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.
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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.
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Conflict of interest
The authors have no conflict of interest to declare.
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
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
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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