Accumulating evidence has shown that astrocytes play a critical role in neuroinflammation and protection against oxidative stress. In this study, we investigated the effects of sigma-1 receptor (Sig-1R) activation on lipopolysaccharide (LPS)-induced inflammatory reactions and oxidative/nitrosative stress in cultured astrocytes. We found that SA4503, a selective Sig-1R agonist, attenuated LPS-induced inflammatory reactions and oxidative/nitrosative stress by downregulating the expression of iNOS and tumor necrosis factor α (TNF-α) and upregulating glutathione (GSH) in cultured astrocytes. To investigate the mechanism by which SA4503 caused these effects, we then examined the expression of nuclear factor erythroid-derived 2-like 2 (Nrf2) and heme oxygenase-1 (HO-1) through western blotting. The results revealed that SA4503 treatment increased Nrf2 and HO-1 expression significantly. These results suggested that the antioxidative/nitrosative stress and anti-inflammatory effects of Sig-1R activation in astrocytes were partially mediated by Nrf2 and HO-1 activation.
Keywords: Astrocytes; Nrf2/HO-1 signaling; Sig-1R; oxidative/nitrosative stress.
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