3,4,5-tricaffeoylquinic acid attenuates proteasome inhibition-mediated programmed cell death in differentiated PC12 cells.
The dysfunction of the proteasome system is suggested to be implicated in neuronal degeneration. Caffeoylquinic acid derivatives have demonstrated anti-oxidant and anti-inflammatory effects. However, the effect of 3,4,5-tricaffeoylquinic acid 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 3,4,5-tricaffeoylquinic acid on the proteasome inhibition-induced programmed cell death 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), and an increase in the tumor suppressor p53 levels. Treatment with 3,4,5-tricaffeoylquinic acid attenuated the proteasome inhibitor-induced changes in the programmed cell death-related protein levels, formation of reactive oxygen species, GSH depletion and cell death. The results show that 3,4,5-tricaffeoylquinic acid may attenuate the proteasome inhibitor-induced programmed cell death in PC12 cells by suppressing the activation of the mitochondrial pathway and the caspase-8- and Bid-dependent pathways. The preventive effect of 3,4,5-tricaffeoylquinic acid appears to be attributed to its inhibitory effect on the formation of reactive oxygen species and depletion of GSH.
Department of Pharmacology, College of Medicine, and the BK21(plus) Skin Barrier Network Human Resources Development Team, Chung-Ang University, Seoul, 156-756, South Korea.
Yoon Jeong
YJ
Nam
Da Hee
DH
Lee
Yun Jeong
YJ
Kim
Yong Kyoo
YK
Shin
Dong Suep
DS
Sohn
Min Sung
MS
Lee
Chung Soo
CS
Lee
D000818:Animals; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D002454:Cell Differentiation / Q000187:drug effects* / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects / Q000502:physiology; D016716:PC12 Cells; D061988:Proteasome Inhibitors / Q000494:pharmacology*; D011801:Quinic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism
D015853:Cysteine Proteinase Inhibitors; D061988:Proteasome Inhibitors; D017382:Reactive Oxygen Species; C472707:caffeoylquinic acid; D011801:Quinic Acid