期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 106, 期 46, 页码 19432-19437出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0908786106
关键词
aging; antioxidant; cochlea; oxidative stress; presbycusis
资金
- National Institutes of Health [AG021905, AG189222, AG17994, AG21042]
- Ministry of Education, Culture, Sports, Science, and Technologies of Japan
- Marine Bio Foundation
Age-related hearing loss (AHL), known as presbycusis, is a universal feature of mammalian aging and is the most common sensory disorder in the elderly population. The molecular mechanisms underlying AHL are unknown, and currently there is no treatment for the disorder. Here we report that C57BL/6J mice with a deletion of the mitochondrial pro-apoptotic gene Bak exhibit reduced age-related apoptotic cell death of spiral ganglion neurons and hair cells in the cochlea, and prevention of AHL. Oxidative stress induces Bak expression in primary cochlear cells, and Bak deficiency prevents apoptotic cell death. Furthermore, a mitochondrially targeted catalase transgene suppresses Bak expression in the cochlea, reduces cochlear cell death, and prevents AHL. Oral supplementation with the mitochondrial antioxidants alpha-lipoic acid and coenzyme Q(10) also suppresses Bak expression in the cochlea, reduces cochlear cell death, and prevents AHL. Thus, induction of a Bak-dependent mitochondrial apoptosis program in response to oxidative stress is a key mechanism of AHL in C57BL/6J mice.
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