| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2002: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2001: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Research Abstract |
Apoptosis is believed to be a major pathway of cell death in terminally differentiated neurons in many neuropathological conditions. NAIP (neuronal apoptosis inhibitory protein) is a member of intrinsic cellular suppressors of apoptosis (IAPs) and has been identified as a candidate gene involved in the neurodegenerative disease spinal muscular atrophy (SMA). Overexpression of NAIP has been shown to suppress apoptosis in response to various apoptotic inducers. We created full length NAIP transgenic mouse with both TH and CAG promoters. NAIP expression under physiological condition on wild type was trace level by western blot and immunohistochemistry. CAG promoter-NAIP full length transgenic mouse clearly showed NAIP expression in cerebral cortex, hippocampus, nucli in motor cranial nerve, cerebellum, spleen, pancreas, kidney and heart. TH promoter-NAIP full length transgenic mouse showed overexpression of NAIP in substantia Nigra and adrenal medulla. With CAG-promoter NAIP full length mouse, the effect of NAIP against ischemic stress in vivo and cytotoxin, menadion in vitro using primary embryonic fibroblast were evaluated. Overexpressed NAIP in vivo seemed to have adverse effect in terms of ischemic stress. NAIP overexpressed embryonic fibroblast demonstrated cytoprotective effect to menadione treatment. Since NAIP was supposed to be a cell death-determining protein during developmental period, transgenic animals that normally developed presumed to have acquired a compensation against NAIP. On the other hand, primary cells overexpressed NAIP simply showed fundamental NAIP function. NAIP seemed to be a cell death and survive factor based on these results.
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