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

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

doi:10.1038/s41418-019-0366-x

Cited by 78 publications

(57 citation statements)

References 41 publications

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“…44 A recent study showed that Mg 2+ at high concentrations (5-20 mM) inhibited pyroptosis by limiting the localization of GSDMD p30 to the plasma membrane. 47 This study also suggested that the membrane localization of GSDMD p30 required the influx of Ca 2+ , which is affected by high Mg 2+ . The discrepancies in these findings may be The transcription factors IRF1 and IRF2 transactivate the Gsdmd gene.…”

Section: Regulation Of Pyroptosismentioning

confidence: 62%

“…Broz and colleagues demonstrated that the ESCRT‐III complex is recruited to the plasma membrane during pyroptosis and suggested that the ESCRT machinery negatively regulates pyroptosis 44 . A recent study showed that Mg 2+ at high concentrations (5–20 m m ) inhibited pyroptosis by limiting the localization of GSDMD p30 to the plasma membrane 47 . This study also suggested that the membrane localization of GSDMD p30 required the influx of Ca 2+ , which is affected by high Mg 2+ .…”

Section: Pyroptosismentioning

confidence: 94%

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Inflammasome‐associated cell death: Pyroptosis, apoptosis, and physiological implications

Tsuchiya

2020

Microbiology and Immunology

166

144

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Section: Regulation Of Pyroptosismentioning

confidence: 62%

Section: Pyroptosismentioning

confidence: 94%

Inflammasome‐associated cell death: Pyroptosis, apoptosis, and physiological implications

Tsuchiya

2020

Microbiology and Immunology

166

144

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“…Wang et al showed that low Mg level is associated with decreased monocyte cell count in patients with sepsis, Mg supplementation protects mice from LPS-induced septic shock. 27 Salem et al 28 claimed that Mg deficiency could lead to adverse outcomes of endotoxin attacks, and replacement therapy may be necessary in the case of Mg deficiency. Second, Mg promotes renal vasodilation through competing for calcium transport system, releasing nitric oxide (NO).…”

Section: Discussionmentioning

confidence: 99%

<p>The Effect of Admission Serum Magnesium on the Acute Kidney Injury Among Patients with Malignancy</p>

Shen¹,

Wang²,

Xu³

et al. 2020

CMAR

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This study aimed to explore the relationship between serum magnesium (Mg) levels and incidence of acute kidney injury (AKI) in patients with malignancy. Patients and Methods: Hospitalized patients with malignancy between October 1, 2014 and September 30, 2015 in Zhongshan Hospital were recruited. All relevant data were extracted from the electronic database. Results: All 99,845 patients were enrolled and 16,082 eligible patients were divided into three groups according to admission serum Mg levels in this study. Among them, 2383 (14.8%) cases were diagnosed as AKI. The incidence of AKI showed a V trend with the increase of serum Mg level. The effect of low serum Mg level on the onset of AKI seems to be greater than high serum Mg level. Patients with low serum Mg level spent a longer time in the hospital than those with normal serum Mg level and high serum Mg level. Further, multivariate logistic regression model was used to assess the importance of serum Mg level to influence AKI incidence. There was a higher AKI incidence in patients with magnesium level 0.66mmol/L or less (aOR=2.438, 95% CI=1.696, 3.505). Conclusion: Low serum Mg level might be a independent risk factor for AKI in patients with malignancy. Appropriate clinical intervention for serum Mg disorder may contribute to decreasing the incidence of AKI and the possibility of poor outcomes in cancer patients.

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“…Previous studies have demonstrated that the suppression of GSDMD-NT-induced pyroptosis offers therapeutic effects in sepsis treatment. 28 , 29 Caspase-1 activation is a typical marker of canonical inflammasome activation, while caspase-11 activation is a marker of non-canonical inflammasome activation. 21 , 30 In the non-canonical pyroptosis pathway, GSDMD-NT and caspase-11 activate the NLRP3 inflammasome and recruit ASC to induce the maturation and release of IL-1β and IL-18.…”

Section: Discussionmentioning

confidence: 99%

Roles of the pyroptosis signaling pathway in a sepsis-associated encephalopathy cell model

et al. 2020

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Objectives The inhibition of pyroptosis has a protective effect in sepsis-associated encephalopathy (SAE). However, the mechanisms underlying pyroptosis in SAE remain to be elucidated. Methods Here, we investigated the effects of the caspase inhibitors, Belnacasan (Beln) and Wedelolactone (Wede), on an induced model of SAE in P12 cells, using immunofluorescence, ELISA, western blotting, and flow cytometry. Results The cell viability decreased, IL-1β and IL-18 secretion increased, and the levels of the caspase cleavage products, N-terminal gasdermin D, cleaved caspase-1, and cleaved caspase-11, increased in P12 cells following combined treatment with lipopolysaccharides (LPS) and adenosine triphosphate (ATP). However, treatment with Beln or Wede ameliorated the effects induced by LPS and ATP. Neither Beln nor Wede notably affected the levels of cell apoptosis-associated proteins but these inhibitors regulated the levels of cell pyroptosis-associated proteins. Further, the combination of Beln and Wede exerted greater inhibitory effects on cell pyroptosis than either Beln or Wede alone. Conclusions The results demonstrated that both the canonical and non-canonical signaling pathways of cell pyroptosis are involved in LPS-induced cell damage and that the non-canonical signaling pathway may be involved to a greater extent. This suggests that the inhibition of pyroptosis may exert potential therapeutic effects on SAE.

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

Cited by 78 publications

References 41 publications

Inflammasome‐associated cell death: Pyroptosis, apoptosis, and physiological implications

Inflammasome‐associated cell death: Pyroptosis, apoptosis, and physiological implications

<p>The Effect of Admission Serum Magnesium on the Acute Kidney Injury Among Patients with Malignancy</p>

Roles of the pyroptosis signaling pathway in a sepsis-associated encephalopathy cell model

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