title: Flavanonol taxifolin attenuates proteasome inhibition-induced apoptosis in differentiated PC12 cells by suppressing cell death process.
abstract: The proteasomal dysfunction and mitochondrial impairment has been implicated in neuronal degeneration. Taxifolin has antioxidant and anti-inflammatory effects. However, the effect of taxifolin on the neuronal cell death induced by proteasome inhibition has not been studied. Therefore, in the respect of cell death process, we assessed the effect of taxifolin on the proteasome inhibition-induced apoptosis in neuronal cell injury using differentiated PC12 cells. The proteasome inhibitors MG132 and MG115 induced a decrease in Bid, Bcl-2, and survivin protein levels, an increase in Bax, loss of the mitochondrial transmembrane potential, cytochrome c release, activation of caspases(-8, -9 and -3), an increase in the tumor suppressor p53 levels and cleavage of PARP-1. The addition of taxifolin attenuated the proteasome inhibitor-induced changes in the apoptosis-related protein levels, formation of reactive oxygen species, depletion and oxidation of GSH, formations of malondialdehyde and carbonyls, and cell death. The results show that taxifolin may attenuate the proteasome inhibitor-induced apoptosis in PC12 cells by suppressing the activation of the mitochondrial pathway and the caspase-8- and Bid-dependent pathways. The preventive effect of taxifolin appears to be attributed to its inhibitory effect on the formation of reactive oxygen species, and depletion and oxidation 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: Yoon Jeong
authors.initials: YJ
authors.lastname: Nam
authors.forename: Da Hee
authors.initials: DH
authors.lastname: Lee
authors.forename: Yong Kyoo
authors.initials: YK
authors.lastname: Shin
authors.forename: Dong Suep
authors.initials: DS
authors.lastname: Sohn
authors.forename: Chung Soo
authors.initials: CS
authors.lastname: Lee
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D002454:Cell Differentiation / Q000187:drug effects* / Q000502:physiology; D044948:Flavonols / Q000494:pharmacology; D016716:PC12 Cells; D061988:Proteasome Inhibitors / Q000633:toxicity*; D011794:Quercetin / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D044948:Flavonols; D061988:Proteasome Inhibitors; D017382:Reactive Oxygen Species; D011794:Quercetin; C003377:taxifolin