{"id":"289f1adc-194d-5e37-b8fa-5a30d6a8a96c","stable_key":"e13b03e1-a614-543a-ac1b-97df18cfe30d:iron-cystine-ferroptosis","predicate":"inhibits","statement":"Erastin inhibited cystine uptake through system xc-minus, weakening antioxidant defenses before iron-dependent oxidative death.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"90c35ec1-c251-5f99-b918-4be802cd7eba","mechanism_event_label":"The death pathway connected iron with the supply of material needed for glutathione.","subject":{"id":"b5dcb638-5d9d-5506-b6e4-f35a6676eb78","slug":"erastin","display_name":"Erastin","entity_type_key":"small_molecule"},"object":{"id":"609df3aa-110e-54b4-b072-985dc72c81b2","slug":"cystine-uptake","display_name":"cystine uptake","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"90c35ec1-c251-5f99-b918-4be802cd7eba","stable_key":"e13b03e1-a614-543a-ac1b-97df18cfe30d:iron-cystine-ferroptosis-event","event_type":"biochemical_relationship","label":"The death pathway connected iron with the supply of material needed for glutathione.","description":"Erastin inhibited cystine uptake through system xc-minus, weakening antioxidant defenses before iron-dependent oxidative death.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"85ca0bb8-8a67-59fe-8334-e0f6617380b7","slug":"ferroptosis","display_name":"Ferroptosis","entity_type_key":"cellular_process"},"role":"downstream_outcome","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"b5dcb638-5d9d-5506-b6e4-f35a6676eb78","slug":"erastin","display_name":"Erastin","entity_type_key":"small_molecule"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"609df3aa-110e-54b4-b072-985dc72c81b2","slug":"cystine-uptake","display_name":"cystine uptake","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""}]},"contexts":[{"dimension":"evidence_span","value_text":"{\"source_cache\": \"artifacts/iron-research/22632970.abstract.txt\", \"locator\": \"Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"c0137d17ae5942c8904ece05ab6513f4fad588149ed0d7167e49f01a63b36cb0\", \"start_char\": 0, \"end_char\": 1089, \"text_sha256\": \"c0137d17ae5942c8904ece05ab6513f4fad588149ed0d7167e49f01a63b36cb0\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Chemical and genetic characterization of nonapoptotic cell death","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Erastin and ferrostatin-1 experiments","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Experimental ferroptosis; dietary iron is not equated with a cancer-cell-death drug exposure.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Iron research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"iron","display_name":"Iron","entity_type_key":"nutrient_element"}},{"dimension":"organism","value_text":"Cancer-cell systems and rat brain slices","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"The death pathway connected iron with the supply of material needed for glutathione.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[iron-p22632970] Ferroptosis: an iron-dependent form of nonapoptotic cell death. (2012). https://pubmed.ncbi.nlm.nih.gov/22632970/ DOI: 10.1016/j.cell.2012.03.042","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Cellular iron, cystine transport and oxidative injury","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"da0fffd1-8f10-5719-8ae9-c9284bcce996","evidence_kind":"source_excerpt","locator":"Lines 1239-1250","start_line":1239,"end_line":1250,"excerpt":"### iron-cystine-ferroptosis\nErastin inhibited cystine uptake through system xc-minus, weakening antioxidant defenses before iron-dependent oxidative death.\nCondition category: normal\nnutrient_topic: Iron research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: The death pathway connected iron with the supply of material needed for glutathione.\norganism: Cancer-cell systems and rat brain slices\ntissue_or_cell_type: Cellular iron, cystine transport and oxidative injury\nexperimental_model: Chemical and genetic characterization of nonapoptotic cell death\nlimitations: Experimental ferroptosis; dietary iron is not equated with a cancer-cell-death drug exposure.\nexposure: Erastin and ferrostatin-1 experiments\nevidence_span: {\"source_cache\": \"artifacts/iron-research/22632970.abstract.txt\", \"locator\": \"Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"c0137d17ae5942c8904ece05ab6513f4fad588149ed0d7167e49f01a63b36cb0\", \"start_char\": 0, \"end_char\": 1089, \"text_sha256\": \"c0137d17ae5942c8904ece05ab6513f4fad588149ed0d7167e49f01a63b36cb0\"}\n[iron-p22632970] Ferroptosis: an iron-dependent form of nonapoptotic cell death. 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