Quercetin-3-O-(2″-galloyl)-α-L-rhamnopyranoside attenuates cholesterol oxidation product-induced apoptosis by suppressing NF-κB-mediated cell death process in differentiated PC12 cells

Naunyn Schmiedebergs Arch Pharmacol. 2015 Aug;388(8):869-81. doi: 10.1007/s00210-015-1120-7. Epub 2015 Apr 7.

Abstract

Cholesterol oxidation products are suggested to be involved in neuronal cell degeneration. We examined the preventive effect of quercetin-3-O-(2″-galloyl)-α-L-rhamnopyranoside (QGR), a quercetin derivative, on the cholesterol oxidation product-induced neuronal cell death using differentiated PC12 cells in relation to nuclear factor (NF)-κB-mediated apoptotic process. 7-Ketocholesterol and 25-hydroxycholesterol induced a decrease in the levels of BH3 interacting-domain death agonist (Bid) and B cell lymphoma 2 (Bcl-2), increase in the levels of Bcl-2-associated X protein (Bax) and p53, loss of the mitochondrial transmembrane potential, cytochrome c release, activation of caspases, and cleavage of poly(ADP-ribose) polymerase 1 (PARP-1). 7-Ketocholesterol induced increase in cytosolic and nuclear NF-κB p65, nuclear phospho-NF-κB p65, cytosolic NF-κB p50, and cytosolic phospho-IκB-α levels. The addition of QGR, N-acetyl cysteine, or Bay 11-7085 attenuated the cholesterol oxidation product-induced changes in the apoptosis-related protein levels, activation of NF-κB, formation of reactive oxygen species, depletion of glutathione (GSH), nuclear damage, and cell death. The results show that QGR may attenuate the cholesterol oxidation product-induced apoptosis in PC12 cells by suppressing the activation of the mitochondrial pathway and the caspase-8- and Bid-dependent pathways that is mediated by NF-κB activation. The preventive effect appears to be associated with the inhibitory effect on the formation of reactive oxygen species and depletion of GSH.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Apoptosis Regulatory Proteins / metabolism
  • Cell Death / drug effects
  • Cell Survival / drug effects
  • DNA Fragmentation
  • Glutathione / metabolism
  • Hydroxycholesterols / toxicity*
  • Ketocholesterols / toxicity*
  • Membrane Potential, Mitochondrial / drug effects
  • NF-kappa B / metabolism
  • Oxidation-Reduction
  • PC12 Cells
  • Quercetin / analogs & derivatives*
  • Quercetin / pharmacology
  • Rats
  • Reactive Oxygen Species / metabolism

Substances

  • Apoptosis Regulatory Proteins
  • Hydroxycholesterols
  • Ketocholesterols
  • NF-kappa B
  • Reactive Oxygen Species
  • quercetin 3-O-beta-(2''-galloyl)-rhamnopyranoside
  • 25-hydroxycholesterol
  • Quercetin
  • Glutathione
  • 7-ketocholesterol