Sodium Danshensu ameliorates cerebral ischemia/reperfusion injury by inhibiting CLIC4/NLRP3 inflammasome ‐mediated endothelial cell pyroptosis

Mechanism of SDSS in inhibiting endothelial cell pyroptosis. In the priming step, NLRP3, pro-Caspase-1, GSDMD-full, pro-IL-1 β, and pro-IL-18 were up-regulated. Furthermore, the translocation of CLIC4 from cytoplasm to the membrane induced chloride outflow, resulting in the assembly of NLRP3, ASC and Pro-Caspase-1 into a platform (activation step). By binding CLIC4 and blocking its membrane localization, SDSS inhibited c hloride outflow, thus inhibiting the activation of NLRP3 inflammasome and then the cleavage of pro-Caspase-1 into Caspase-1. This inhibited pyroptosis along with the release of IL-1β and IL-18, resulting from Caspase-1-dependent GSDMD-N cleavage. AbstractEndothelial pyroptosis promotes cerebral ischemia/reperfusion injury (CIRI). Sodium Danshensu (SDSS) has been shown to attenuate CIRI and have anti-inflammatory properties in endothelial cells. However, the mechanism and effect of SDSS on alleviating endothelial pyroptosis after CIRI remains poorly understood. Thus, we aimed to investigate the efficacy and mechanism of SDSS in reducing endothelial pyroptosis. It has been shown that SDSS administration inhibited NLRP3 inflammasome-mediated pyroptosis. As demonstrated by protein microarrays, molecular docking, CETSA and ITDRFCETSA, SDSS bound strongly to CLIC4. Furthermore, SDSS can decrease its expression and inhibit its translocation. Its effectiveness was lowered by CLIC4 overexpression but not by knockdown. Overall The beneficial effect of SDSS against CI...
Source: BioFactors - Category: Biochemistry Authors: Tags: RESEARCH ARTICLE Source Type: research