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3,4,5-Tricaffeoylquinic Acid Attenuates Proteasome Inhibition-Mediated Programmed Cell Death in Differentiated PC12 cells

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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.

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Acknowledgments

This research was supported by the Chung-Ang University Research Scholarship Grants in 2014, Chung-Ang University, Seoul, South Korea, and the Grant of the BK21plus Skin Barrier Network Human Resources Development Team, National Research Foundation of Korea, Ministry of Education, Republic of Korea.

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Authors and Affiliations

  1. 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 Nam, Da Hee Lee, Yun Jeong Kim, Yong Kyoo Shin & Chung Soo Lee

  2. Department of Thoracic and Cardiovascular Surgery, Chung-Ang University Hospital, Seoul, 156-755, South Korea

    Dong Suep Sohn

  3. Department of Internal Medicine, SoonChunHyang University Hospital, Bucheon City, Kyung-Gi-Do, 420-767, South Korea

    Min Sung Lee

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  1. Yoon Jeong Nam
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Nam, Y.J., Lee, D.H., Kim, Y.J. et al. 3,4,5-Tricaffeoylquinic Acid Attenuates Proteasome Inhibition-Mediated Programmed Cell Death in Differentiated PC12 cells. Neurochem Res 39, 1416–1425 (2014). https://doi.org/10.1007/s11064-014-1327-x

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