UBIQUITIN CARBOXYL-TERMINAL HYDROLASE (PGP 9.5) IS SELECTIVELY PRESENT IN UBIQUITINATED INCLUSION-BODIES CHARACTERISTIC OF HUMAN NEURODEGENERATIVE DISEASES
UBIQUITIN CARBOXYL-TERMINAL HYDROLASE (PGP 9.5) IS SELECTIVELY PRESENT IN UBIQUITINATED INCLUSION-BODIES CHARACTERISTIC OF HUMAN NEURODEGENERATIVE DISEASES
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DOI：
10.1002/path.1711610210
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发表时间：
1990-06-01
影响因子：
7.3
通讯作者：
WILKINSON, KD
中科院分区：
文献类型：
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作者：
LOWE, J;MCDERMOTT, H;WILKINSON, KD
最近发现大脑 PGP 9.5 是一种泛素羧基末端水解酶，这表明应该研究这种蛋白质与几种慢性人类退行性疾病的泛素化细胞内含物特征的关系。福尔马林固定、石蜡处理的切片已知在皮质路易体、神经原纤维缠结、罗森塔尔纤维、皮克小体、运动神经元疾病中的脊髓内含物以及酒精性肝病中的马洛里透明质中含有泛素蛋白缀合物免疫反应性，进行免疫染色以定位 PGP 9.5。弥漫性路易体病中的大多数皮质路易体显示出对 PGP 9.5 的免疫反应性。在阿尔茨海默病中，只有少数松散排列的球状神经原纤维缠结与少数围绕窦状斑块的神经突一起被免疫染色。在小脑星形细胞瘤中，除了一些缺乏明显罗森塔尔纤维的星形胶质细胞中存在强烈的弥漫性细胞质免疫染色外，大多数罗森塔尔纤维的外周也被免疫染色。在皮克氏病中，包涵体没有免疫染色，但肿胀的皮克细胞有强烈的免疫染色。运动神经元疾病中的脊髓内含物没有被染色；然而，与对照病例相比，前角神经元的 PGP 9.5 水平似乎有所增加。没有显示出肝马洛里氏透明质酸的免疫染色，这符合 PGP 9.5 是组织特异性泛素 C 末端水解酶同工酶的建议。神经系统中不同形式的泛素化包涵体中泛素C末端水解酶的差异检测可能构成评估包涵体生物发生阶段的方法的基础，并深入了解包涵体形成的动态。特别是，显示出高水平水解酶的内含物细胞的比例可能将提供退化过程活性水平的标志。
The recent discovery that brain PGP 9.5 is a ubiquitin carboxyl-terminal hydrolase suggests that the role of this protein should be studied in relation to ubiquitinated cellular inclusions characteristic of several chronic human degenerative diseases. Formalin-fixed, paraffin-processed sections known to contain ubiquitin-protein conjugate immunoreactivity in cortical Lewy bodies, neurofibrillary tangles, Rosenthal fibres, Pick bodies, spinal inclusions in motor neurone disease, and Mallory''s hyaline in alcoholic liver disease were immunostained to localize PGP 9.5. The majority of cortical Lewy bodies in diffuse Lewy body disease showed immunoreactivity for PGP 9.5. In Alzheimer''s disease, only a minority of loosely arranged globose-type neurofibrillary tangles were immunostained together with a minority of neurites surrounding sinile plaques. In cerebellar astrocytomas, the periphery of the majority of Rosenthal fibres was immunostained in addition to strong diffuse cytoplasmic immunostaining in some astrocytes lacking apparent Rosenthal fibres. In Pick''s disease, there was no immunostaining of inclusions but there was intense immunostaining of swollen Pick cells. No spinal inclusions in motor neurons disease were stained; however, anterior horn neurons appear to show increased levels of PGP 9.5 compared with those from control cases. No immunostaining of hepatic Mallory''s hyaline was demonstrable, which accords with suggestions that PGP 9.5 is a tissue-specific ubiquitin C-terminal hydrolase isoenzyme. The differential detection of a ubiquitin C-terminal hydrolase in different forms of ubiquitinated inclusion body in the nervous system may form the basis of a method for assessment of the staging of inclusion body biogenesis and give insight into the dynamics of inclusion body formation. In particular, it is possible that the proportion of inclusion-bearing cells showing high levels of the hydrolase will provide a marker of the level of activity of the degenerative process.