Transgenic mice overexpressing XIAP in neurons show better outcome after transient cerebral ischemia

Trapp, Thorsten; Korhonen, Laura; Besselmann, Michael; Martinez, Rodrigo; Mercer, Eric A.; Lindholm, Dan

doi:10.1016/s1044-7431(03)00013-7

Cited by 81 publications

(76 citation statements)

References 56 publications

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“…XIAP is the most potent and versatile member of the IAP family, 25 and recent studies have demonstrated that overexpression of XIAP in the mouse brain results in neuroprotection in models of focal ischemia in adult animals 43 and HI in P10 mice. 44 A transient increase in XIAP also rendered human carcinoma cells resistant to g-IR.…”

Section: Discussionmentioning

confidence: 99%

“…44 A transient increase in XIAP also rendered human carcinoma cells resistant to g-IR. 45 Using the TG-XIAP mice overexpressing the protein in neurons, 43 we studied the role of caspases in apoptotic, IR-induced injury to neuronal progenitors in the SGZ of the DG. As expected, activation of the initiator caspase-9 and executor caspase-3 was significantly reduced, as judged by the immunoreactivity for the active forms of these proteases at 6 h post-IR.…”

Section: Discussionmentioning

confidence: 99%

“…Seizure-induced, newborn neurons in the DG die, at least partly, through caspase-dependent mechanisms. 51 Increased translocation of AIF may explain why overexpression of XIAP could not rescue the tissue, despite decreased caspase activation and protective effects demonstrated in the same strain of mice in models of adult focal ischemia 43 and neonatal HI. 44 We hypothesize that the cells shift from caspase-dependent to caspase-independent mechanisms of cell death, for example, mediated by AIF.…”

Section: Discussionmentioning

confidence: 99%

“…Transgenic XIAP-overexpressing (TG-XIAP) mice were produced as described. 43 The Thy 1 promoter used to drive the neuronal XIAP expression was active postnatally. WT mice were from the same source as the ones used to produce the TG-XIAP animals (Charles River, Sulzfeld, Germany).…”

Section: Animalsmentioning

confidence: 99%

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Irradiation-induced progenitor cell death in the developing brain is resistant to erythropoietin treatment and caspase inhibition

et al. 2004

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One hemisphere of postnatal day 8 (P8) rats or P10 mice was irradiated with a single dose of 4-12 Gy, and animals were killed from 2 h to 8 weeks after irradiation (IR). In the subventricular zone (SVZ) and the granular cell layer (GCL) of the dentate gyrus, harboring neural and other progenitor cells, nitrosylation and p53 peaked 2-12 h after IR, followed by markers for active caspase-3, apoptosis-inducing factor and TUNEL (6-24 h). Ki67-positive (proliferating) cells had disappeared by 12 h and partly reappeared by 7 days post-IR. The SVZ and GCL areas decreased approximately 50% 7 days after IR. The development of white matter was hampered, resulting in 50-70% less myelin basic protein staining. Pretreatment with erythropoietin did not confer protection against IR. Caspase inhibition by overexpression of XIAP prevented caspase-9 and caspase-3 activation but not cell death, presumably because of increased caspase-independent cell death.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Animalsmentioning

confidence: 99%

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Irradiation-induced progenitor cell death in the developing brain is resistant to erythropoietin treatment and caspase inhibition

et al. 2004

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“…31,32 In the case of in vivo models for stroke and Parkinson's disease, XIAP overexpression not only renders neurons more resistant to cell death but preserves normal function. [33][34][35] The C57BL/6J mouse strain is known for its rapid development of hearing loss with aging. [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.…”

Section: Introductionmentioning

confidence: 99%

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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Pathophysiology of Stroke

Meisel¹,

Prass²,

Wolf³

et al. 2006

Encyclopedia of Molecular Cell Biology and Molecular Medicine

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Transgenic mice overexpressing XIAP in neurons show better outcome after transient cerebral ischemia

Cited by 81 publications

References 56 publications

Irradiation-induced progenitor cell death in the developing brain is resistant to erythropoietin treatment and caspase inhibition

Irradiation-induced progenitor cell death in the developing brain is resistant to erythropoietin treatment and caspase inhibition

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

Pathophysiology of Stroke

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