{"id":"fadf4e8d-cf53-5643-b47f-b3d358560e58","stable_key":"a8bedee0-a740-5bbb-921e-bfd144c7b68c:astaxanthin-nrf2-loss","predicate":"knockdown_blunts","statement":"Nrf2 siRNA reduced astaxanthin-induced HO-1 expression by about 60% in HUVECs.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"bec4c404-203f-5fa9-ba8c-29f7297c2580","mechanism_event_label":"The response was weaker when its transcriptional machinery was reduced.","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":"bec4c404-203f-5fa9-ba8c-29f7297c2580","stable_key":"a8bedee0-a740-5bbb-921e-bfd144c7b68c:astaxanthin-nrf2-loss-event","event_type":"observed_relationship","label":"The response was weaker when its transcriptional machinery was reduced.","description":"Nrf2 siRNA reduced astaxanthin-induced HO-1 expression by about 60% in HUVECs.","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":"1bf8b9c0-9c38-5c8a-b5da-f00b0eeca36f","slug":"astaxanthin","display_name":"Astaxanthin","entity_type_key":"small_molecule"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""}]},"contexts":[{"dimension":"availability_state","value_text":"machinery_impairment","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null},{"dimension":"evidence_access","value_text":"Primary abstract","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Human endothelial-cell Nrf2 knockdown.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Partial suppression does not identify all upstream sensors or show that more astaxanthin can replace Nrf2.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Astaxanthin collection; molecular form, preparation, species, exposure and manipulation remain explicit.","comparator":null,"unit":null,"notes":"","entity":{"slug":"astaxanthin","display_name":"Astaxanthin","entity_type_key":"small_molecule"}},{"dimension":"plain_language","value_text":"The response was weaker when its transcriptional machinery was reduced.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"Astaxanthin Induces the Nrf2/HO-1 Antioxidant Pathway in Human Umbilical Vein Endothelial Cells by Generating Trace Amounts of ROS. · 2018 · https://pubmed.ncbi.nlm.nih.gov/29381356/ · DOI 10.1021/acs.jafc.7b05493","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"trigger_kind","value_text":"machinery_impairment","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null}],"evidence":[{"id":"28027c78-48b2-538e-9280-5deb38ee6128","evidence_kind":"source_excerpt","locator":"Lines 230-236","start_line":230,"end_line":236,"excerpt":"## astaxanthin-nrf2-loss\nThe response was weaker when its transcriptional machinery was reduced.\nNrf2 siRNA reduced astaxanthin-induced HO-1 expression by about 60% in HUVECs.\nModel: Human endothelial-cell Nrf2 knockdown.\nLimitations: Partial suppression does not identify all upstream sensors or show that more astaxanthin can replace Nrf2.\nEvidence access: Primary abstract\nAstaxanthin Induces the Nrf2/HO-1 Antioxidant Pathway in Human Umbilical Vein Endothelial Cells by Generating Trace Amounts of ROS. · 2018 · https://pubmed.ncbi.nlm.nih.gov/29381356/ · DOI 10.1021/acs.jafc.7b05493","model_system":"Human endothelial-cell Nrf2 knockdown.","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":"4fd91ea6-78b4-5bfe-93e3-686fbef9f678","stable_key":"import-a8bedee0-a740-5bbb-921e-bfd144c7b68c","title":"Astaxanthin: transport, membrane chemistry, signaling and nutrient interactions (2026-09-19)","document_type":"imported_text","citation_label":"AI-assisted research curation; primary-abstract references and experimental limitations individually identified. 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