title: Mitochondrial peroxiredoxin 3 regulates sensory cell survival in the cochlea.
abstract: This study delineates the role of peroxiredoxin 3 (Prx3) in hair cell death induced by several etiologies of acquired hearing loss (noise trauma, aminoglycoside treatment, age). In vivo, Prx3 transiently increased in mouse cochlear hair cells after traumatic noise exposure, kanamycin treatment, or with progressing age before any cell loss occurred; when Prx3 declined, hair cell loss began. Maintenance of high Prx3 levels via treatment with the radical scavenger 2,3-dihydroxybenzoate prevented kanamycin-induced hair cell death. Conversely, reducing Prx3 levels with Prx3 siRNA increased the severity of noise-induced trauma. In mouse organ of Corti explants, reactive oxygen species and levels of Prx3 mRNA and protein increased concomitantly at early times of drug challenge. When Prx3 levels declined after prolonged treatment, hair cells began to die. The radical scavenger p-phenylenediamine maintained Prx3 levels and attenuated gentamicin-induced hair cell death. Our results suggest that Prx3 is up-regulated in response to oxidative stress and that maintenance of Prx3 levels in hair cells is a critical factor in their susceptibility to acquired hearing loss.
authors.affiliation: Department of Pathology and Laboratory Medicine, Medical University of South Carolina, Charleston, South Carolina, United States of America.
authors.forename: Fu-Quan
authors.initials: FQ
authors.lastname: Chen
authors.forename: Hong-Wei
authors.initials: HW
authors.lastname: Zheng
authors.forename: Jochen
authors.initials: J
authors.lastname: Schacht
authors.forename: Su-Hua
authors.initials: SH
authors.lastname: Sha
mesh_terms: D000818:Animals; D016923:Cell Death; D002470:Cell Survival / Q000235:genetics*; D016166:Free Radical Scavengers / Q000494:pharmacology; D005786:Gene Expression Regulation; D005839:Gentamicins; D006198:Hair Cells, Auditory / Q000378:metabolism* / Q000473:pathology; D006319:Hearing Loss, Sensorineural / Q000139:chemically induced / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D018398:Homeodomain Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D062385:Hydroxybenzoates / Q000494:pharmacology; D007612:Kanamycin; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D009622:Noise; D018384:Oxidative Stress; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D012720:Severity of Illness Index
chemical_list: D016166:Free Radical Scavengers; D005839:Gentamicins; D018398:Homeodomain Proteins; D062385:Hydroxybenzoates; D034741:RNA, Small Interfering; C484663:Shox2 protein, mouse; D007612:Kanamycin; C009135:2,3-dihydroxybenzoic acid