Apaf-1 Pyroptosome Senses Mitochondrial Permeability Transition

Xu, Wanfeng; Che, Yuan; Zhang, Quan; Huang, Hai; Ding, Chujie; Wang, Yun; Wang, Guangji; Cao, Lijuan; Hao, Haiping

doi:10.1016/j.cmet.2020.11.018

Cited by 95 publications

(72 citation statements)

References 47 publications

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“…Cells were prepared as previously document [ 35 ]. 1 x 10 6 HCT-116 cells were fixed in 0.2 M phosphate buffer supplemented with 2.5% glutaraldehyde (G5882, Sigma-Aldrich) for 4 h. Cells were post-fixed for 60 min in 1% osmium tetroxide (75632, Sigma-Aldrich) and dehydrated in gradient ethanol solutions (15 min each step).…”

Section: Methodsmentioning

confidence: 99%

Network pharmacology for systematic understanding of Schisandrin B reduces the epithelial cells injury of colitis through regulating pyroptosis by AMPK/Nrf2/NLRP3 inflammasome

Zhang

Wang

Shen

et al. 2021

Aging

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Ulcerative colitis (UC) is a chronic inflammatory disease with increasing incidence and prevalence in many countries. The purpose of this study is to explore the function of Schisandrin B and its underlying molecular mechanisms in colitis. In this study, mice with colitis were induced by giving 2.0% dextran sulfate sodium (DSS, MP) in the drinking water for seven days. Furthermore, TCMSP server and GEO DataSets were used to analyze the mechanism of Schisandrin B in colitis. It was found that Schisandrin B presented colitis in mice model. At the same time, Schisandrin B not only reduced inflammation in vivo and vitro model of colitis, but also suppressed the nucleotide-binding oligomerization domain, leucine-rich repeat and pyrin domain-containing 3 (NLRP3) inflammasome in vivo and vitro model of colitis. In addition, Schisandrin B induced AMP-activated protein kinase (AMPK) / Nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway in model of colitis, and regulated AMPK protein at 316 sites. The inhibition of AMPK reduced the anti-inflammation effects of Schisandrin B on NLRP3 inflammasome. Apart from that, Schisandrin B decreased reactive oxygen species (ROS)-induced mitochondrial damage and reduced epithelial cells damage of colitis through regulating pyroptosis. Collectively, our novel findings for first time showed that, Schisandrin B suppressed NLRP3 inflammasome activation-mediated interleukin-1beta (IL-1β) level and pyroptosis in intestinal epithelial cells of colitis model through the activation of AMPK/Nrf2 dependent signaling-ROS-induced mitochondrial damage, which may be a significant therapeutic approach in the treatment of acute colitis.

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Section: Methodsmentioning

confidence: 99%

Network pharmacology for systematic understanding of Schisandrin B reduces the epithelial cells injury of colitis through regulating pyroptosis by AMPK/Nrf2/NLRP3 inflammasome

Zhang

Wang

Shen

et al. 2021

Aging

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“…Cristae density was calculated by using Image pro for area void of cristae as previously described [ 52 ]. Mitochondrial size was measured using tracing individual mitochondrion after calibration for distance (minimum of 40 mitochondria).…”

Section: Methodsmentioning

confidence: 99%

“…1x 10 5 /well of RAW264.7 cell was seeded into a 96-well plate and 100 μL JC-1 probe solution (C2006, Beyotime Biotechnology) was added into every well as previously described [ 52 ]. Absorbance was measured using a fluorescent reader (Synergy H1 Microplate Reader, Bio Tek, Winooski, USA).…”

Section: Methodsmentioning

confidence: 99%

“…1x 10 5 /well of RAW264.7 cell was seeded into a 96-well plate, diluted calcein-AM solution to 500 nM with solution buffer, incubated cells with for 20 min at 37° C, and added with 50 μL CoCl2 solution and incubated for 10 min. Absorbance was measured using the plate under Ex490/Em515 nm with fluorescent reader (Synergy H1 Microplate Reader, Bio Tek, Winooski, USA) as previously described [ 52 ].…”

Section: Methodsmentioning

confidence: 99%

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GPR43 regulation of mitochondrial damage to alleviate inflammatory reaction in sepsis

Zhang

Wang

et al. 2021

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Sepsis is a common critical illness in ICU and always a great difficulty in clinical treatment. GPR43 (G protein-coupled receptor 43) participates in regulating appetite and gastrointestinal peptide secretion to modulate fat decomposition and formation. However, the biological contribution of GPR43 on inflammation of sepsis has not been previously investigated. We investigated the mechanisms of GPR43 gene, which plays a possible role in distinguishing sepsis and contributes to the pathogenesis of sepsis-induced inflammatory reaction. Furthermore, we performed studies with mice induced to sepsis by Cecal Ligation and Puncture (CLP), Knockout GPR43 (GPR43-/-) mice, and Wild Type (WT) mice induced with CLP. In addition, lung tissues and cell samples were analyzed by histology, Quantitative Polymerase Chain Reaction (Q-PCR), Enzyme-linked Immunosorbent (ELISA) Assay, and western blot. GPR43 agonist could significantly reduce inflammation reactions and trigger lung injury in mice with sepsis. As for GPR43-/- mice, the risks of sepsis-induced inflammatory reactions and corresponding lung injury were promoted. On the one hand, the up-regulation of GPR43 gene reduced ROS mitochondrial damage to inhibit inflammatory reactions via the inactivation of NLRP3 Inflammasome by PPARγ/ Nox1/EBP50/ p47phox signal channel. On the other hand, the down-regulation of GPR43 promoted inflammatory reactions in vitro model through the acceleration of ROS-dependently mitochondrial damage by PPARγ/ Nox1/EBP50/ p47phox/ NLRP3 signal channel. These findings indicate that the inhibition of GPR43 as a possible important factor of sepsis may shed lights on the mechanism of sepsis-induced inflammation reaction.

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“…Pyroptosis is a novel pathway of PCD that occurs in parenchymal cells and nonparenchymal cells [ 29 , 30 , 31 ]. It is a form of PCD distinct from apoptosis.…”

Section: The Mechanism Of Pyroptosismentioning

confidence: 99%

Pyroptosis: Mechanisms and Links with Fibrosis

Song

Gong

Guo

2021

Cells

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Fibrosis is responsible for approximately 45% of deaths in the industrialized world and has been a major global healthcare burden. Excessive fibrosis is the primary cause of organ failure. However, there are currently no approved drugs available for the prevention or treatment of fibrosis-related diseases. It has become evident that fibrosis is characterized by inflammation. In a large number of studies of various organs in mice and humans, pyroptosis has been found to play a significant role in fibrosis. Pyroptosis is a form of programmed cell death mediated by the N-terminal fragment of cysteinyl aspartate-specific proteinase (caspase)-1-cleaved gasdermin D (GSDMD, producing GSDMD-N) that gives rise to inflammation via the release of some proinflammatory cytokines, including IL-1β, IL-18 and HMGB1. These cytokines can initiate the activation of fibroblasts. Inflammasomes, an important factor upstream of GSDMD, can activate caspase-1 to trigger the maturation of IL-1β and IL-18. Moreover, the inhibition of inflammasomes, proinflammatory cytokines and GSDMD can prevent the progression of fibrosis. This review summarizes the growing evidence indicating that pyroptosis triggers fibrosis, and highlights potential novel targets for antifibrotic therapies.

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Apaf-1 Pyroptosome Senses Mitochondrial Permeability Transition

Cited by 95 publications

References 47 publications

Network pharmacology for systematic understanding of Schisandrin B reduces the epithelial cells injury of colitis through regulating pyroptosis by AMPK/Nrf2/NLRP3 inflammasome

Network pharmacology for systematic understanding of Schisandrin B reduces the epithelial cells injury of colitis through regulating pyroptosis by AMPK/Nrf2/NLRP3 inflammasome

GPR43 regulation of mitochondrial damage to alleviate inflammatory reaction in sepsis

Pyroptosis: Mechanisms and Links with Fibrosis

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