Oxidative stress induction of DJ-1 protein in reactive astrocytes scavenges free radicals and reduces cell injury.
Oxidative stress induction of DJ-1 protein in reactive astrocytes scavenges free radicals and reduces cell injury.
复制标题
DOI：
10.4161/oxim.2.1.7985
复制
发表时间：
2009-01
影响因子：
--
通讯作者：
Ariga H
中科院分区：
文献类型：
--
作者：
Yanagida T;Tsushima J;Kitamura Y;Yanagisawa D;Takata K;Shibaike T;Yamamoto A;Taniguchi T;Yasui H;Taira T;Morikawa S;Inubushi T;Tooyama I;Ariga H
星形胶质细胞是神经胶质细胞的主要类型之一，对大脑起支持和代谢细胞的作用。在脑缺血/再灌注诱导的氧化条件下，星形胶质细胞在缺血区域积聚并活化。DJ-1最近被证明是活细胞中氧化应激的传感器。然而，星形胶质细胞DJ-1的功能仍然是未知的。在本研究中，为了阐明星形胶质细胞DJ-1蛋白在大规模氧化损伤下的作用，我们使用了一个局灶性缺血大鼠模型，该模型已进行大脑中动脉闭塞（MCAO）和再灌注。然后，我们研究了DJ-1在星形胶质细胞中分布的变化，DJ-1从培养的星形胶质细胞中的释放，以及重组DJ-1蛋白对正常和DJ-1敲低的SH-SY 5 Y细胞中过氧化氢（H2 O2）诱导的死亡的影响，以及通过电子自旋共振光谱法体外清除羟基自由基（·OH）。在24小时后2小时MCAO和再灌注，梗死病变明显观察到磁共振成像和2，3，5-三苯基氯化四氮唑染色。此外，反应性星形胶质细胞增强DJ-1的表达在缺血中心的半影区和DJ-1蛋白在体外原代培养物中由H2 O2从星形胶质细胞中细胞外释放。虽然DJ-1敲低SH-SY 5 Y细胞明显易受氧化应激的影响，但谷胱甘肽S-转移酶标记的重组人DJ-1蛋白（GST-DJ-1）治疗可显著抑制H2 O2诱导的细胞死亡。此外，GST-DJ-1蛋白还能直接清除·OH。这些结果表明，氧化应激诱导星形胶质细胞DJ-1蛋白的释放，这可能有助于星形胶质细胞介导的神经保护。
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.
登录
查看更多内容
影响因子：
2.5
作者：
Maita, Chinatsu;Tsuji, Sachiko;Ariga, Hiroyoshi
通讯作者：
Ariga, Hiroyoshi
影响因子：
4.8
作者：
Honbou, K;Suzuki, NN;Inagaki, F
通讯作者：
Inagaki, F
影响因子：
56.9
作者：
Bonifati, V;Rizzu, P;Heutink, P
通讯作者：
Heutink, P
DOI：
10.1073/pnas.0607260103
发表时间：
2006-10-10
影响因子：
11.1
作者：
Clements, Casey M.;McNally, Richard S.;Ting, Jenny P-Y.
通讯作者：
Ting, Jenny P-Y.
影响因子：
7.7
作者：
Taira, T;Saito, Y;Ariga, H
通讯作者：
Ariga, H