  • ISN — Istituto di scienze neurologiche
  • IBCN — Istituto di Biologia Cellulare e Neurobiologia
Moduli CNR-
Progetti Europei-
Allegati