{"id":"66ac95a7-7361-527e-916f-8e463866a2db","stable_key":"88eb7407-f147-558b-889b-0c89c4e0aa4a:spermidine-hmox1-iron","predicate":"promotes_hmox1_response","statement":"The study linked elevated NRF2 to HMOX1 upregulation and increased labile ferrous iron during combination treatment.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"01d465ae-c093-5f3b-84f1-9c5b8c04b209","mechanism_event_label":"Heme breakdown links this response to iron availability.","subject":{"id":"dc472dd3-d383-567a-ab37-a9ec4e112df4","slug":"nfe2l2","display_name":"Human Nrf2 / NFE2L2","entity_type_key":"protein"},"object":{"id":"26298c7c-5265-5bf5-a435-e0fa98a3ac10","slug":"hmox1","display_name":"Human heme oxygenase 1 / HMOX1","entity_type_key":"protein"},"evidence_count":1,"mechanism_event":{"id":"01d465ae-c093-5f3b-84f1-9c5b8c04b209","stable_key":"88eb7407-f147-558b-889b-0c89c4e0aa4a:spermidine-hmox1-iron-event","event_type":"observed_relationship","label":"Heme breakdown links this response to iron availability.","description":"The study linked elevated NRF2 to HMOX1 upregulation and increased labile ferrous iron during combination treatment.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"dc472dd3-d383-567a-ab37-a9ec4e112df4","slug":"nfe2l2","display_name":"Human Nrf2 / NFE2L2","entity_type_key":"protein"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"26298c7c-5265-5bf5-a435-e0fa98a3ac10","slug":"hmox1","display_name":"Human heme oxygenase 1 / HMOX1","entity_type_key":"protein"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"7014993c-468f-5c6b-ab04-80c87f9dfd9f","slug":"spermidine","display_name":"Spermidine","entity_type_key":"small_molecule"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"59d6d1cd-df32-5b58-b950-3188bc7b95d6","slug":"iron-ii","display_name":"Ferrous iron","entity_type_key":"ion"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""},{"entity":{"id":"b5dcb638-5d9d-5506-b6e4-f35a6676eb78","slug":"erastin","display_name":"Erastin","entity_type_key":"small_molecule"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":4,"notes":""}]},"contexts":[{"dimension":"evidence_access","value_text":"Primary full text","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Human prostate cancer combination-treatment model.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"NRF2/HMOX1 direction depends on cell state and iron handling; no universal ferroptosis prediction.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Spermidine collection; molecular form, preparation, species, exposure and manipulation remain explicit.","comparator":null,"unit":null,"notes":"","entity":{"slug":"spermidine","display_name":"Spermidine","entity_type_key":"small_molecule"}},{"dimension":"plain_language","value_text":"Heme breakdown links this response to iron availability.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"Spermidine inactivates proteasome activity and enhances ferroptosis in prostate cancer. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40486852/ · DOI 10.1016/j.apsb.2025.02.023","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"27d065ef-288e-5775-9a0e-6afdcdf1ab2b","evidence_kind":"source_excerpt","locator":"Lines 526-532","start_line":526,"end_line":532,"excerpt":"## spermidine-hmox1-iron\nHeme breakdown links this response to iron availability.\nThe study linked elevated NRF2 to HMOX1 upregulation and increased labile ferrous iron during combination treatment.\nModel: Human prostate cancer combination-treatment model.\nLimitations: NRF2/HMOX1 direction depends on cell state and iron handling; no universal ferroptosis prediction.\nEvidence access: Primary full text\nSpermidine inactivates proteasome activity and enhances ferroptosis in prostate cancer. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40486852/ · DOI 10.1016/j.apsb.2025.02.023","model_system":"Human prostate cancer combination-treatment model.","directness":"reported_statement","verification_status":"source_derived_draft","notes":"Original curation paraphrase; evidence access and experimental limitations specified.","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"4348f3f8-0180-58a3-b61c-55d03bb322d2","stable_key":"import-88eb7407-f147-558b-889b-0c89c4e0aa4a","title":"Spermidine: biosynthesis, hypusination, transport and cross-nutrient mechanisms (2026-09-19)","document_type":"imported_text","citation_label":"AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text.","file_path":"","sha256":"8eec8784bc2bd0384cfd53c6603c4ced8e53c227d9ab29ed85594c43e34c68ef","revision_id":"7c421a18-4526-59f6-b84e-4be533bc35ac","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}