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Endoplasmic Reticulum Stress–Induced Cell Death in Dopaminergic Cells: Effect of Resveratrol

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Abstract

Resveratrol, a naturally occurring polyphenol, exhibits antioxidant, antiaging, and anticancer activity. Resveratrol has also been shown to inhibit tumor initiation, promotion, and progression in a variety of cell culture systems. Earlier, we showed that paraquat, a bipyridyl herbicide, triggers endoplasmic reticulum stress, cell dysfunction, and dopaminergic cell death. Due to its antioxidant activity, we assessed the ability of resveratrol to rescue cells from the toxic effects of paraquat. While resveratrol did not have any protective effect at low concentrations, it triggered endoplasmic reticulum (ER) stress-induced cell death at higher concentrations (50–250 μM). The present study was carried out to determine the mechanism by which resveratrol triggers ER stress and cell death in dopaminergic N27 cells. Our studies demonstrate that resveratrol triggers ER stress and cell dysfunction, caspase activation, p23 cleavage and inhibition of proteasomal activity in dopaminergic N27 cells. While over expression of uncleavable p23 was associated with decreased cell death, downregulation of p23 protein expression by siRNA resulted in enhancement of ER stress-induced cell death triggered by resveratrol indicating a protective role for the small co-chaperone p23 in dopaminergic cell death.

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Abbreviations

ER:

endoplasmic reticulum

pcd:

programmed cell death

eIF2α:

eukaryotic initiation factor-2 alpha

GRP:

glucose-regulated protein

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Acknowledgements

We thank members of the Bredesen laboratory and Andersen laboratory for helpful comments and discussions and Molly Susag for administrative assistance. This work was supported by grants from the National Institutes of Health NS33376 to D.E.B. and R.V.R.

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Authors and Affiliations

  1. The Buck Institute for Age Research, 8001 Redwood Blvd., Novato, CA, 94945, USA

    Shankar J. Chinta, Karen S. Poksay, Matthew Hart, Dale E. Bredesen, Julie K. Andersen & Rammohan V. Rao

  2. Marin Academy, 1600 Mission Ave, San Rafael, CA, 94901, USA

    Gaayatri Kaundinya

  3. University of California, San Francisco, CA, 94143, USA

    Dale E. Bredesen

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  1. Shankar J. Chinta
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  2. Karen S. Poksay
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Correspondence to Julie K. Andersen or Rammohan V. Rao.

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Chinta, S.J., Poksay, K.S., Kaundinya, G. et al. Endoplasmic Reticulum Stress–Induced Cell Death in Dopaminergic Cells: Effect of Resveratrol. J Mol Neurosci 39, 157–168 (2009). https://doi.org/10.1007/s12031-008-9170-7

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