{"id":"202b49b5-df13-522d-805b-ecbce24f0bbf","stable_key":"59b18080-c560-563d-abc5-bac4ee82a27c:ergothioneine-sirtuin-dependence","predicate":"abolishes_protection_against","statement":"SIRT1 activity inhibition or SIRT6 siRNA abolished ergothioneine protection against high-glucose-induced endothelial senescence.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"dc5e4892-7272-55b3-9642-8229dedfe268","mechanism_event_label":"Blocking the regulatory machinery removed protection.","subject":{"id":"54183d3d-058e-5f78-bedc-923fdad2c823","slug":"endothelial-sirtuin-perturbation","display_name":"SIRT1 inhibition or SIRT6 silencing in endothelial assay","entity_type_key":"cellular_process"},"object":{"id":"ea7b8a7f-a947-5e11-a37b-e89d9e78c5c5","slug":"endothelial-high-glucose-senescence","display_name":"Endothelial-cell high-glucose-induced senescence, preparation specified","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"dc5e4892-7272-55b3-9642-8229dedfe268","stable_key":"59b18080-c560-563d-abc5-bac4ee82a27c:ergothioneine-sirtuin-dependence-event","event_type":"observed_relationship","label":"Blocking the regulatory machinery removed protection.","description":"SIRT1 activity inhibition or SIRT6 siRNA abolished ergothioneine protection against high-glucose-induced endothelial senescence.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"54183d3d-058e-5f78-bedc-923fdad2c823","slug":"endothelial-sirtuin-perturbation","display_name":"SIRT1 inhibition or SIRT6 silencing in endothelial assay","entity_type_key":"cellular_process"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"ea7b8a7f-a947-5e11-a37b-e89d9e78c5c5","slug":"endothelial-high-glucose-senescence","display_name":"Endothelial-cell high-glucose-induced senescence, preparation specified","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":"7dc0b10c-0146-532c-bc56-b693f38a4013","slug":"endothelial-assay-sirt1","display_name":"SIRT1 in endothelial high-glucose study, species unresolved","entity_type_key":"protein"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""},{"entity":{"id":"263ba437-95b0-5dd3-bf21-00b6c53c33b1","slug":"endothelial-assay-sirt6","display_name":"SIRT6 in endothelial high-glucose study, species unresolved","entity_type_key":"protein"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":4,"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":"Endothelial-cell pharmacological and genetic perturbation.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Dependence is stronger than expression association, but does not show direct binding or supply of NAD.","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":"Blocking the regulatory machinery removed protection.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"Ergothioneine oxidation in the protection against high-glucose induced endothelial senescence: Involvement of SIRT1 and SIRT6. · 2016 · https://pubmed.ncbi.nlm.nih.gov/27101740/ · DOI 10.1016/j.freeradbiomed.2016.04.013","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":"85a0ab68-3002-5135-9729-eef50fbde072","evidence_kind":"source_excerpt","locator":"Lines 360-366","start_line":360,"end_line":366,"excerpt":"## ergothioneine-sirtuin-dependence\nBlocking the regulatory machinery removed protection.\nSIRT1 activity inhibition or SIRT6 siRNA abolished ergothioneine protection against high-glucose-induced endothelial senescence.\nModel: Endothelial-cell pharmacological and genetic perturbation.\nLimitations: Dependence is stronger than expression association, but does not show direct binding or supply of NAD.\nEvidence access: Primary abstract\nErgothioneine oxidation in the protection against high-glucose induced endothelial senescence: Involvement of SIRT1 and SIRT6. · 2016 · https://pubmed.ncbi.nlm.nih.gov/27101740/ · DOI 10.1016/j.freeradbiomed.2016.04.013","model_system":"Endothelial-cell pharmacological and genetic perturbation.","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. 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