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著者: Shinichi Someya, Jinze Xu, Kenji Kondo, Dalian Ding, Richard J Salvi, Tatsuya Yamasoba, Peter S Rabinovitch, Richard Weindruch, Christiaan Leeuwenburgh, Masaru Tanokura, Tomas A Prolla
雑誌名: Proc Natl Acad Sci U S A. 2009 Nov 17;106(46):19432-7. doi: 10.1073/pnas.0908786106. Epub 2009 Nov 9.
Abstract/Text
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.
PMID 19901338 Proc Natl Acad Sci U S A. 2009 Nov 17;106(46):19432-7. doi: 10.1073/pnas.0908786106. Epub 2009 Nov 9.
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