Journal
EUROPEAN JOURNAL OF PHARMACOLOGY
Volume 658, Issue 2-3, Pages 84-90Publisher
ELSEVIER
DOI: 10.1016/j.ejphar.2011.02.028
Keywords
Alzheimer's disease; Apoptosis; Nrf2; Oxazine derivative; Oxidative stress; PC12 cells
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Funding
- Shahid Beheshti University of Medical Sciences
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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.
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