The Role of superoxide dismutase in age-related and noise-induced hearing loss: Clues from sod1 knockout mice

Sandra L. McFadden, Dalian Ding, Kevin Ohlemiller, Richard J. Salvi

Research output: Chapter in Book/Report/Conference proceedingChapterpeer-review

11 Scopus citations


The two most common causes of hearing loss in adults are (1) acoustic overexposure, resulting in noise-induced hearing loss (NIHL), and (2) age-related cochlear degeneration, resulting in age-related hearing loss (AHL), or presbycusis. The mechanisms underlying NIHL and AHL are not well understood. However, recent investigations implicate a common etiological factor in NIHL and AHL: an imbalance between levels of reactive oxygen species (ROS) produced during cellular metabolism, and the body’s defenses against them. Produced in excess of the body’s ability to remove them, ROS can cause extensive cellular damage. One important ROS is the superoxide radical (·O). Superoxide has many important functions in the body, but it can also be cytotoxic under certain conditions (Halliwell and Gutteridge, 1999). In addition, ·O can be easily converted to other ROS that have greater potential for causing cellular damage, such as peroxynitrite (ONOO-) and the extremely reactive hydroxyl (·OH) free radical molecule. Superoxide dismutase (SOD), an antioxidant enzyme present in virtually every cell of the body, plays a crucial role in regulating ·O levels. An imbalance between ·O generation and SOD availability would be expected to have serious consequences for cellular function and survival. We have been exploring the effects of such an imbalance on AHL and NIHL, using mutant mice with a targeted deletion of Sod1, the gene that codes for one copper/zinc isoform of SOD, Cu/Zn SOD, or SOD1. Our experiments with Sod1 knockout mice (129/CD1- Sod1) have provided us with insights into possible chemical pathways underlying NIHL and AHL. Before describing our experiments with Sod1 knockout mice, it may be useful to provide a broad overview of ROS and cellular defenses against them. What are ROS and how are they generated? What do they do, and when are they harmful? How are ROS levels normally regulated in the body?.

Original languageEnglish
Title of host publicationHandbook of Mouse Auditory Research
Subtitle of host publicationFrom Behavior to Molecular Biology
PublisherCRC Press
Number of pages16
ISBN (Electronic)9781420038736
ISBN (Print)0849323282, 9780849323287
StatePublished - Jan 1 2001


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