SENP1-mediated NEMO de-SUMOylation inhibits intermittent hypoxia induced inflammatory response of microglia in vitro.

Abstract

Among the seven small ubiquitin-like modifier (SUMO)-specific proteases (SENPs), our previous work showed that SENP1 suppressed nuclear factor kappa B (NF-κB) activation and alleviates the inflammatory response in microglia. However, the mechanism is still largely unknown. In this study, western blot analysis and enzyme-linked immunosorbent assay were utilized for evaluating the extent of NF-κB activation and expression of proinflammatory cytokines. qPCR and western blot analysis were performed to detect SENP1 expression. Coimmunoprecipitation followed by western blot analysis was applied to measure the changes in SUMOylation of NF-κB essential modulator (NEMO) and P65 in microglia with or without overexpression of SENP1. As the results, we found that intermittent hypoxia (IH) triggered the activation of NF-κB and upregulated the expression levels of tumor necrosis factor-α and interleukin-6. Interestingly, our data indicated that the SUMOylation of NEMO was enhanced by IH while SUMOylation of P65 was not affected. Further, our data showed that overexpression of SENP1 could decrease the extent of NF-κB activation and inhibit the inflammatory response of microglia through regulating the SUMOylation of NEMO. Collectively, this study presents the first report of the SENP1-controlled de-SUMOylation process of NEMO and its critical role in regulating NF-κB activation and proinflammatory cytokines secretion in microglia cells. This study would benefit for clarifying the role of SENP1 in IH-induced activation of microglia, thus providing potential therapeutic targets for obstructive sleep apnea treatment.