Effect of genetic deletion of Gsdmd on mice fed an oxalate rich-diet
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PROVIDER: PRJNA1175545 | ENA |
REPOSITORIES: ENA
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Project description:The role of pyroptosis, an inflammatory form of cell death involving the formation of Gasdermin-D (GSDMD) pores, in chronic oxalate nephropathy remains unknown. We report genetic deletion of Gsdmd exacerbated oxalate nephropathy in mice in association with accelerated necroptosis.Our transcriptional analysis using kidneys from mice fed an oxalate-rich diet or control diet revealed significant changes in the gene sets related to leukocyte migration, chemokine pathways, mitochondrial dysfunction, and complement pathways between Gsdmd KO and WT mice. These differences may be attributed to variations in the substances released during cell death.
2025-04-01 | GSE279923 | GEO
Project description:Gasdermin D (GSDMD) is the executioner of pyroptosis, which is important for host defense against pathogen infection. After activation, caspase-mediated cleavage of GSDMD liberates an N-terminal fragment (GSDMD-NT), which oligomerizes and forms pores in the plasma membrane, leading to cell death and subsequent release of proinflammatory cytokines. How this process is spatiotemporally controlled to promote pyroptosis in cells has been a fundamental, unaddressed question. Here, we identify GSDMD as a substrate for reversible S-palmitoylation on cysteine 192 (Cys192) in response to lipopolysaccharide (LPS) stimulation. We found that the palmitoyl acyltransferase DHHC7palmitoylates GSDMD to direct its cleavage by caspases in pyroptosis by promoting the interaction of GSDMD and caspases. We further show that after GSDMD cleavage, palmitoylation of GSDMD-NTpromotes its plasma membrane translocation and binding, and then acyl protein thioesterase 2 (APT2) depalmitoylates GSDMD-NT to unmask the Cys192 residue to promote oxidation-mediated oligomerization and pyroptosis. Perturbation of either palmitoylation or depalmitoylation suppresses pyroptosis, extends the survival of mice from LPS-induced lethal septic shock and sensitizes mice to bacterial infection. Thus. our findings reveal a model through which a palmitoylation-depalmitoylationrelay spatially and temporally controls GSDMD activation in pyroptosis.
2024-02-25 | GSE252911 | GEO
Project description:Gasdermin D (GSDMD) is the executioner of pyroptosis, which is important for host defense against pathogen infection. After activation, caspase-mediated cleavage of GSDMD liberates an N-terminal fragment (GSDMD-NT), which oligomerizes and forms pores in the plasma membrane, leading to cell death and subsequent release of proinflammatory cytokines. How this process is spatiotemporally controlled to promote pyroptosis in cells has been a fundamental, unaddressed question. Here, we identify GSDMD as a substrate for reversible S-palmitoylation on cysteine 192 (Cys192) in response to lipopolysaccharide (LPS) stimulation. We found that the palmitoyl acyltransferase DHHC7palmitoylates GSDMD to direct its cleavage by caspases in pyroptosis by promoting the interaction of GSDMD and caspases. We further show that after GSDMD cleavage, palmitoylation of GSDMD-NTpromotes its plasma membrane translocation and binding, and then acyl protein thioesterase 2 (APT2) depalmitoylates GSDMD-NT to unmask the Cys192 residue to promote oxidation-mediated oligomerization and pyroptosis. Perturbation of either palmitoylation or depalmitoylation suppresses pyroptosis, extends the survival of mice from LPS-induced lethal septic shock and sensitizes mice to bacterial infection. Thus. our findings reveal a model through which a palmitoylation-depalmitoylationrelay spatially and temporally controls GSDMD activation in pyroptosis.
2024-02-25 | GSE252893 | GEO
Project description:The composition of the diet affects many processes in the body, including body weight and endocrine system. We have previously shown that dietary fat also affects the immune system. Mice fed high fat diet rich in polyunsaturated fatty acids survive S. aureus infection to a much greater extent than mice fed high fat diet rich in saturated fatty acids. Here we present data regarding the dietary effects on protein expression in spleen from mice fed three different diets, I) low fat/chow diet (LFD, n=4), II) high fat diet rich in saturated fatty acids (HFD-S, n=4) and III) high fat diet rich in polyunsaturated fatty acids (HFD-P, n=4). We performed mass spectrophotometry based quantitative proteomics analysis of isolated spleen by implementing the isobaric tags for relative and absolute quantification (iTRAQ) approach. Mass spectrometry data were analysed using Proteome Discoverer 2.4 software using the search engine mascot against Mus musculus in SwissProt. 924 proteins are identified in all sets (n=4) for different dietary effects taken for statistical analysis using Qlucore Omics Explorer software. Only 20 proteins were found to be differentially expressed with a cut-off value of false discovery rate < 0.1 (q-value) when comparing HFD-S and HFD-P but no differentially expressed proteins were found when LFD was compared with HFD-P or HFD-S. We identified a subset of proteins that showed an inverse expression pattern between two high fat diets. These differentially expressed proteins were further classified by gene ontology for their role in biological processes and molecular functions.
2020-08-06 | PXD020365 | Pride
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2020-07-06 | GSE137827 | GEO
Project description:Mouse Iron Distribution Dynamics
Dynamic model of iron distribution in mice. This model includes only normal iron with the parameters that fit the data from Lopes et al. 2010 for mice fed a rich iron diet.
This model does not include the radioiron tracer species. It is appropriate to study the properties in conditions where no tracers are used (for example for steady state analysis).
2024-09-02 | BIOMD0000000738 | BioModels
Project description:Metabolic dysfunction-associated steatohepatitis (MASH) is on the rise, and with limited pharmacological therapy available, identification of new metabolic targets is urgently needed. Oxalate is a terminal metabolite produced from glyoxylate by lactate dehydrogenase (LDHA). The liver-specific alanine-glyoxylate aminotransferase (AGXT) detoxifies glyoxylate, preventing oxalate accumulation. We report that AGXT is suppressed and LDHA is activated in livers from patients and mice with MASH, leading to oxalate overproduction. In turn, oxalate promotes steatosis in hepatocytes by inhibiting peroxisome proliferator activated receptor-alpha (PPARα) transcription and fatty acid β-oxidation (FAO), and induces monocyte chemotaxis via C-C motif chemokine ligand 2. In male mice with diet-induced MASH, blocking oxalate overproduction through hepatocyte-specific AGXT overexpression or pharmacological inhibition of LDHA potently lower steatosis, inflammation, and fibrosis by inducing PPARα-driven FAO, and suppressing monocyte chemotaxis, nuclear factor-kappaB and transforming growth factor-beta targets. These findings highlight hepatic oxalate overproduction as a new target for the treatment of MASH.
2024-08-07 | GSE265985 | GEO
Project description:We identified that GSDMD was required for the pathogenesis of EAE, and GSDMD deficiency in peripheral myeloid cells impaired the infiltration of immune cells into the CNS , leading to the suppression of neuroinflammation and demyelination.The purpose of this experiment was to identify how GSDMD induces EAE.
2019-08-22 | GSE126289 | GEO
Project description:parental HEK293T were challenged with 1064 µg/cm2 calcium oxalate monohydrate (COM) or sodium oxalate (NaOx) 4mM or vehicle for 24 hours and DNA microarray was performed. We observed and selected two-fold upregulation of laminin, beta 3 (LAMB3), early growth response 1 (EGR1), gremlin 1, DAN family BMP antagonist, Ca++-dependent secretion activator 2, Ras association domain family member 3, interleukin 33 and bone morphogenetic protein 8a , and two-fold down-regulation of interleukin 37 and intercellular adhesion molecule 1 in COM lord compared to vhicle.
2021-10-29 | GSE186676 | GEO
Project description:Specific pathogen free wild-type C57Bl/6 male mice fed ketogenic diet (Bio-Serv AIN-76-A) for 4 weeks Keywords: RNA Expression Array Hearts from 12 week-old mice that were maintained on a standard polysacchardide-rich chow until the age of 8 weeks, at which time they were switched to a ketogenic diet (ad libitum) and maintained for 4 additional weeks prior to collection of tissues
2010-06-16 | E-GEOD-21368 | biostudies-arrayexpress