title: Oxidative stress induction of DJ-1 protein in reactive astrocytes scavenges free radicals and reduces cell injury.
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 (H(2)O(2))-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 H(2)O(2)-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.
authors.affiliation: Department of Neurobiology, Kyoto Pharmaceutical University, Kyoto, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Yanagida
authors.forename: Jun
authors.initials: J
authors.lastname: Tsushima
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Kitamura
authors.forename: Daijiro
authors.initials: D
authors.lastname: Yanagisawa
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Takata
authors.forename: Tomonori
authors.initials: T
authors.lastname: Shibaike
authors.forename: Atsuko
authors.initials: A
authors.lastname: Yamamoto
authors.forename: Takashi
authors.initials: T
authors.lastname: Taniguchi
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Yasui
authors.forename: Takahiro
authors.initials: T
authors.lastname: Taira
authors.forename: Shigehiro
authors.initials: S
authors.lastname: Morikawa
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Inubushi
authors.forename: Ikuo
authors.initials: I
authors.lastname: Tooyama
authors.forename: Hiroyoshi
authors.initials: H
authors.lastname: Ariga
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D002545:Brain Ischemia / Q000378:metabolism / Q000473:pathology; D002460:Cell Line; D004578:Electron Spin Resonance Spectroscopy; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D017665:Hydroxyl Radical / Q000378:metabolism*; D020244:Infarction, Middle Cerebral Artery / Q000378:metabolism / Q000473:pathology; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D018384:Oxidative Stress; D000071617:Protein Deglycase DJ-1; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000494:pharmacology; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D008869:Microtubule-Associated Proteins; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; D017665:Hydroxyl Radical; D006861:Hydrogen Peroxide; C404267:PARK7 protein, rat; D000071617:Protein Deglycase DJ-1