title: Effect of SOD1 overexpression on age- and noise-related hearing loss.
abstract: Reactive oxygen species (ROS) have been implicated in hearing loss associated with aging and noise exposure. Superoxide dismutases (SODs) form a first line of defense against damage mediated by the superoxide anion, the most common ROS. Absence of Cu/Zn SOD (SOD1) has been shown to potentiate hearing loss related to noise exposure and age. Conversely, overexpression of SOD1 may be hypothesized to afford a protection from age- and noise-related hearing loss. This hypothesis may be tested using a transgenic mouse model carrying the human SOD1 gene. Contrary to expectations, here, we report that no protection against age-related hearing loss was observed in mice up to 7 months of age or from noise-induced hearing loss when 8 week old mice were exposed to broadband noise (4-45 kHz, 110 dB for 1 h). Mitochondrial DNA deletion, an index of aging, was elevated in the acoustic nerve of transgenic mice compared to nontransgenic littermates. The results indicate the complexity of oxidative metabolism in the cochlea is greater than previously hypothesized.
authors.affiliation: Laboratory of Molecular Otology, Epstein Laboratories, Department of Otolaryngology-Head and Neck Surgery, University of California San Francisco, San Francisco, CA 94143-0526, USA.
authors.forename: Donald E
authors.initials: DE
authors.lastname: Coling
authors.forename: Kenneth C Y
authors.initials: KC
authors.lastname: Yu
authors.forename: David
authors.initials: D
authors.lastname: Somand
authors.forename: Bulent
authors.initials: B
authors.lastname: Satar
authors.forename: Uma
authors.initials: U
authors.lastname: Bai
authors.forename: Ting-Ting
authors.initials: TT
authors.lastname: Huang
authors.forename: Michael D
authors.initials: MD
authors.lastname: Seidman
authors.forename: Charles J
authors.initials: CJ
authors.lastname: Epstein
authors.forename: Anand N
authors.initials: AN
authors.lastname: Mhatre
authors.forename: Anil K
authors.initials: AK
authors.lastname: Lalwani
mesh_terms: D000367:Age Factors; D000375:Aging; D000818:Animals; D004272:DNA, Mitochondrial / Q000235:genetics; D005609:Free Radicals; D017353:Gene Deletion; D034381:Hearing Loss / Q000235:genetics*; D006317:Hearing Loss, Noise-Induced / Q000235:genetics*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009622:Noise; D018384:Oxidative Stress; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors; D014018:Tissue Distribution
chemical_list: D004272:DNA, Mitochondrial; D005609:Free Radicals; D013482:Superoxide Dismutase