神経細胞および組織におけるUV-DDB蛋白の発現と分布

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Author: 中西, 功夫ほか

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Publication date: 2002-03-25

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Note (General)：: 金沢大学医学部・附属病院アミロイドβ蛋白前駆体(APP)の細胞ドメインと結合する127KDa蛋白,即ちUVdamaged-DNA binding protein(UV-DDB)の脳内分布を明らかにするために本年度は,特異抗体を用いて,非痴呆脳(対照例)2例,アルツハイマー型痴呆脳3例について連続切片...

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Material Type: 文書・図像類
Title: 神経細胞および組織におけるUV-DDB蛋白の発現と分布
Author/Editor: 中西, 功夫
Nakanishi, Isao
Author Heading: 中西, 功夫
Nakanishi, Isao
Publication Date: 2002-03-25
Publication Date (W3CDTF): 2002-03-25
Alternative Title: Expression and distribution of UV-DDB in the nerve cells and tissues
Periodical title: 平成12(2000)年度科学研究費補助金基盤研究(C) 研究成果報告書概要 = 2000 Fiscal Year Final Research Summary
No. or year of volume/issue: 1999 – 2000
Volume: 1999 – 2000
Pages: 2p.-
Text Language Code: jpn
Subject Heading: アルツハイマー病
アミロイド前駆体蛋白
コリンアセチルトランスフェラーゼ
UV-DDB
Alzheimer's disease
Amyloid precursor protein
Choline acetyltransferase
Target Audience: 一般
Note (General): 金沢大学医学部・附属病院
アミロイドβ蛋白前駆体(APP)の細胞ドメインと結合する127KDa蛋白,即ちUVdamaged-DNA binding protein(UV-DDB)の脳内分布を明らかにするために本年度は,特異抗体を用いて,非痴呆脳(対照例)2例,アルツハイマー型痴呆脳3例について連続切片を用いて,βアミロイド蛋白(βA),コリンアセチルトランスフェラーゼ(ChAT),タウ,ユビキチンおよびUV-DDBの免疫組織学的染色を行った.対照例は71才男性,大腸癌と胃癌の二重癌症例と44才男性,腎小細胞癌の症例.また,アルツハイマー病は85才男性,68才男性,84才男性である.共に前頭葉,大脳基底核,海馬のパラホルムアルデヒド固定,パラフィン切片を用いた.各蛋白の発現については正常神経細胞,変性神経細胞,神経原線維変化,老人斑に注目して観察した.ChATの免疫染色性は基底核を除いて著しく低下,特にアルツハイマー病脳の海馬・前頭葉では陰性であった.これに対し,βAおよびユビキチン免疫染色はびまん型,典型的老人斑共にほぼ一致して陽性であり,とくにユビキチンはアルツハイマー病脳の変性神経細胞の領域でタウ陽性神経細胞および細胞突起にも陽性であり,プロテアソーム系の酵素活性の上昇が示唆された.UV-DDB免疫染色は正常対照脳では陰性であったが,アルツハイマー脳では,びまん型老人斑領域や前頭葉,神経原線維変化領域に近い海馬の変性神経細胞核には弱陽性を示した.従って,DNA損傷の際にAPサイトを認識して結合するUV-DDBが特定の変性神経細胞では修復に関与して発現している可能性が考えられた.
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
研究課題/領域番号:11670209, 研究期間(年度):1999 – 2000
出典：「神経細胞および組織におけるUV-DDB蛋白の発現と分布」研究成果報告書　課題番号11670209（KAKEN：科学研究費助成事業データベース（国立情報学研究所））（ https://kaken.nii.ac.jp/ja/grant/KAKENHI-PROJECT-11670209/ ）を加工して作成
DOI: 10.24517/00063982
Access Restrictions: 限定公開
Related Material: https://kaken.nii.ac.jp/ja/search/?kw=00019556
https://kaken.nii.ac.jp/ja/grant/KAKENHI-PROJECT-11670209/
Data Provider (Database): 国立情報学研究所 : 学術機関リポジトリデータベース（IRDB）（機関リポジトリ）
https://irdb.nii.ac.jp
Original Data Provider (Database): 金沢大学 : 金沢大学学術情報リポジトリKURA