Experimental encephalomyelitis induces changes in DJ-1: implications for oxidative stress in multiple sclerosis.
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.
Lev
Nirit
N
Laboratory of Neuroscience and department of Neurology, FMRC, Rabin Medical Center, Tel Aviv University, Petah-Tikva, Israel. lev.nirit@gmail.com
Ickowicz
Debby
D
Barhum
Yael
Y
Blondheim
Netta
N
Melamed
Eldad
E
Offen
Daniel
D
D000818:Animals; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008809:Mice, Inbred C3H; D009025:Morpholines / Q000737:chemistry / Q000494:pharmacology; D009103:Multiple Sclerosis / Q000378:metabolism*; D015513:Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D018384:Oxidative Stress; D054464:Peroxiredoxins; D000071617:Protein Deglycase DJ-1; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D013558:Sydnones / Q000737:chemistry / Q000494:pharmacology; D015854:Up-Regulation
D047908:Intracellular Signaling Peptides and Proteins; D009025:Morpholines; D015513:Oncogene Proteins; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D013558:Sydnones; D054464:Peroxiredoxins; C105131:PARK7 protein, human; C503466:PARK7 protein, mouse; D000071617:Protein Deglycase DJ-1