The objective of this study was to investigate the effect of resveratrol (a natural polyphenolic phytostilbene) on tau hyperphosphorylation and oxidative damage induced by sodium orthovanadate (Na3VO4), the prevalent species of vanadium (vanadate), in rat hippocampal slices. Our results showed that resveratrol significantly inhibited Na3VO4-induced hyperphosphorylation of tau at the Ser396 (p-S396-tau) site, which is upregulated in the hippocampus of Alzheimer's disease (AD) brains and principally linked to AD-associated cognitive dysfunction. Subsequent mechanistic studies revealed that reduction of ERK1/2 activation was involved in the inhibitory effect of resveratrol by inhibiting the ERK1/2 pathway with SL327 mimicking the aforementioned effect of resveratrol. Moreover, resveratrol potently induced GSK-3β Ser9 phosphorylation and reduced Na3VO4-induced p-S396-tau levels, which were markedly replicated by pharmacologic inhibition of GSK-3β with LiCl. These results indicate that resveratrol could suppress Na3VO4-induced p-S396-tau levels via downregulating ERK1/2 and GSK-3β signaling cascades in rat hippocampal slices. In addition, resveratrol diminished the increased extracellular reactive oxygen species generation and hippocampal toxicity upon long-term exposure to Na3VO4 or FeCl2. Our findings strongly support the notion that resveratrol may serve as a potential nutraceutical agent for AD.
Bibliographical noteFunding Information:
*Phone: 82-2-2650-5739. Fax: 82-2-2653-8891. E-mail: firstname.lastname@example.org *Phone: 82-2-2650-5823. Fax: 82-2-2653-8891. E-mail: email@example.com. ORCID Hee-Sun Kim: 0000-0003-1889-8739 Young Hae Chong: 0000-0001-6311-0619 Funding This research was supported by the Basic Science Research Program through the National Research Foundation (NRF) and funded by the Ministry of Science, ICT & Future Planning, Republic of Korea (Grant Nos. NRF-2010-0027945 and NRF-2015R1A2A2A01005226). Notes The authors declare no competing financial interest.
© 2017 American Chemical Society.
- Alzheimer's disease
- oxidative damage