2-Ethoxy-4,5-diphenyl-1,3-oxazine-6-one activates the Nrf2/HO-1 axis and protects against oxidative stress-induced neuronal death
2-Ethoxy-4,5-diphenyl-1,3-oxazine-6-one activates the Nrf2/HO-1 axis and protects against oxidative stress-induced neuronal death
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DOI：
10.1016/j.ejphar.2011.02.028
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发表时间：
2011-05-11
影响因子：
5
通讯作者：
Amini, Mohsen
中科院分区：
文献类型：
--
作者：
Ansari, Niloufar;Khodagholi, Fariba;Amini, Mohsen
细胞凋亡或程序性细胞死亡被认为是阿尔茨海默病发病机制中神经退行性变的重要模式。本研究探讨了2-乙氧基-4,5-二苯基-1 -1,3-恶嗪-6-one （EDPOO）对h2o2诱导的大鼠嗜铬细胞瘤（PC12）细胞死亡的神经保护作用。通过MTT实验、吖啶橙/溴化乙啶染色和caspase-3表达实验，我们发现H2O2触发了一系列细胞级联反应，导致细胞死亡，而用这种恶嗪衍生物预处理细胞可减轻细胞凋亡的程度。我们进一步发现，EDPOO通过提高Hsp-70水平、稳定Nrf2、上调HO-1和γ - gcs来发挥其神经保护作用。此外，这种恶嗪衍生物通过上调抗氧化酶来调节细胞氧化还原状态。该化合物的神经保护作用可能为神经退行性疾病的治疗提供新的潜在应用。(C) 2011 Elsevier B.V.版权所有
Apoptosis or programmed cell death has been suggested as an important mode of neurodegeneration in Alzheimer's disease pathogenesis. The present study explored the neuroprotective effect of 2-ethoxy-4,5-dipheny1-1,3-oxazine-6-one (EDPOO) against H2O2-induced cell death in rat pheochromocytoma (PC12) cells. We found that H2O2 triggered a range of cellular cascades which leads to cell death, whereas pretreatment of the cells with this oxazine derivative attenuated the extent of apoptosis, as assessed by MTT assay, acridine orange/ethidium bromide staining and caspase-3 expression assay. We further showed that EDPOO exerts its neuroprotective effect by enhancing Hsp-70 level, stabilizing Nrf2 and upregulation of HO-1 and gamma-GCS. Moreover, this oxazine derivative regulated cellular redox status via antioxidant enzyme upregulation. The neuroprotective effect of this compound may provide a new potential application for the treatment of neurodegenerative diseases. (C) 2011 Elsevier B.V. All rights reserved.