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

UV-DDB在神经细胞和组织中的表达和分布

• 批准号: 11670209
• 负责人: NAKANISHI Isao
• 金额: $ 2.11万
• 依托单位: Kanazawa University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11670209/
• 关键词: Alzheimer's disease; Amyloid precursor protein; Choline acetyltransferase; UV-DDB

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

紫外线损伤DNA结合蛋白（UV-damaged-DNA binding protein，UV-DDB）是由127 kDa和48 kDa分子组成的异源二聚体，其中127 kDa分子与淀粉样β蛋白前体（amyloid β protein precursor，APP）的胞浆区结合。在该研究项目中，我们通过使用特异性多克隆抗体（Watanabe www.example.com al.，J.Neurochem. 72，2，549 - 556，1999）。同时应用β-淀粉样蛋白（β A）、胆碱乙酰转移酶（ChAT）、tau蛋白、泛素等特异性抗体对石蜡切片进行检测。在额叶、大脑基底核和海马下区的正常神经细胞、变性神经细胞、神经纤维缠结和老年斑上均观察到每种蛋白的表达。Alzheimer病脑组织ChAT免疫组化染色阴性。β A和泛素免疫反应阳性。特别是变性神经细胞及其突起呈泛素免疫反应阳性，提示蛋白体酶活性增强。UV-DDB免疫反应是阴性的，在对照组的大脑，但阿尔茨海默氏病的大脑呈弱阳性的UV-DDB在退化的神经细胞，特别是在弥漫型老年斑和神经纤维缠结在额叶和海马区。因此，在DNA损伤期间结合蛋白质的AP位点的UV-DDB可在特定退化神经细胞的核中表达用于修复过程

项目成果

Isohara T, et al : "Phosphorylation of the cytoplasmic domain of Alzheimer's β-amyloid precursor protein at Ser 655 by a novel protein kinase."Biochem.Biophys.Res.Comm.. 258・2. 300-305 (1999)

Isohara T 等人：“通过新型蛋白激酶对阿尔茨海默病 β-淀粉样前体蛋白的胞质结构域在 Ser 655 进行磷酸化。”Biochem.Biophys.Res.Comm. 258·2 (1999)。

Muroishi,Y. et al : "Immunohistochemical and in situ hybridization studies neurons of choline acetyltransferase in large motor neurons of the human spinal cord."Histol.Histopathol.. 15・3. 689-696 (2000)

Muroishi, Y. 等人：“免疫组织化学和原位杂交研究人类脊髓大运动神经元中的胆碱乙酰转移酶神经元。” 15・3 (2000)。

Isohara T, et al.: "Phosphorylation of the cytoplasmic domain of Alzheimer's β-amyloid precursor protein at Ser 655 by a novel protein kinase."Biochem.Biophys.Res.Comm.. 258(2). 300-305 (1999)

Isohara T 等人：“通过新型蛋白激酶对阿尔茨海默病 β-淀粉样前体蛋白的胞质结构域在 Ser 655 处进行磷酸化。”Biochem.Biophys.Res.Comm. 258(2) (1999)。

Oda,Y.: "Choline acetyltransferase : the structure, distribution and pathologic changes in the central nervous system."Pathol.Int.. 49・11. 921-937 (1999)

Oda, Y.：“胆碱乙酰转移酶：中枢神经系统的结构、分布和病理变化。Pathol.Int.. 921-937 (1999)”

Youko Muroishi, Satomi Kasashima, Isao Nakanishi and Yoshio Oda: "Immunohistochemical and in situ hybridization studies of choline acetyltransferase in large motor neurons of the human spinal cord."Histol.Histopathol.. 15(3). 689-696 (2000)

Youko Muroishi、Satomi Kasashima、Isao Nakanishi 和 Yoshio Oda：“人类脊髓大运动神经元中胆碱乙酰转移酶的免疫组织化学和原位杂交研究。”Histol.Histopathol.. 15(3)。