PMID:
Cell Death Differ. 2019 Jun 17. Epub 2019 Jun 17. PMID: 31209359
Abstract Title:
Magnesium protects against sepsis by blocking gasdermin D N-terminal-induced pyroptosis.
Abstract:
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 Mginhibits pyroptosis. Specifically, Mglimits 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 Cainflux is a prerequisite for the function of GSDMD-NT. Mgblocks Cainflux by inhibiting the ATP-gated Cachannel P2X7, thereby impeding the function of GSDMD-NT and inhibiting lipopolysaccharide (LPS)-induced noncanonical pyroptosis. Furthermore, Mgadministration protects mice from LPS-induced lethal septic shock. Together, our data reveal the underlying mechanism of how Mginhibits pyroptosis and suggest potential clinic applications of magnesium supplementation for sepsis prevention and treatment.
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