3,4,5-tricaffeoylquinic acid attenuates proteasome inhibition-mediated programmed cell death in differentiated PC12 cells.

Abstract

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.

• Authors: Yoon Jeong Nam, Da Hee Lee, Yun Jeong Kim, Yong Kyoo Shin, Dong Suep Sohn, Min Sung Lee, Chung Soo Lee
• Journal: Neurochemical research (Neurochem Res) Vol. 39 Issue 8 Pg. 1416-25 (Aug 2014) ISSN: 1573-6903 [Electronic] United States
• PMID: 24825618 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cysteine Proteinase Inhibitors
• Proteasome Inhibitors
• Reactive Oxygen Species
• caffeoylquinic acid
• Quinic Acid

Topics

• Animals
• Cell Death (drug effects, physiology)
• Cell Differentiation (drug effects, physiology)
• Cell Survival (drug effects, physiology)
• Cysteine Proteinase Inhibitors (pharmacology)
• Dose-Response Relationship, Drug
• Membrane Potential, Mitochondrial (drug effects, physiology)
• PC12 Cells
• Proteasome Inhibitors (pharmacology)
• Quinic Acid (analogs & derivatives, pharmacology)
• Rats
• Reactive Oxygen Species (metabolism)