Expression and distribution of UV-DDB in the nerve cells and tissues

紫外线损伤DNA结合蛋白(UV-DdB)是由127kDa和48kDa组成的异源二聚体组成的胞质内蛋白，前者与淀粉样蛋白前体(AmyloidβProducer，APP)的胞质结构域结合。在本研究项目中，我们用免疫组织化学方法(Watanabe T.at al.，J.NeuroChemem)研究了UV-DDB在正常和病变脑(3例阿尔茨海默病，2例非痴呆症尸检病例)中的表达和分布。72、2549-556、1999)。多聚甲醛固定的石蜡切片上还应用了抗β-淀粉样蛋白(βA)、胆碱乙酰转移酶(ChAT)、tau、泛素的特异性抗体。在正常神经细胞、变性神经细胞、神经原纤维缠结以及额叶、大脑基底核和下丘脑的衰老斑块上均有表达。阿尔茨海默病患者脑内ChAT免疫组织化学染色均为阴性。βA和泛素免疫反应在老年斑中呈阳性。尤其是变性的神经细胞及其突起呈泛素免疫反应，提示蛋白体酶活性增强。UV-DDB免疫反应在对照组为阴性，而阿尔茨海默病患者脑内退行性神经细胞UV-DDB弱阳性，尤其是额叶和下丘脑的弥漫型老年斑和神经原纤维缠结区域。因此，在DNA损伤过程中与蛋白质AP位点结合的UV-DDB可能在特定变性神经细胞的细胞核中表达，用于修复过程

UV-damaged-DNA binding protein (UV-DDB) is an intracytoplasmic protein of heterodimer consisting of 127 kDa and 48 kDa, the former of which binds with the cytoplasmic domain of amyloid β protein precursor (APP). In this research project, we immunohistochemically investigated the expression and distribution of UV-DDB in the normal and diseased brains (3 Alzheimer's disease cases, 2 non-dementia autopsy cases) by using the specific polyclonal antibodies (Watanabe T.at al., J.Neurochem. 72, 2, 549-556, 1999). Specific antibodies against β-amyloid protein (βA), choline acetyltransferatse (ChAT), tau, ubiquitin were also applied on the paraformaldehyde-fixed paraffin section of those cases. Expression of each protein was noted on normal nerve cells, degenerating nerve cells, neurofibrillary tangles, and senile plaques in the frontal lobes, cerebral basilar nuclei and hypocampus. ChAT immunohistochemistry was negative in Alzheimer's deisease brain. βA and ubiquitin immunoreactivities were positive in the senile plaques. Particularly the degenerating nerve cells and their processes were immunoreactive with ubiquitin, suggesting the increase of proteosome enzymatic actibity. UV-DDB immunoreactivity was negative in the control brains, but Alzheimer's diseased brains were weakly positive for UV-DDB in degenerating nerve cells, particularly in areas of the diffuse type senile plaques and neurofibrillary tangles in the frontal lobes and hypocampus. Thus, UV-DDB which binds to AP sites of the protein during DNA damage may be expressed in the nuclei of particular degenerating nerve cells for reparative processes