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

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

doi:10.1016/j.neurobiolaging.2008.07.016

Cited by 39 publications

(40 citation statements)

References 72 publications

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“…In addition to the protective effect of XIAP overexpression against acoustic overstimulation, it is also possible that the inner ears of TG mice were healthier before the acoustic trauma because TG mice showed a delayed development of presbycusis, as reported in our previous study. 40 However, this potential confounding factor can largely be ruled out because the control recordings of ABR do not show any difference in hearing status across groups (Table 1) and there is no difference in HC counts in TG mice and WT mice at this age when the cochleogram normative values were established in our lab (data not reported).…”

Section: Discussionmentioning

confidence: 93%

“…71 Briefly, a linearized plasmid construct consisting of the Ubiquitin C promoter, six repeats of the 9E10 myc epitope tag fused to the amino terminus of the human XIAP coding region, and a polyadenylation signal from stria vascularis-40 was microinjected into the male pronucleus of C57BL/6J X C3 H F1 zygotes. C57BL/6J X C3 H F1 offsprings were backcrossed over 15 generations against the WT C57BL/6J mice to obtain ub-XIAP TG animals on a pure C57BL/6J genetic background.…”

Section: Subjects and Experiments Overviewmentioning

confidence: 99%

“…[36][37][38][39] Using C57BL/6J mice that overexpress human XIAP under control of the ubiquitin promoter (ubXIAP), we have found that in comparison with wild-type (WT) littermates, ubXIAP mice showed a delay in the development of presbycusis, which was also associated with a reduction in cochlear HC loss. 40 In this study, we have used these transgenic (TG) mice to determine the effects of XIAP overexpression on NIHL and associated cochlear damage. Figure 1 shows the ABR threshold shifts 1 and 4 weeks after exposure to acoustic overstimulation of 125 dB sound pressure level (SPL) for 6 h. Although the acoustic overstimulation occurred at two frequencies (1 and 6 kHz), the threshold shifts appeared to be greater at middle to high frequencies (4 kHz and above) than at the lower frequency (2 kHz).…”

Section: Introductionmentioning

confidence: 99%

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Overexpression of X-linked inhibitor of apoptosis protein protects against noise-induced hearing loss in mice

et al. 2011

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Apoptosis is responsible for cochlear cell death induced by noise. Here, we show that transgenic (TG) mice that overexpress X-linked inhibitor of apoptosis protein (XIAP) under control of the ubiquitin promoter display reduced hearing loss and cochlear damage induced by acoustic overstimulation (125 dB sound pressure level, 6 h) compared with wild-type (WT) littermates. Hearing status was evaluated using the auditory brainstem response (ABR), whereas cochlear damage was assessed by counts of surviving hair cells (HCs) and spiral ganglion neurons (SGNs) as well as their fibers to HCs. Significantly smaller threshold shifts were found for TG mice than WT littermates. Correspondingly, the TG mice also showed a reduced loss of HCs, SGNs and their fibers to HCs. HC loss was limited to the basal end of the cochlea that detects high frequency sound. In contrast, the ABRs demonstrated a loss of hearing sensitivity across the entire frequency range tested (2-32 kHz) indicating that the hearing loss could not be fully attributed to HC loss alone. The TG mice displayed superior hearing sensitivity over this whole range, suggesting that XIAP overexpression reduces noise-induced hearing loss not only by protecting HCs but also other components of the cochlea.

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Section: Discussionmentioning

confidence: 93%

Section: Subjects and Experiments Overviewmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Overexpression of X-linked inhibitor of apoptosis protein protects against noise-induced hearing loss in mice

et al. 2011

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“…For example, T-cell-specific overexpression of XIAP resulted in the accumulation of thymocytes and/or T cells in primary and secondary lymphoid tissue and resistance to antiFas-and/or dexamethasone-induced apoptosis (41); and neuronal overexpression of XIAP promoted resistance to brain injury caused by transient forebrain ischemia after occlusion of the middle cerebral artery (42), protecting the neonatal brain against hypoxia ischemia (43). Overexpression of XIAP in nigrostriatal dopaminergic neurons promoted resistance to the damaging effects of the dopaminergic neurotoxin MPTP (44); and overexpression of XIAP slowed age-related hearing loss in C57BL/6J mice (45).…”

Section: Clinical-translational Advancesmentioning

confidence: 99%

X-linked Inhibitor of Apoptosis: A Chemoresistance Factor or a Hollow Promise

Kashkar

2010

Clinical Cancer Research

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The X-linked inhibitor of apoptosis (XIAP) is the only cellular protein that has evolved to potently inhibit the enzymatic activity of mammalian caspases and promotes resistance to apoptosis. Given its role in apoptosis and its frequently elevated expression in malignant cells, XIAP has garnered the most attention as a promising therapeutic target in cancer to overcome drug resistance. Accordingly, XIAP is thought to render tumor cells resistant to chemotherapy through its ability to inhibit caspases, and it is on this basis that XIAP has been proposed as an important adverse biomarker for chemoresistance in cancer patients. Here, the current understanding of the role of XIAP in cancer is reviewed. Further, the notion is explored that the elevated XIAP expression frequently observed in malignant tissues is, at least, not exclusively responsible for the resistance of tumor cells to conventional therapeutic treatment; rather, the function of XIAP seems to be conducive to the process of malignant transformation and/or progression.

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“…It is an extremely potent suppressor of apoptosis and selectively binds and inhibits caspase-3, caspase-7, and caspase-9 (Deveraux et al, 1997). It was discovered that XIAP inhibited apoptosis of cochlear cells under various conditions such as age-related hearing loss and cisplatin-induced deafness (Cooper et al, 2006;Wang et al, 2008). Studies demonstrated that the severity of hearing loss induced by cisplatin was significantly reduced by XIAP (Cooper et al, 2006).…”

Section: Therapeutic Genes For Inner Ear Gene Therapymentioning

confidence: 99%

Current Status and Prospects of Gene Therapy for the Inner Ear

2011

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Inner ear diseases are common and often result in hearing disability. Sensorineural hearing loss is the main cause of hearing disability. So far, no effective treatment is available although some patients may benefit from a hearing aid equipped with a hearing amplifier or from cochlear implantation. Inner ear gene therapy has become an emerging field of study for the treatment of hearing disability. Numerous new discoveries and tremendous advances have been made in inner ear gene therapy including gene vectors, routes of administration, and therapeutic genes and targets. Gene therapy may become a treatment option for inner ear diseases in the near future. In this review, we summarize the current state of inner ear gene therapy including gene vectors, delivery routes, and therapeutic genes and targets by examining and analyzing publications on inner ear gene therapy from the literature and patent documents, and identify promising patents, novel techniques, and vital research projects. We also discuss the progress and prospects of inner ear gene therapy, the advances and shortcomings, with possible solutions in this field of research.

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

Cited by 39 publications

References 72 publications

Overexpression of X-linked inhibitor of apoptosis protein protects against noise-induced hearing loss in mice

Overexpression of X-linked inhibitor of apoptosis protein protects against noise-induced hearing loss in mice

X-linked Inhibitor of Apoptosis: A Chemoresistance Factor or a Hollow Promise

Current Status and Prospects of Gene Therapy for the Inner Ear

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