Lev Nirit, Ickowicz Debby, Barhum Yael, Blondheim Netta, Melamed Eldad, Offen Daniel
Laboratory of Neuroscience and department of Neurology, FMRC, Rabin Medical Center, Tel Aviv University, Petah-Tikva, Israel.
Antioxid Redox Signal. 2006 Nov-Dec;8(11-12):1987-95. doi: 10.1089/ars.2006.8.1987.
DJ-1 plays an important role in oxidative stress, and is involved in various neurodegenerative diseases. Accumulating evidence suggests a central role for oxidative stress in multiple sclerosis (MS). The aim of this study was to examine whether changes occur in DJ-1 expression in an animal model of MS, experimental autoimmune encephalomyelitis (EAE). We found upregulation of DJ-1 mRNA and protein expression levels in EAE and a correlation between disease severity and increased DJ-1 levels. Although DJ-1 isoforms were more alkaline in controls, in EAE, a shift was noted toward acidic isoforms. ROS induced by SIN-I exposure led to an increase in DJ-1 mRNA and protein levels in human glioma U-87 cells. Immunocytochemical staining demonstrated that DJ-1 is present both in the cytoplasm and the nuclei of these cells. This is the first report of modulation of DJ-1 expression in EAE. Upregulation of DJ-1 was noted in EAE, and similar results were observed in glioma cells exposed to ROS. In view of the accumulating evidence on the central role of oxidative stress in MS, and the importance of DJ-1 in oxidative stress management by the CNS, we believe that DJ-1 will be found to have a central role in MS.
DJ-1在氧化应激中发挥重要作用,并参与多种神经退行性疾病。越来越多的证据表明氧化应激在多发性硬化症(MS)中起核心作用。本研究的目的是检测在MS的动物模型——实验性自身免疫性脑脊髓炎(EAE)中,DJ-1的表达是否发生变化。我们发现EAE中DJ-1的mRNA和蛋白表达水平上调,且疾病严重程度与DJ-1水平升高之间存在相关性。尽管在对照组中DJ-1同工型更偏碱性,但在EAE中,观察到向酸性同工型的转变。SIN-I暴露诱导的活性氧(ROS)导致人胶质瘤U-87细胞中DJ-1的mRNA和蛋白水平升高。免疫细胞化学染色显示DJ-1存在于这些细胞的细胞质和细胞核中。这是关于EAE中DJ-1表达调节的首次报道。在EAE中观察到DJ-1上调,在暴露于ROS的胶质瘤细胞中也观察到类似结果。鉴于越来越多的证据表明氧化应激在MS中起核心作用,以及DJ-1在中枢神经系统(CNS)氧化应激管理中的重要性,我们认为DJ-1将被发现在MS中起核心作用。