Fig. 7: Schematic diagram depicting the proposed IP3R2-mediated Ca2+ signals in cardiomyocyte pyroptosis induced by LPS. | Cell Death Discovery

Fig. 7: Schematic diagram depicting the proposed IP3R2-mediated Ca2+ signals in cardiomyocyte pyroptosis induced by LPS.

From: IP3R2-mediated Ca2+ release promotes LPS-induced cardiomyocyte pyroptosis via the activation of NLRP3/Caspase-1/GSDMD pathway

Fig. 7

LPS stimulation induces IP3R2 upregulation in NRCMs. Then, IP3R2-mediated Ca2+ release participates in LPS induced-cardiomyocytes pyroptosis. NLRP3 inflammasome is activated by IP3R-mediated Ca2+ release, characterized by upregulated NLRP3 expression. The activation of NLRP3 inflammasome governs the cleavage and activation of pro-Caspase-1. Activated Caspase-1 cleaves the full-length gasdermin D (GSDMD-FL) protein to release the N-terminal of GSDMD (GSDMD-NT), which results in GSDMD pore formation. Meanwhile, mature IL-18 and IL-1β are cleaved by the activated NLRP3/Caspase-1 pathway, and the cleaved IL-18 and IL-1β are released through the GSDMD pore in the cell membrane and induces pyroptosis. It is worth mentioning that the mutual regulation of IP3R2 and ER stress further exacerbates the pyroptosis process. Thus, inhibiting IP3R2 could be a promising strategy for the prevention of SIC.

Back to article page