Resveratrol pretreatment attenuates injury and promotes proliferation of neural stem cells following oxygen-glucose deprivation/reoxygenation by upregulating the expression of Nrf2, HO-1 and NQO1 in vitro

Abstract

There is considerable interest in the use of drugs and other methods for protecting implanted neural stem cells (NSCs) from the adverse environment of injured tissue for successful cell therapy. Resveratrol can modify cardiac stem cells to enhance their survival and differentiation, however, its effect and the mechanism underlying its neuroprotective effect on NSCs following stroke remain to be fully elucidated. Nuclear factor erythroid 2-related factor 2 (Nrf-2) signaling is important in antioxidative stress, and the role of Nrf-2 signaling in the enhanced neuroprotection of NSCs by resveratrol following stroke also remains to be elucidated. In the present study, NSCs were pretreated with resveratrol prior to oxygen-glucose deprivation/reoxygenation (OGD/R) in vitro. The survival, apoptosis and proliferation of the NSCs were assessed using an MTT assay, Hoechst 33258 staining of nuclei and flow cytometry, respectively. In addition, the activity of superoxide dismutase (SOD), level of malondiadehyde (MDA) and content of glutathione (GSH) were determined. The protein expressions levels of Nrf-2, NAD(P)H:quinone oxidoreductase 1 (NQO-1), and heme oxygenase 1 (HO-1) were detected using western blot analysis. It was found that resveratrol markedly enhanced NSC survival and proliferation, decreased apoptosis and the levels of MDA, and increased the activity of SOD and content of GSH in a concentration-dependent manner following OGD/R injury in vitro. In addition, the protein expression levels of Nrf2, HO-1 and NQO1 were significantly upregulated. These findings suggested that resveratrol attenuated injury and promoted proliferation of the NSCs, at least in part, by upregulating the expression of Nrf2, HO-1 and NQO1 following OGD/R injury in vitro.