Magnesium protects against sepsis by blocking gasdermin D N-terminal-induced pyroptosis.
Wang D , Zheng J , Hu Q , Zhao C , Chen Q , Shi P , Chen Q , Zou Y , Zou D , Liu Q , Pei J , Wu X , Gao X , Ren J , Lin Z 
Cell Death Differ.2019 Jun 17 ; ():.
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Hypomagnesemia is a significant risk factor for critically ill patients to develop sepsis, a life-threatening disease with a mortality rate over 25%. Our clinic data analysis showed that hypomagnesemia is associated with a decreased monocyte count in septic patients. At the cellular level, we found that Mg inhibits pyroptosis. Specifically, Mg limits the oligomerization and membrane localization of gasdermin D N-terminal (GSDMD-NT) upon the activation of either the canonical or noncanonical pyroptotic pathway. Mechanistically, we demonstrated that Ca influx is a prerequisite for the function of GSDMD-NT. Mg blocks Ca influx by inhibiting the ATP-gated Ca channel P2X7, thereby impeding the function of GSDMD-NT and inhibiting lipopolysaccharide (LPS)-induced noncanonical pyroptosis. Furthermore, Mg administration protects mice from LPS-induced lethal septic shock. Together, our data reveal the underlying mechanism of how Mg inhibits pyroptosis and suggest potential clinic applications of magnesium supplementation for sepsis prevention and treatment.
PMID: 31209359 [PubMed - as supplied by publisher]
PMID: 31209359 [PubMed - as supplied by publisher]
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