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Flavanonol Taxifolin Attenuates Proteasome Inhibition-Induced Apoptosis in Differentiated PC12 Cells by Suppressing Cell Death Process

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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.

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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.

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Authors and Affiliations

  1. Department of Pharmacology, College of Medicine, and the BK21plus Skin Barrier Network Human Resources Development Team, Chung-Ang University, Seoul, 156-756, South Korea

    Yoon Jeong Nam, Da Hee Lee, 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

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Correspondence to Chung Soo Lee.

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Nam, Y.J., Lee, D.H., Shin, Y.K. et al. Flavanonol Taxifolin Attenuates Proteasome Inhibition-Induced Apoptosis in Differentiated PC12 Cells by Suppressing Cell Death Process. Neurochem Res 40, 480–491 (2015). https://doi.org/10.1007/s11064-014-1493-x

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