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Abstract Title:

Magnesium protects against sepsis by blocking gasdermin D N-terminal-induced pyroptosis.

Abstract Source:

Cell Death Differ. 2019 Jun 17. Epub 2019 Jun 17. PMID: 31209359

Abstract Author(s):

Dingyu Wang, Jiashuo Zheng, Qiongyuan Hu, Cheng Zhao, Qianyue Chen, Peiliang Shi, Qin Chen, Yujie Zou, Dayuan Zou, Qiyao Liu, Jingwen Pei, Xiuwen Wu, Xiang Gao, Jianan Ren, Zhaoyu Lin

Article Affiliation:

Dingyu Wang

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.

Study Type : Animal Study
Additional Links
Pharmacological Actions : Cytoprotective : CK(190) : AC(94)

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Sayer Ji
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