DJ-1 protects against neurodegeneration caused by focal cerebral ischemia and reperfusion in rats.
Reactive oxygen species (ROS) is massively produced in the brain after cerebral ischemia and reperfusion. It reacts strongly with cellular components, which has detrimental effects and leads to neuronal cell death. DJ-1, which was found to be the causative gene of familial Parkinson's disease PARK7, is a multifunction protein, which plays a key role in transcriptional regulation, and a molecular chaperone. In this study, we investigated the neuroprotective effect of DJ-1 against neurodegeneration caused by ischemia/reperfusion injury. Cerebral ischemia was induced in rats by 120 mins of middle cerebral artery occlusion (MCAO) using an intraluminal introduction method. The intrastriatal injection of recombinant glutathione S-transferase-tagged human DJ-1 (GST-DJ-1) markedly reduced infarct size in 2,3,5-triphenyltetrazolium chloride staining at 3 days after MCAO. In addition, we performed a noninvasive evaluation of ischemic size using magnetic resonance imaging and found a significant reduction of infarct size with the administration of GST-DJ-1. In GST-DJ-1-treated rats, behavioral dysfunction and nitrotyrosine formation were significantly inhibited. Furthermore, GST-DJ-1 markedly inhibited H(2)O(2)-mediated ROS production in SH-SY5Y cells. These results indicate that GST-DJ-1 exerts a neuroprotective effect by reducing ROS-mediated neuronal injury, suggesting that DJ-1 may be a useful therapeutic target for ischemic neurodegeneration.
Yanagisawa
Daijiro
D
Department of Neurobiology, 21st Century COE Program, Kyoto Pharmaceutical University, Kyoto, Japan.
Kitamura
Yoshihisa
Y
Inden
Masatoshi
M
Takata
Kazuyuki
K
Taniguchi
Takashi
T
Morikawa
Shigehiro
S
Morita
Masahito
M
Inubushi
Toshiro
T
Tooyama
Ikuo
I
Taira
Takahiro
T
Iguchi-Ariga
Sanae M M
SM
Akaike
Akinori
A
Ariga
Hiroyoshi
H
D000818:Animals; D001522:Behavior, Animal; D002544:Cerebral Infarction / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D008279:Magnetic Resonance Imaging; D009410:Nerve Degeneration / Q000517:prevention & control*; D015513:Oncogene Proteins / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D000071617:Protein Deglycase DJ-1; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000473:pathology; D014443:Tyrosine / Q000031:analogs & derivatives
D047908:Intracellular Signaling Peptides and Proteins; D015513:Oncogene Proteins; D017382:Reactive Oxygen Species; C002744:3-nitrotyrosine; D014443:Tyrosine; C105131:PARK7 protein, human; D000071617:Protein Deglycase DJ-1