Astroglial NF-κB mediates oxidative stress by regulation of NADPH oxidase in a model of retinal ischemia reperfusion injury.
Astroglial NF-κB mediates oxidative stress by regulation of NADPH oxidase in a model of retinal ischemia reperfusion injury.
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DOI：
10.1111/j.1471-4159.2011.07595.x
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发表时间：
2012-02
影响因子：
4.7
通讯作者：
Shestopalov VI
中科院分区：
文献类型：
--
作者：
Barakat DJ;Dvoriantchikova G;Ivanov D;Shestopalov VI
Astrocytes undergo rapid activation after injury, which is mediated in part by the transcription factor NF-κB. Consequently, activated astrocytes have been shown to induce the NF-κB regulated phagocyte NADPH oxidase (PHOX), resulting in elevated production of reactive oxygen species (ROS). We investigated the regulatory mechanisms of PHOX-induced oxidative stress in astrocytes and its non cell-autonomous effects on retinal ganglion cell (RGC) loss following retinal ischemia-reperfusion (IR) injury. To study PHOX activity and neurotoxicity mediated by glial NF-κB, we employed GFAP-IκBα-dn transgenic mice (TG), where the NF-κB canonical pathway is suppressed specifically in astrocytes. Our analysis showed that NF-κB activation in astrocytes correlated with an increased expression of PHOX and ROS production in primary cells and whole retinas subjected to oxygen-glucose deprivation (OGD) or IR injury. Selective blockade of NF-κB in astrocytes or application of NADPH oxidase inhibitors suppressed RGC loss in co-cultures with astroglia challenged by OGD. Furthermore, genetic suppression of astroglial NF-κB reduced oxidative stress in ganglion layer neurons in vivo in retinal IR. Collectively, our results suggest that astroglial NF-κB-regulated PHOX activity is a crucial toxicity pathway in the pathogenesis of retinal IR injury.
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DOI：
10.1083/jcb.85.3.890
发表时间：
1980-06
期刊：
The Journal of cell biology
影响因子：
--
作者：
McCarthy KD;de Vellis J
通讯作者：
de Vellis J
影响因子：
15.3
作者：
Brambilla, R;Bracchi-Ricard, V;Hu, WH;Frydel, B;Bramwell, A;Karmally, S;Green, EJ;Bethea, JR
通讯作者：
Bethea, JR
影响因子：
6.3
作者：
Park, Laibaik;Anrather, Josef;Iadecola, Costantino
通讯作者：
Iadecola, Costantino
影响因子：
4.8
作者：
Anrather, J;Racchumi, G;Iadecola, C
通讯作者：
Iadecola, C
影响因子：
4.4
作者：
Moore, Samantha F.;MacKenzie, Amanda B.
通讯作者：
MacKenzie, Amanda B.