title: Attenuation of LPS-induced apoptosis in NGF-differentiated PC12 cells via NF-κB pathway and regulation of cellular redox status by an oxazine derivative.
abstract: Neuronal cell death due to apoptosis is a common characteristic of neurodegenerative diseases. In this study, we report protective effect of 2-ethoxy-4,5-diphenyl-1,3-oxazine-6-one (EDPOO) against lipopolysaccharide (LPS)-induced cell death in rat pheochromocytoma (PC12) cells, as assessed by MTT test, acridine orange/ethidium bromide staining, determination of Bax, Bcl-2 and caspase-3 levels. We further show that this compound could increase heat shock proteins Hsp-70 and Hsp-32 levels. EDPOO also modulates nuclear levels of Nrf2 and NF-κB, transcription factors that are activated by intracellular reactive oxygen species and/or mediators generated due to chemical exposure of cells. Pretreatment of the cells with this oxazine derivative also increases γ-GCS level, as well as antioxidant enzyme activities, in a dose-dependent manner. Protective effect of this compound could represent a promising approach for treatment of neurodegenerative diseases.
authors.affiliation: Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Niloufar
authors.initials: N
authors.lastname: Ansari
authors.forename: Fariba
authors.initials: F
authors.lastname: Khodagholi
authors.forename: Mohsen
authors.initials: M
authors.lastname: Amini
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Shaerzadeh
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D002374:Catalase / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D051546:Cyclooxygenase 2 / Q000378:metabolism; D005721:Glutamate-Cysteine Ligase / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008070:Lipopolysaccharides / Q000494:pharmacology*; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D020932:Nerve Growth Factor / Q000494:pharmacology; D009474:Neurons / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D010078:Oxazines / Q000494:pharmacology*; D010084:Oxidation-Reduction; D016716:PC12 Cells; D021381:Protein Transport / Q000187:drug effects; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D013482:Superoxide Dismutase / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism; D051025:bcl-Associated Death Protein / Q000378:metabolism
chemical_list: C559680:2-ethoxy-4,5-diphenyl-1,3-oxazine-6-one; D000975:Antioxidants; D006360:Heat-Shock Proteins; D008070:Lipopolysaccharides; D051267:NF-E2-Related Factor 2; D016328:NF-kappa B; C495637:Nfe2l2 protein, rat; D010078:Oxazines; D017382:Reactive Oxygen Species; D051028:bcl-2-Associated X Protein; D051025:bcl-Associated Death Protein; D009569:Nitric Oxide; D020932:Nerve Growth Factor; D002374:Catalase; D051546:Cyclooxygenase 2; D013482:Superoxide Dismutase; D053148:Caspase 3; D005721:Glutamate-Cysteine Ligase