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

Jian Wang; Trevor Menchenton; Shankai Yin; Zhiping Yu; Manohar Bance; David P. Morris; Craig S. Moore; Robert G. Korneluk; George S. Robertson

doi:10.1016/j.neurobiolaging.2008.07.016

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

Jian Wang, Trevor Menchenton, Shankai Yin, Zhiping Yu, Manohar Bance, David P. Morris, Craig S. Moore, Robert G. Korneluk, George S. Robertson

Medicine

Research output: Contribution to journal › Article › peer-review

33 Citations (Scopus)

Abstract

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.

Original language	English
Pages (from-to)	1238-1249
Number of pages	12
Journal	Neurobiology of Aging
Volume	31
Issue number	7
DOIs	https://doi.org/10.1016/j.neurobiolaging.2008.07.016
Publication status	Published - Jul 2010

Bibliographical note

Funding Information:
This study is supported by grant of Canadian Institute of Health Research (MOP-79452) and the grant of National Nature Science Foundation of China (30672294/C030310). We thank Dr. Peter Liston, who had generated the ubXIAP transgenic mice and generously provided this valuable resource for our study.

ASJC Scopus Subject Areas

General Neuroscience
Ageing
Developmental Biology
Clinical Neurology
Geriatrics and Gerontology

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10.1016/j.neurobiolaging.2008.07.016

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

abstract = "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.",

author = "Jian Wang and Trevor Menchenton and Shankai Yin and Zhiping Yu and Manohar Bance and Morris, {David P.} and Moore, {Craig S.} and Korneluk, {Robert G.} and Robertson, {George S.}",

note = "Funding Information: This study is supported by grant of Canadian Institute of Health Research (MOP-79452) and the grant of National Nature Science Foundation of China (30672294/C030310). We thank Dr. Peter Liston, who had generated the ubXIAP transgenic mice and generously provided this valuable resource for our study.",

year = "2010",

month = jul,

doi = "10.1016/j.neurobiolaging.2008.07.016",

language = "English",

volume = "31",

pages = "1238--1249",

journal = "Neurobiology of Aging",

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T1 - Over-expression of X-linked inhibitor of apoptosis protein slows presbycusis in C57BL/6J mice

AU - Wang, Jian

AU - Menchenton, Trevor

AU - Yin, Shankai

AU - Yu, Zhiping

AU - Bance, Manohar

AU - Morris, David P.

AU - Moore, Craig S.

AU - Korneluk, Robert G.

AU - Robertson, George S.

N1 - Funding Information: This study is supported by grant of Canadian Institute of Health Research (MOP-79452) and the grant of National Nature Science Foundation of China (30672294/C030310). We thank Dr. Peter Liston, who had generated the ubXIAP transgenic mice and generously provided this valuable resource for our study.

PY - 2010/7

Y1 - 2010/7

N2 - 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.

AB - 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.

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

Abstract

Bibliographical note

ASJC Scopus Subject Areas

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