Back to Search
Start Over
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
- Source :
- Naunyn-Schmiedeberg's archives of pharmacology. 388(8)
- Publication Year :
- 2015
-
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.
- Subjects :
- Programmed cell death
Cell Survival
Apoptosis
DNA Fragmentation
PC12 Cells
chemistry.chemical_compound
Animals
Ketocholesterols
Caspase
Pharmacology
chemistry.chemical_classification
Membrane Potential, Mitochondrial
Reactive oxygen species
biology
Cell Death
Cytochrome c
NF-kappa B
NF-κB
General Medicine
Glutathione
Molecular biology
Hydroxycholesterols
Cell biology
Rats
Cytosol
chemistry
biology.protein
Quercetin
Apoptosis Regulatory Proteins
Reactive Oxygen Species
Oxidation-Reduction
Subjects
Details
- ISSN :
- 14321912
- Volume :
- 388
- Issue :
- 8
- Database :
- OpenAIRE
- Journal :
- Naunyn-Schmiedeberg's archives of pharmacology
- Accession number :
- edsair.doi.dedup.....10a8b954a2435979c03f49c101fab55c