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Archives of Toxicology

, Volume 92, Issue 2, pp 669–677 | Cite as

Protective effects of the resveratrol analog piceid in dopaminergic SH-SY5Y cells

  • Sneha Potdar
  • Mayur S. Parmar
  • Sidhartha D. Ray
  • Jane E. Cavanaugh
Molecular Toxicology

Abstract

Age-related motor deficits, such as loss of balance and coordination, are caused, in part, by loss of dopaminergic neurons. Oxidative stress is known to play a role in this neuronal loss. Resveratrol, a natural antioxidant with anticancer and anti-inflammatory potential, has been shown to protect dopaminergic-like cells (SH-SY5Y) against oxidative stress. However, the low bioavailability of resveratrol makes it worthwhile to explore newer compounds with similar properties. Piceid (RV8), an analog of resveratrol, has greater bioavailability than resveratrol, and our studies found that piceid (10, 20, 30 µM) protects SH-SY5Y cells against oxidative stress. Our investigations also found that the neuroprotection afforded by piceid was decreased when the MAP kinases, ERK1/2 and ERK5, were independently inhibited. Since oxidative stress is considered a master operator of apoptosis, our study also scrutinized dopamine-induced apoptosis and whether caspase-3/7 and Bcl-2 are involved, following piceid pretreatment followed by dopamine exposure. Our findings suggested that piceid pretreatment inhibited the dopamine-induced increase in caspase-3/7 activity and dopamine-induced loss of Bcl-2 expression. Overall, these findings suggest that the neuroprotective effects of piceid are mediated via the activation of ERK1/2, ERK5, and inhibition of apoptosis caused by oxidative stress.

Keywords

Piceid Polydatin Resveratrol Phytochemicals Antioxidant Apoptosis Oxidative stress Toxicity caspase Bcl-2 ERK1/2 ERK5 Dopamine SH-SY5Y 

Notes

Acknowledgements

This work was supported by the Department of Pharmacology and Toxicology at the Graduate School of Pharmaceutical Sciences, Duquesne University and did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Compliance with ethical standards

Conflict of interest

The authors have no conflict of interest to declare.

Supplementary material

204_2017_2073_MOESM1_ESM.tiff (251 kb)
Supplementary material 1 (TIFF 250 kb) Figure S1 Piceid (RV8) pretreatment did not significantly affect the ratio of cleaved caspase 9/caspase 9 following DA-treatment in SH-SY5Y cells. Quantification of the ratio of cleaved caspase 9/caspase 9 immunoblots using Licor Odyssey software. The values are calculated using the integrated intensity. Data are expressed as mean ± standard error of the mean
204_2017_2073_MOESM2_ESM.tiff (852 kb)
Supplementary material 2 (TIFF 852 kb) Figure S2 Piceid (RV8) protects against DA-induced toxicity in SH-SY5Y cells. SH-SY5Y cells were pretreated with indicated concentrations of piceid (1 h) with DA. Each experiment was performed 3 independent times and data is presented as mean ± standard error of mean. Statistical analysis was applied using one-way ANOVA followed by Dunnett’s post hoc test. *p < 0.05, **p < 0.01. # indicates compared to vehicle while * and n.s. indicate compared to 150 μM DA
204_2017_2073_MOESM3_ESM.tiff (1.5 mb)
Supplementary material 3 (TIFF 1521 kb) Figure S3 Structure of piceid (RV8) showing stereochemistry of the compound
204_2017_2073_MOESM4_ESM.tiff (730 kb)
Supplementary material 4 (TIFF 729 kb) Figure S4 Piceid (RV8) pretreatment attenuates DA-mediated increase in caspase 3/7 activity in SH-SY5Y cells SH-SY5Y cells were pretreated with indicated concentrations of piceid (1 h) with or without DA. Actual fluorescence values (arbitrary units) of caspase 3/7 activity are shown. Each experiment was performed 3 independent times and data is presented as mean ± standard error of mean. Statistical analysis was applied using one-way ANOVA followed by Dunnett’s post hoc test. ***p < 0.001, ****p < 0.0001. # indicates compared to vehicle while * indicates compared to 150 μM DA

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Copyright information

© Springer-Verlag GmbH Germany 2017

Authors and Affiliations

  1. 1.Division of Pharmaceutical Sciences, Department of Pharmacology, Mylan School of PharmacyDuquesne UniversityPittsburghUSA
  2. 2.Department of Pharmaceutical SciencesManchester University College of Pharmacy, Natural and Health SciencesFort WayneUSA

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