Hypervulnerability to Sound Exposure through Impaired Adaptive Proliferation of Peroxisomes.
Cell
; 163(4): 894-906, 2015 Nov 05.
Article
en En
| MEDLINE
| ID: mdl-26544938
ABSTRACT
A deficiency in pejvakin, a protein of unknown function, causes a strikingly heterogeneous form of human deafness. Pejvakin-deficient (Pjvk(-/-)) mice also exhibit variable auditory phenotypes. Correlation between their hearing thresholds and the number of pups per cage suggest a possible harmful effect of pup vocalizations. Direct sound or electrical stimulation show that the cochlear sensory hair cells and auditory pathway neurons of Pjvk(-/-) mice and patients are exceptionally vulnerable to sound. Subcellular analysis revealed that pejvakin is associated with peroxisomes and required for their oxidative-stress-induced proliferation. Pjvk(-/-) cochleas display features of marked oxidative stress and impaired antioxidant defenses, and peroxisomes in Pjvk(-/-) hair cells show structural abnormalities after the onset of hearing. Noise exposure rapidly upregulates Pjvk cochlear transcription in wild-type mice and triggers peroxisome proliferation in hair cells and primary auditory neurons. Our results reveal that the antioxidant activity of peroxisomes protects the auditory system against noise-induced damage.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Proteínas
/
Peroxisomas
/
Pérdida Auditiva Provocada por Ruido
/
Proteínas del Tejido Nervioso
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Cell
Año:
2015
Tipo del documento:
Article
País de afiliación:
Francia