Expression patterns of retinoblastoma protein in Parkinson disease
Expression patterns of retinoblastoma protein in Parkinson disease
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DOI：
10.1093/jnen/62.1.68
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发表时间：
2003-01-01
影响因子：
3.2
通讯作者：
Achim, CL
中科院分区：
文献类型：
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作者：
Jordan-Sciutto, KL;Dorsey, R;Achim, CL
帕金森病 (PD) 涉及的细胞机制包括氧化应激、炎症反应、过量多巴胺、DNA 损伤和营养支持丧失。已观察到这些刺激可诱导多种细胞类型中细胞周期蛋白的变化。细胞周期进展的关键调节因子之一是视网膜母细胞瘤蛋白 (pRb)；因此，我们评估了 pRb 及其非活性过度磷酸化亚型的染色。 ppRb，来自 PD 患者的尸检组织。在PD中，我们通过免疫组织化学发现黑质、中额叶皮层和海马的神经元细胞质中有丰富的pRb染色。在控制中。 pRb 对黑质神经元的核仁进行弱染色，而在中额叶皮层和海马中未显示出可检测到的染色。 ppRb 染色导致对照病例中神经元的弱细胞质染色转变为 PD 病例中的强核染色，特别是在黑质、中额叶皮层和海马内。在黑质中，ppRb 也与路易体共定位，这是 PD 的病理特征。路易体也存在于弥漫性路易体病 (DLBD) 中，这种疾病的 pRb 或 ppRb 并不一致。这些结果表明，在响应与 PD 相关的神经退行性刺激的神经元中，pRb 及其无活性磷酸亚型发生了变化。
Cellular mechanisms implicated in Parkinson disease (PD) include oxidative stress, inflammatory response, excess dopamine, DNA damage, and loss of trophic support. These stimuli have been observed to induce changes in cell cycle proteins in several cell types. One of the key regulators of cell cycle progression is the retinoblastoma protein (pRb); therefore, we assessed the staining for pRb and its inactive hyperphosphorylated isoform. ppRb, in autopsy tissue from patients with PD. In PD we found abundant pRb staining in neuronal cytoplasm of the substantia nigra, mid-frontal cortex, and hippocampus by immunohistochemistry. In controls. pRb weakly stained nucleoli of neurons in the substantia nigra and exhibited no detectable staining in mid-frontal cortex and hippocampus. Staining for ppRb resulted in a shift from weak cytoplasmic staining in neurons from control cases to strong nuclear staining in PD cases, especially within the substantia nigra, midfrontal cortex, and hippocampus. In the substantia nigra, ppRb also co-localized to Lewy bodies, which are a pathologic feature of PD. Lewy bodies are also found in diffuse Lewy body disease (DLBD) that do not consistently exhibit changes in pRb or ppRb. These results indicate that there are changes in pRb and its inactive phospho-isoform in neurons responding to neurodegenerative stimuli associated with PD.