Over-expression of X-linked inhibitor of apoptosis protein slows presbycusis in C57BL/6J mice

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• 作者：Jian Wang ; Trevor Menchenton ; Shankai Yin ; Zhiping Yu ; Manohar Bance ; David P. Morris ; Craig S. Moore ; Robert G. Korneluk ; George S. Robertson
• 关键词：X-linked inhibitor of apoptosis protein ; Apoptosis ; Presbycusis ; Mouse
• 刊名：Neurobiology of Aging
• 出版年：2010
• 出版时间：July 2010
• 年：2010
• 卷：31
• 期：7
• 页码：1238-1249
• 全文大小：617 K

文摘

Apoptosis of cochlear cells plays a significant role in age-related hearing loss or presbycusis. In this study, we evaluated whether over-expression of the anti-apoptotic protein known as X-linked Inhibitor of Apoptosis Protein (XIAP) slows the development of presbycusis. We compared the age-related hearing loss between transgenic (TG) mice that over-express human XIAP tagged with 6-Myc (Myc-XIAP) on a pure C57BL/6J genetic background with wild-type (WT) littermates by measuring auditory brainstem responses. The result showed that TG mice developed hearing loss considerably more slowly than WT littermates, primarily within the high-frequency range. The average total hair cell loss was significantly less in TG mice than WT littermates. Although levels of Myc-XIAP in the ear remained constant at 2 and 14 months, there was a marked increase in the amount of endogenous XIAP from 2 to 14 months in the cochlea, but not in the brain, in both genotypes. These results suggest that XIAP over-expression reduces age-related hearing loss and hair cell death in the cochlea.