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Oxidative stress induction of DJ-1 protein in reactive astrocytes scavenges free radicals and reduces cell injury.
Title: | Oxidative stress induction of DJ-1 protein in reactive astrocytes scavenges free radicals and reduces cell injury. |
Authors: | Yanagida, Takashi Browse this author | Tsushima, Jun Browse this author | Kitamura, Yoshihisa Browse this author →KAKEN DB | Yanagisawa, Daijiro Browse this author | Takata, Kazuyuki Browse this author →KAKEN DB | Shibaike, Tomonori Browse this author | Yamamoto, Atsuko Browse this author | Taniguchi, Takashi Browse this author →KAKEN DB | Yasui, Hiroyuki Browse this author →KAKEN DB | Taira, Takahiro Browse this author →KAKEN DB | Morikawa, Shigehiro Browse this author →KAKEN DB | Inubushi, Toshihiro Browse this author | Tooyama, Ikuo Browse this author →KAKEN DB | Ariga, Hiroyoshi Browse this author →KAKEN DB |
Keywords: | DJ-1 | release | astrocytes | focal ischemia | oxidative stress sensor | neuroprotection |
Issue Date: | Jan-2009 |
Publisher: | Hindawi Pub. |
Journal Title: | Oxidative medicine and cellular longevity |
Volume: | 2 |
Issue: | 1 |
Start Page: | 36 |
End Page: | 42 |
Publisher DOI: | 10.4161/oxim.2.1.7985 |
PMID: | 20046643 |
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. |
Type: | article |
URI: | http://hdl.handle.net/2115/53702 |
Appears in Collections: | 薬学研究院 (Faculty of Pharmaceutical Sciences) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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Submitter: 有賀 寛芳
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