DJ-1 protects against neurodegeneration caused by focal cerebral ischemia and reperfusion in rats

被引：101

作者：

Yanagisawa, Daijiro ^{[1
]}

Kitamura, Yoshihisa ^{[1
]}

Inden, Masatoshi ^{[1
]}

Takata, Kazuyuki ^{[1
]}

Taniguchi, Takashi ^{[1
]}

Morikawa, Shigehiro ^{[2
]}

Morita, Masahito ^{[2
,3
]}

Inubushi, Toshiro ^{[2
]}

Tooyama, Ikuo ^{[4
]}

Taira, Takahiro ^{[5
]}

Iguchi-Ariga, Sanae M. M. ^{[6
]}

Akaike, Akinori ^{[7
]}

Ariga, Hiroyoshi ^{[8
]}

机构：

[1] Kyoto Pharmaceut Univ, 21st Century COE Program, Dept Neurobiol, Yamashina Ku, Kyoto 6078414, Japan

[2] Shiga Univ Med Sci, Biomed MR Sci Res Ctr, Otsu, Shiga 52021, Japan

[3] Japan Sci & Technol Agcy, PRESTO, Kawaguchi, Saitama, Japan

[4] Shiga Univ Med Sci, Mol Neurosci Res Ctr, Otsu, Shiga 52021, Japan

[5] Univ Yamanashi, Interdisciplinary Grad Sch Med & Engn, Dept Mol Cell Biol, Chuo, Japan

[6] Hokkaido Univ, Grad Sch Agr, Sapporo, Hokkaido, Japan

[7] Kyoto Univ, Grad Sch Pharmaceut Sci, Dept Pharmacol, Kyoto, Japan

[8] Hokkaido Univ, Grad Sch Pharmaceut Sci, Dept Mol Biol, Sapporo, Hokkaido, Japan

来源：

JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM | 2008年 / 28卷 / 03期

关键词：

DJ-1; focal cerebral ischemia; ischemia/reperfusion injury; neuroprotection; reactive oxygen species; ARTERY OCCLUSION; CRYSTAL-STRUCTURE; BRAIN-INJURY; IN-VIVO; ANTIOXIDATIVE STRESS; ANDROGEN RECEPTOR; S-NITROSYLATION; FUSION PROTEIN; TRANSDUCTION; MODEL;

D O I：

10.1038/sj.jcbfm.9600553

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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 H2O2-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.

引用

页码：563 / 578

页数：16

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