Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
5846501 | Toxicology and Applied Pharmacology | 2013 | 8 Pages |
Abstract
Stroke is a complex disease that may involve oxidative stress-related pathways in its pathogenesis. The nuclear factor erythroid-2-related factor 2/antioxidant response element (Nrf2/ARE) pathway plays an important role in inducing phase II detoxifying enzymes and antioxidant proteins and thus has been considered a potential target for neuroprotection in stroke. The aim of the present study was to determine whether eriodictyol-7-O-glucoside (E7G), a novel Nrf2 activator, can protect against cerebral ischemic injury and to understand the role of the Nrf2/ARE pathway in neuroprotection. In primary cultured astrocytes, E7G increased the nuclear localization of Nrf2 and induced the expression of the Nrf2/ARE-dependent genes. Exposure of astrocytes to E7G provided protection against oxygen and glucose deprivation (OGD)-induced oxidative insult. The protective effect of E7G was abolished by RNA interference-mediated knockdown of Nrf2 expression. In vivo administration of E7G in a rat model of focal cerebral ischemia significantly reduced the amount of brain damage and ameliorated neurological deficits. These data demonstrate that activation of Nrf2/ARE signaling by E7G is directly associated with its neuroprotection against oxidative stress-induced ischemic injury and suggest that targeting the Nrf2/ARE pathway may be a promising approach for therapeutic intervention in stroke.
Keywords
RT-PCRHeme oxygenase-1NQO-1AEBSFnuclear factor erythroid-2-related factor 2γ-GCSMCAOOGDEAAT3PMSFDCFH-DAHO-1NAD(P)H:quinine oxidoreductase 1Nrf2ICAGSHECA2′,7′-dichlorodihydrofluorescein diacetate3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromideMTTROSAstrocyteEDTAEdetic acidmiddle cerebral artery occlusionCerebral ischemiaBenzamidineTerminal deoxynucleotidyl transferase dUTP nick end labelingTUNELexcitatory amino acid transporter 3external carotid arteryinternal carotid arteryantioxidant response elementphenylmethylsulfonyl fluorideOxygen and glucose deprivationAREHematoxylin and EosinGlutathioneReactive oxygen species
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Authors
Xu Jing, Dongmei Ren, Xinbing Wei, Huanying Shi, Xiumei Zhang, Ruth G. Perez, Haiyan Lou, Hongxiang Lou,