Attenuation of LPS-induced apoptosis in NGF-differentiated PC12 cells via NF-κB pathway and regulation of cellular redox status by an oxazine derivative

Biochimie. 2011 May;93(5):899-908. doi: 10.1016/j.biochi.2011.01.012. Epub 2011 Feb 2.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antioxidants / pharmacology*
  • Apoptosis / drug effects*
  • Caspase 3 / metabolism
  • Catalase / metabolism
  • Cell Differentiation / drug effects
  • Cell Survival / drug effects
  • Cyclooxygenase 2 / metabolism
  • Glutamate-Cysteine Ligase / metabolism
  • Heat-Shock Proteins / metabolism
  • Lipid Peroxidation / drug effects
  • Lipopolysaccharides / pharmacology*
  • NF-E2-Related Factor 2 / metabolism
  • NF-kappa B / metabolism*
  • Nerve Growth Factor / pharmacology
  • Neurons / cytology*
  • Neurons / drug effects
  • Neurons / metabolism
  • Nitric Oxide / metabolism
  • Oxazines / pharmacology*
  • Oxidation-Reduction
  • PC12 Cells
  • Protein Transport / drug effects
  • Rats
  • Reactive Oxygen Species / metabolism
  • Signal Transduction / drug effects*
  • Superoxide Dismutase / metabolism
  • bcl-2-Associated X Protein / metabolism
  • bcl-Associated Death Protein / metabolism

Substances

  • 2-ethoxy-4,5-diphenyl-1,3-oxazine-6-one
  • Antioxidants
  • Heat-Shock Proteins
  • Lipopolysaccharides
  • NF-E2-Related Factor 2
  • NF-kappa B
  • Nfe2l2 protein, rat
  • Oxazines
  • Reactive Oxygen Species
  • bcl-2-Associated X Protein
  • bcl-Associated Death Protein
  • Nitric Oxide
  • Nerve Growth Factor
  • Catalase
  • Cyclooxygenase 2
  • Superoxide Dismutase
  • Caspase 3
  • Glutamate-Cysteine Ligase