Neurochemical research
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Neurochemical research · Feb 2018
Resveratrol Attenuates the Cytotoxicity Induced by Amyloid-β1-42 in PC12 Cells by Upregulating Heme Oxygenase-1 via the PI3K/Akt/Nrf2 Pathway.
Oxidative stress and cytotoxic damage induced by amyloid beta (Aβ) have been considered pivotal in the pathogenesis of Alzheimer's disease (AD) and may represent a target for treatment. The phosphatidylinositol 3-kinase (PI3K)/Akt pathway elicits a survival signal to protect against multiple injuries, and the transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2), a downstream target of the PI3K/Akt pathway, can bind to HO-1. Resveratrol, a natural polyphenol derived from grapes, has been widely reported to have diverse antioxidative effects against AD, but the mechanisms have not been fully elucidated. ⋯ More importantly, resveratrol stimulated the activation of HO-1, Nrf2, PI3K, and phosphorylated Akt. Notably, the neuroprotective effects of resveratrol were eliminated by the HO-1 inhibitor zinc protoporphyrin IX (ZnPP), Nrf2 small interfering RNA (siRNA), and the PI3K/Akt inhibitor LY294002. Taken together, the findings suggest that the cytoprotection of resveratrol against the cytotoxicity induced by Aβ1-42 in PC12 cells is through the upregulation of HO-1 expression via the activation of the PI3K/AKT/Nrf2 intracellular signaling pathway, which might provide novel insights for understanding the mechanism of the neuroprotective effect of resveratrol as an anti-AD drug.