{"id":"b2031346-d480-5610-85df-77c0e047fe77","stable_key":"research:caspase-gsdmd","predicate":"cleave_to_produce","statement":"Inflammatory caspase activation cleaves GSDMD to produce its cytotoxic N-terminal fragment in the inspected pyroptosis pathway.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"literature_reviewed:direct_experimental","direction":"positive","is_public":true,"mechanism_event_id":"01ea9fd7-c84d-5fcf-920c-de7993155551","mechanism_event_label":"Caspases cut gasdermin before its execution fragment acts.","subject":{"id":"586db8c7-1900-58a3-ae13-bc52de3c1424","slug":"inflammatory-caspases","display_name":"inflammatory caspases","entity_type_key":"protein_family"},"object":{"id":"4306e8e4-2459-52dc-854a-33a4df851985","slug":"gsdmd-n","display_name":"cleaved GSDMD N-terminal fragment","entity_type_key":"protein_state"},"evidence_count":1,"mechanism_event":{"id":"01ea9fd7-c84d-5fcf-920c-de7993155551","stable_key":"research:caspase-gsdmd","event_type":"proteolysis","label":"Caspases cut gasdermin before its execution fragment acts.","description":"Inflammatory caspase activation cleaves GSDMD to produce its cytotoxic N-terminal fragment in the inspected pyroptosis pathway.","status":"active","compartment":null,"participants":[{"entity":{"id":"a29f5438-78e3-5f8e-b037-94316ef8ecb4","slug":"gsdmd","display_name":"GSDMD","entity_type_key":"protein"},"role":"substrate","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"586db8c7-1900-58a3-ae13-bc52de3c1424","slug":"inflammatory-caspases","display_name":"inflammatory caspases","entity_type_key":"protein_family"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"4306e8e4-2459-52dc-854a-33a4df851985","slug":"gsdmd-n","display_name":"cleaved GSDMD N-terminal fragment","entity_type_key":"protein_state"},"role":"object","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""}]},"contexts":[{"dimension":"cell_type","value_text":"Macrophages","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Myeloid Gpx4 models, macrophage cytosolic LPS/E. coli and mouse sepsis","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Not a demonstrated complete human dietary-deficiency sequence.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"organism","value_text":"Mus musculus","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"2bae7807-d467-5fc1-82df-dae97e9f8a73","evidence_kind":"curated_literature_summary","locator":"lines 1384-1394","start_line":1384,"end_line":1394,"excerpt":"## caspase-gsdmd\n\nCaspases cut gasdermin before its execution fragment acts.\n\nInflammatory caspase activation cleaves GSDMD to produce its cytotoxic N-terminal fragment in the inspected pyroptosis pathway.\n\nOrganism: Mus musculus\nCell type: Macrophages\nExperimental model: Myeloid Gpx4 models, macrophage cytosolic LPS/E. coli and mouse sepsis\nLimitations: Not a demonstrated complete human dietary-deficiency sequence.\nPrimary reference: [Lipid peroxidation drives gasdermin D-mediated pyroptosis in lethal polymicrobial sepsis](https://pmc.ncbi.nlm.nih.gov/articles/PMC6043361/)","model_system":"Myeloid Gpx4 models, macrophage cytosolic LPS/E. coli and mouse sepsis","directness":"author_interpretation","verification_status":"secondary_verified","notes":"Curated summary; inspect the linked primary papers for original methods and results.","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"4f892f13-06ea-5199-a33c-a703f35c80ae","stable_key":"selenium-research-2026-09-17","title":"Selenium: literature corrections and mechanism additions","document_type":"curated_literature_review","citation_label":"Metabolic Ledger literature curation, 17 September 2026; primary papers linked individually","file_path":"","sha256":"0b818b10c1c7120e5caf7f4d4019d7bd025d745692e424f515d3ef903c9ab7f3","revision_id":"80984e03-5f0f-5877-8094-afef7637444e","review_status":"secondary_verified","notes":"Secondary curated summaries of primary experiments, with explicit models and limitations. Not archived primary full text."}}],"relations":[],"conflicts":[],"corrections":[{"id":"c5fd7563-7a73-5a53-887a-08e843f90af3","title":"GSDMD cleavage precedes the inspected PLCG1/calcium execution phase","kind":"contradiction","status":"corrected","why":"The source puts PLCG1/calcium before cleavage; inspected experiments test it downstream of GSDMD-N.","resolution":"Include inflammatory-caspase cleavage and preserve stimulus/model limits.","created_at":"2026-09-17 07:19:34","record_type":"correction","display_label":"Correction history","record_url":"/corrections/c5fd7563-7a73-5a53-887a-08e843f90af3","literature_review":{"revision_id":"80984e03-5f0f-5877-8094-afef7637444e","start_line":1654,"end_line":1659,"papers":[{"paper_key":"kang-2018","title":"Lipid peroxidation drives gasdermin D-mediated pyroptosis in lethal polymicrobial sepsis","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC6043361/","doi":"10.1016/j.chom.2018.05.009","year":2018,"model":"Myeloid Gpx4 models, macrophage cytosolic LPS/E. coli and mouse sepsis","summary":"GSDMD cleavage precedes the GSDMD-N execution phase involving PLCG1/calcium."}]},"sides":[{"conflict_id":"c5fd7563-7a73-5a53-887a-08e843f90af3","ordinal":0,"label":"Original preserved statement","revision_id":"fbed30e0-1c0d-5b83-8a1f-2867fbe8a5b5","start_line":250,"end_line":250,"quote":"**Second, independent route:** GPX4 in macrophages restrains LPS-driven sepsis. GPX4 loss → membrane lipid peroxidation → PLCγ1 activation → Ca²⁺ → **GSDMD cleavage → pyroptosis.** Ferroptotic chemistry feeding a pyroptotic execution.","claim_id":null,"source_key":"immune","source_title":"Selenium in immune cells","claim_ids":[]},{"conflict_id":"c5fd7563-7a73-5a53-887a-08e843f90af3","ordinal":1,"label":"Literature correction and experimental limits","revision_id":"80984e03-5f0f-5877-8094-afef7637444e","start_line":1654,"end_line":1659,"quote":"## GSDMD cleavage precedes the inspected PLCG1/calcium execution phase\n\nThe source puts PLCG1/calcium before cleavage; inspected experiments test it downstream of GSDMD-N.\n\nInclude inflammatory-caspase cleavage and preserve stimulus/model limits.\nPrimary reference: [Lipid peroxidation drives gasdermin D-mediated pyroptosis in lethal polymicrobial sepsis](https://pmc.ncbi.nlm.nih.gov/articles/PMC6043361/)","claim_id":null,"source_key":"selenium-research-2026-09-17","source_title":"Selenium: literature corrections and mechanism additions","claim_ids":[]}]}],"research":{"topic":"Selenium scientific audit","plain_language":"Caspases cut gasdermin before its execution fragment acts.","evidence_scope":"direct_experimental","papers":[{"key":"kang-2018","title":"Lipid peroxidation drives gasdermin D-mediated pyroptosis in lethal polymicrobial sepsis","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC6043361/","doi":"10.1016/j.chom.2018.05.009","year":2018,"model":"Myeloid Gpx4 models, macrophage cytosolic LPS/E. coli and mouse sepsis","summary":"GSDMD cleavage precedes the GSDMD-N execution phase involving PLCG1/calcium."}]}}