1. Oxidative Stress Induction of DJ-1 Protein in Reactive Astrocytes Scavenges Free Radicals and Reduces Cell Injury
- Author
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Takahiro Taira, Atsuko Yamamoto, Yoshihisa Kitamura, Kazuyuki Takata, Hiroyoshi Ariga, Shigehiro Morikawa, Takashi Taniguchi, Takashi Yanagida, Jun Tsushima, Ikuo Tooyama, Toshihiro Inubushi, Hiroyuki Yasui, Tomonori Shibaike, and Daijiro Yanagisawa
- Subjects
DJ-1 ,Aging ,Recombinant Fusion Proteins/pharmacology ,Protein Deglycase DJ-1 ,medicine.disease_cause ,release ,Biochemistry ,Brain Ischemia ,chemistry.chemical_compound ,Cell Line ,Chemistry ,lcsh:Cytology ,Rats ,Infarction, Middle Cerebral Artery ,General Medicine ,Astrocytes/metabolism ,Research Papers ,Recombinant Proteins ,Brain Ischemia/metabolism ,Cell biology ,neuroprotection ,Electron Spin Resonance Spectroscopy ,Hydroxyl Radical/metabolism ,medicine.symptom ,Microtubule-Associated Proteins ,Infarction, Middle Cerebral Artery/metabolism ,Programmed cell death ,Oxidative Stress ,Infarction, Middle Cerebral Artery/pathology ,Recombinant Fusion Proteins ,Humans ,Recombinant Proteins/genetics ,Ischemia ,Oxidative phosphorylation ,Neuroprotection ,Lesion ,medicine ,Animals ,Hydrogen Peroxide/pharmacology ,lcsh:QH573-671 ,Microtubule-Associated Proteins/genetics ,oxidative stress sensor ,Hydroxyl Radical ,Brain Ischemia/pathology ,Microtubule-Associated Proteins/metabolism ,astrocytes ,Hydrogen Peroxide ,Cell Biology ,Glutathione ,medicine.disease ,In vitro ,focal ischemia ,Recombinant Proteins/metabolism ,Oxidative stress - Abstract
Astrocytes, one of the predominant types of glial cells, function as both supportive and metabolic cells for the brain. Under cerebral ischemia/reperfusion-induced oxidative conditions, astrocytes accumulate and activate in the ischemic region. DJ-1 has recently been shown to be a sensor of oxidative stress in living cells. However, the function of astrocytic DJ-1 is still unknown. In the present study, to clarify the effect of astrocytic DJ-1 protein under massive oxidative insult, we used a focal ischemic rat model that had been subjected to middle cerebral artery occlusion (MCAO) and reperfusion. We then investigated changes in the distribution of DJ-1 in astrocytes, DJ-1 release from cultured astrocytes, and the effects of recombinant DJ-1 protein on hydrogen peroxide (H2O2)-induced death in normal and DJ-1-knockdown SH-SY5Y cells and on in vitro scavenging of hydroxyl radicals (•OH) by electron spin resonance spectrometry. At 24 h after 2-h MCAO and reperfusion, an infarct lesion was markedly observed using magnetic resonance imaging and 2,3,5-triphenyltetrazolium chloride staining. In addition, reactive astrocytes enhanced DJ-1 expression in the penumbral zone of the ischemic core and that DJ-1 protein was extracellularly released from astrocytes by H2O2 in in vitro primary cultures. Although DJ-1-knockdown SH-SY5Y cells were markedly vulnerable to oxidative stress, treatment with glutathione S-transferase-tagged recombinant human DJ-1 protein (GST-DJ-1) significantly inhibited H2O2-induced cell death. In addition, GST-DJ-1 protein directly scavenged•OH. These results suggest that oxidative stress induces the release of astrocytic DJ-1 protein, which may contribute to astrocyte-mediated neuroprotection.
- Published
- 2009