Unité de Génétique et Physiologie de l'Audition, Institut Pasteur, 75015 Paris, France; UMRS 1120, Institut National de la Santé et de la Recherche Médicale (INSERM), 75015 Paris, France; Sorbonne Universités, UPMC Université Paris 06, Complexité du Vivant, 75005 Paris, France.
UMRS 1120, Institut National de la Santé et de la Recherche Médicale (INSERM), 75015 Paris, France; Sorbonne Universités, UPMC Université Paris 06, Complexité du Vivant, 75005 Paris, France; Syndrome de Usher et Autres Atteintes Rétino-Cochléaires, Institut de la Vision, 75012 Paris, France.
Cell. 2015 Nov 5;163(4):894-906. doi: 10.1016/j.cell.2015.10.023.
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.
一种未知功能的蛋白质 pejvakin 的缺乏会导致一种非常异质的人类耳聋形式。Pejvakin 缺陷型（Pjvk(-/-)）小鼠也表现出可变的听觉表型。它们的听力阈值与每笼幼仔数量之间的相关性表明幼仔发声可能具有有害影响。直接声音或电刺激表明 Pjvk(-/-) 小鼠和患者的耳蜗感觉毛细胞和听觉通路神经元对声音特别敏感。亚细胞分析表明，pejvakin 与过氧化物酶体相关，是过氧化物酶体增殖所必需的。Pjvk(-/-)耳蜗显示出明显的氧化应激特征和抗氧化防御受损的特征，并且听觉起始后 Pjvk(-/-) 毛细胞中的过氧化物酶体显示出结构异常。噪声暴露会迅速上调野生型小鼠耳蜗中的 Pjvk 转录，并触发毛细胞和初级听觉神经元中的过氧化物酶体增殖。我们的结果表明，过氧化物酶体的抗氧化活性可保护听觉系统免受噪声引起的损伤。
