title: 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.
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.
authors.affiliation: Department of Pharmacology, College of Medicine, and the BK21plus Skin Barrier Network Human Resources Development Team, Chung-Ang University, Seoul, 156-756, South Korea.
authors.forename: Da Hee
authors.initials: DH
authors.lastname: Lee
authors.forename: Yoon Jeong
authors.initials: YJ
authors.lastname: Nam
authors.forename: Chung Soo
authors.initials: CS
authors.lastname: Lee
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D053938:DNA Fragmentation; D005978:Glutathione / Q000378:metabolism; D006888:Hydroxycholesterols / Q000633:toxicity*; D007653:Ketocholesterols / Q000633:toxicity*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D016328:NF-kappa B / Q000378:metabolism; D010084:Oxidation-Reduction; D016716:PC12 Cells; D011794:Quercetin / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D051017:Apoptosis Regulatory Proteins; D006888:Hydroxycholesterols; D007653:Ketocholesterols; D016328:NF-kappa B; D017382:Reactive Oxygen Species; C523166:quercetin 3-O-beta-(2''-galloyl)-rhamnopyranoside; C007997:25-hydroxycholesterol; D011794:Quercetin; D005978:Glutathione; C003001:7-ketocholesterol
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