Immunostaining of oxidized DJ-1 in human and mouse brains.

Immunostaining of oxidized DJ-1 in human and mouse brains.
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在人和小鼠大脑中氧化DJ-1的免疫染色。

DOI:
10.1097/nen.0000000000000087
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发表时间:
2014-07
影响因子:
3.2
通讯作者:
Noguchi N
Noguchi N
中科院分区:
医学4区
文献类型:
--
作者:
Saito Y;Miyasaka T;Hatsuta H;Takahashi-Niki K;Hayashi K;Mita Y;Kusano-Arai O;Iwanari H;Ariga H;Hamakubo T;Yoshida Y;Niki E;Murayama S;Ihara Y;Noguchi N

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文本中提供了补充数字内容。 DJ-1 是帕金森病家族性致病基因的产物,在氧化应激下会优先氧化 Cys106(106 位半胱氨酸残基)。使用针对 Cys106 氧化 DJ-1 (oxDJ-1) 的特异性单克隆抗体,我们检查了 DJ-1 敲除小鼠和野生型小鼠的脑切片以及帕金森病和帕金森病伴痴呆不同路易体阶段病例的人脑切片中的 oxDJ-1 免疫反应性。氧化 DJ-1 免疫反应性在含有神经黑色素的神经元和黑质的神经元突起中显着观察到;路易体还表现出 oxDJ-1 免疫反应性。在纹状体的星形胶质细胞、红核的神经元和神经胶质细胞以及下橄榄核中也检测到了氧化的 DJ-1,所有这些都与运动调节有关。这些观察结果表明,DJ-1 氧化与多个大脑区域(包括黑质的含神经黑色素神经元)的稳态相关,并提出了 oxDJ-1 水平在路易体相关神经退行性疾病进展过程中可能发生变化的可能性。
Supplemental digital content is available in the text. DJ-1, the product of a causative gene of a familial form of Parkinson disease, undergoes preferential oxidation of Cys106 (cysteine residue at position 106) under oxidative stress. Using specific monoclonal antibodies against Cys106 oxidized DJ-1 (oxDJ-1), we examined oxDJ-1 immunoreactivity in brain sections from DJ-1 knockout and wild-type mice and in human brain sections from cases classified into different Lewy body stages of Parkinson disease and Parkinson disease with dementia. Oxidized DJ-1 immunoreactivity was prominently observed in neuromelanin-containing neurons and neuron processes of the substantia nigra; Lewy bodies also showed oxDJ-1 immunoreactivity. Oxidized DJ-1 was also detected in astrocytes in the striatum, in neurons and glia in the red nucleus, and in the inferior olivary nucleus, all of which are related to regulation of movement. These observations suggest the relevance of DJ-1 oxidation to homeostasis in multiple brain regions, including neuromelanin-containing neurons of the substantia nigra, and raise the possibility that oxDJ-1 levels might change during the progression of Lewy body–associated neurodegenerative diseases.