Apocynin attenuates cholesterol oxidation product-induced programmed cell death by suppressing NF-κB-mediated cell death process in differentiated PC12 cells

Neurochem Int. 2015 Oct:89:28-39. doi: 10.1016/j.neuint.2015.06.012. Epub 2015 Jun 26.

Abstract

Cholesterol oxidation products are suggested to be involved in neuronal degeneration. Apocynin has demonstrated to have anti-inflammatory and anti-oxidant effects. We assessed the effect of apocynin on the cholesterol oxidation product-induced programmed cell death in neuronal cells using differentiated PC12 cells in relation to NF-κB-mediated cell death process. 7-Ketocholesterol and 25-hydroxycholesterol decreased the levels of Bid and Bcl-2, increased the levels of Bax and p53, and induced loss of the mitochondrial transmembrane potential, release of cytochrome c and activation of caspases (-8, -9 and -3). 7-Ketocholesterol caused an increase in the levels of cytosolic and nuclear NF-κB p65, cytosolic NF-κB p50 and cytosolic phospho-IκB-α, which was inhibited by the addition of 0.5 μM Bay11-7085 (an inhibitor of NF-κB activation). Apocynin attenuated the cholesterol oxidation product-induced changes in the programmed cell death-related protein levels, NF-κB activation, production of reactive oxygen species, and depletion of GSH. The results show that apocynin appears to attenuate the cholesterol oxidation product-induced programmed cell death in PC12 cells by suppressing the activation of the mitochondrial pathway and the caspase-8- and Bid-dependent pathways that are mediated by NF-κB activation. The preventive effect appears to be associated with the inhibitory effect on the production of reactive oxygen species and depletion of GSH.

Keywords: Apocynin; Cell protection; Cholesterol oxidation products; Differentiated PC12 cells; NF-κB activation; Programmed cell death-related proteins.

MeSH terms

  • Acetophenones / pharmacology*
  • Animals
  • Antioxidants / pharmacology*
  • Cell Death / drug effects
  • Cell Death / physiology
  • Cell Differentiation / drug effects*
  • Cell Differentiation / physiology
  • Cytochromes c / antagonists & inhibitors
  • Cytochromes c / metabolism
  • Hydroxycholesterols / antagonists & inhibitors*
  • Hydroxycholesterols / metabolism
  • NF-kappa B / antagonists & inhibitors*
  • NF-kappa B / metabolism
  • Oxidation-Reduction / drug effects
  • PC12 Cells
  • Rats
  • Reactive Oxygen Species / antagonists & inhibitors
  • Reactive Oxygen Species / metabolism

Substances

  • Acetophenones
  • Antioxidants
  • Hydroxycholesterols
  • NF-kappa B
  • Reactive Oxygen Species
  • 25-hydroxycholesterol
  • Cytochromes c
  • acetovanillone