{"id":"d04ab706-3d4a-589a-9d9f-bb3c7858ca26","stable_key":"59b18080-c560-563d-abc5-bac4ee82a27c:ergothioneine-endothelial-entry-loss","predicate":"silencing_removes_protection","statement":"SLC22A4 siRNA reduced ergothioneine uptake and abolished its cytoprotection in human brain microvascular endothelial cells.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"8df1dd06-9e0b-510c-8f83-a65757a43068","mechanism_event_label":"Protection depended on getting the compound inside.","subject":{"id":"1509c925-fc5e-5a36-aa59-96bcc489965a","slug":"slc22a4","display_name":"Human ergothioneine transporter OCTN1 / SLC22A4","entity_type_key":"protein"},"object":{"id":"bf762512-ad44-5778-bf10-7ca3865eaba4","slug":"human-endothelial-oxidant-injury","display_name":"Human endothelial oxidant-associated cell injury","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"8df1dd06-9e0b-510c-8f83-a65757a43068","stable_key":"59b18080-c560-563d-abc5-bac4ee82a27c:ergothioneine-endothelial-entry-loss-event","event_type":"observed_relationship","label":"Protection depended on getting the compound inside.","description":"SLC22A4 siRNA reduced ergothioneine uptake and abolished its cytoprotection in human brain microvascular endothelial cells.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"1509c925-fc5e-5a36-aa59-96bcc489965a","slug":"slc22a4","display_name":"Human ergothioneine transporter OCTN1 / SLC22A4","entity_type_key":"protein"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"bf762512-ad44-5778-bf10-7ca3865eaba4","slug":"human-endothelial-oxidant-injury","display_name":"Human endothelial oxidant-associated cell injury","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"939c92c3-50ea-5a4a-9654-8e3b94448132","slug":"ergothioneine","display_name":"L-Ergothioneine","entity_type_key":"small_molecule"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"38de8704-84db-5770-ac1d-242cd787e798","slug":"sodium-ion","display_name":"Sodium ion","entity_type_key":"ion"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":3,"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":"Cultured human cells challenged with oxidant generators or high glucose.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Transport dependence does not locate ergothioneine inside mitochondria.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Ergothioneine collection; molecular form, preparation, species, exposure and manipulation remain explicit.","comparator":null,"unit":null,"notes":"","entity":{"slug":"ergothioneine","display_name":"L-Ergothioneine","entity_type_key":"small_molecule"}},{"dimension":"plain_language","value_text":"Protection depended on getting the compound inside.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"Uptake and protective effects of ergothioneine in human endothelial cells. · 2014 · https://pubmed.ncbi.nlm.nih.gov/25022513/ · DOI 10.1124/jpet.114.214049","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":"62fed494-aa67-5924-81ce-611c1cbd4141","evidence_kind":"source_excerpt","locator":"Lines 280-286","start_line":280,"end_line":286,"excerpt":"## ergothioneine-endothelial-entry-loss\nProtection depended on getting the compound inside.\nSLC22A4 siRNA reduced ergothioneine uptake and abolished its cytoprotection in human brain microvascular endothelial cells.\nModel: Cultured human cells challenged with oxidant generators or high glucose.\nLimitations: Transport dependence does not locate ergothioneine inside mitochondria.\nEvidence access: Primary abstract\nUptake and protective effects of ergothioneine in human endothelial cells. · 2014 · https://pubmed.ncbi.nlm.nih.gov/25022513/ · DOI 10.1124/jpet.114.214049","model_system":"Cultured human cells challenged with oxidant generators or high glucose.","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":"2f037d98-f3d0-5dbe-80d8-90b738f130d6","stable_key":"import-59b18080-c560-563d-abc5-bac4ee82a27c","title":"Ergothioneine: transport, redox chemistry 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":"b6def8119f03cfabeec2fb55ba924340dc612e1dd42f05404201fa2b7ced5259","revision_id":"f88c38e6-ffb5-5a68-83ca-4610ca2c2df4","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}