Hypervulnerability to Sound Exposure through Impaired Adaptive Proliferation of Peroxisomes

被引：158

作者：

Delmaghani, Sedigheh ^{[1
,2
,3
]}

Defourny, Jean ^{[1
,2
,3
]}

Aghaie, Asadollah ^{[2
,3
,4
]}

Beurg, Maryline ^{[5
]}

Dulon, Didier ^{[5
]}

Thelen, Nicolas ^{[6
]}

Perfettini, Isabelle ^{[1
,2
,3
]}

Zelles, Tibor ^{[7
,8
]}

Aller, Mate ^{[7
]}

Meyer, Anais ^{[1
,2
,3
]}

Emptoz, Alice ^{[1
,2
,3
]}

Giraudet, Fabrice ^{[9
,10
,11
]}

Leibovici, Michel ^{[1
,2
,3
]}

Dartevelle, Sylvie ^{[12
]}

Soubigou, Guillaume ^{[13
]}

Thiry, Marc ^{[6
]}

Vizi, E. Sylvester ^{[7
]}

Safieddine, Saaid ^{[1
,2
,3
]}

Hardelin, Jean-Pierre ^{[1
,2
,3
]}

Avan, Paul ^{[9
,10
,11
]}

Petit, Christine ^{[1
,2
,3
,14
]}

机构：

[1] Inst Pasteur, Unite Genet & Physiol Audit, F-75015 Paris, France

[2] INSERM, UMRS 1120, F-75015 Paris, France

[3] Univ Paris 06, Sorbonne Univ, Complex Vivant, F-75005 Paris, France

[4] Inst Vis, Syndrome Usher & Autres Atteintes Retino Cochleai, F-75012 Paris, France

[5] Univ Bordeaux, Equipe Neurophysiol Synapse Audit, Inst Neurosci, CHU Pellegrin, F-33076 Bordeaux, France

[6] Univ Liege, Unit Cell & Tissue Biol, GIGA Neurosci, CHU Sart Tilman, B-4000 Liege, Belgium

[7] Hungarian Acad Sci, Inst Expt Med, H-1083 Budapest, Hungary

[8] Semmelweis Univ, Dept Pharmacol & Pharmacotherapy, H-1089 Budapest, Hungary

[9] Univ Auvergne, Lab Biophys Sensorielle, F-63000 Clermont Ferrand, France

[10] INSERM, UMR 1107, F-63000 Clermont Ferrand, France

[11] Ctr Jean Perrin, F-63000 Clermont Ferrand, France

[12] Inst Pasteur, Plateforme Ingn Anticorps, F-75015 Paris, France

[13] Inst Pasteur, Plateforme Transcriptome & Epigenome, F-75015 Paris, France

[14] Coll France, F-75005 Paris, France

来源：

CELL | 2015年 / 163卷 / 04期

关键词：

HEARING-LOSS; MUTATIONS; PROTECTS; GENETICS; PEJVAKIN; CHANNELS; STRESS; INJURY;

D O I：

10.1016/j.cell.2015.10.023

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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 wildtype 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.

引用

页码：894 / 906

页数：13

共 30 条

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