Oxidative stress induction of DJ-1 protein in reactive astrocytes scavenges free radicals and reduces cell injury.
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.
Yanagida
Takashi
T
Department of Neurobiology, Kyoto Pharmaceutical University, Kyoto, Japan.
Tsushima
Jun
J
Kitamura
Yoshihisa
Y
Yanagisawa
Daijiro
D
Takata
Kazuyuki
K
Shibaike
Tomonori
T
Yamamoto
Atsuko
A
Taniguchi
Takashi
T
Yasui
Hiroyuki
H
Taira
Takahiro
T
Morikawa
Shigehiro
S
Inubushi
Toshihiro
T
Tooyama
Ikuo
I
Ariga
Hiroyoshi
H
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
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