{"id":"89761135-edf7-517c-b2d8-a55ab5a2830a","stable_key":"74ef5bba-ee14-531c-b1bf-d1f297c56bb6:fisetin-cardiac-sirt1-block","predicate":"inhibition_reduces","statement":"SIRT1 inhibition attenuated fisetin protection in doxorubicin-exposed H9c2 cells and reduced the associated GSH/GPX4 response.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"1410f776-0d1a-57ba-8ddd-9f9e321faa48","mechanism_event_label":"An intact regulatory pathway was required for the full response.","subject":{"id":"46cd9ecc-a60b-592a-a095-9645baeb18a6","slug":"rat-sirt1","display_name":"Rat sirtuin 1 / Sirt1","entity_type_key":"protein"},"object":{"id":"e1691542-05e3-5187-ba2e-06a0ff68e100","slug":"rat-h9c2-fisetin-cardioprotection","display_name":"Fisetin-associated protection in rat H9c2 cells","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"1410f776-0d1a-57ba-8ddd-9f9e321faa48","stable_key":"74ef5bba-ee14-531c-b1bf-d1f297c56bb6:fisetin-cardiac-sirt1-block-event","event_type":"observed_relationship","label":"An intact regulatory pathway was required for the full response.","description":"SIRT1 inhibition attenuated fisetin protection in doxorubicin-exposed H9c2 cells and reduced the associated GSH/GPX4 response.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"46cd9ecc-a60b-592a-a095-9645baeb18a6","slug":"rat-sirt1","display_name":"Rat sirtuin 1 / Sirt1","entity_type_key":"protein"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"e1691542-05e3-5187-ba2e-06a0ff68e100","slug":"rat-h9c2-fisetin-cardioprotection","display_name":"Fisetin-associated protection in rat H9c2 cells","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"dee05061-c3f3-5226-8054-dd58b76a585d","slug":"fisetin","display_name":"Fisetin","entity_type_key":"small_molecule"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"cc0ebb24-b978-598b-a9aa-8c5b99eab542","slug":"rat-gpx4","display_name":"Rat glutathione peroxidase 4 / Gpx4","entity_type_key":"protein"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""},{"entity":{"id":"b44c9e27-4bbb-52d3-a022-14cddded5073","slug":"glutathione","display_name":"GSH","entity_type_key":"small_molecule"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":4,"notes":""},{"entity":{"id":"27636f1d-fd51-5697-a8bb-6c827f4f8b40","slug":"rat-nfe2l2","display_name":"Rat Nrf2 / Nfe2l2","entity_type_key":"protein"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":5,"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":"Rat cardiac-cell pharmacological inhibition.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Not proof that niacin or NAD supplements enhance fisetin.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Fisetin collection; molecular form, preparation, species, exposure and manipulation remain explicit.","comparator":null,"unit":null,"notes":"","entity":{"slug":"fisetin","display_name":"Fisetin","entity_type_key":"small_molecule"}},{"dimension":"plain_language","value_text":"An intact regulatory pathway was required for the full response.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"Fisetin Attenuates Doxorubicin-Induced Cardiomyopathy In Vivo and In Vitro by Inhibiting Ferroptosis Through SIRT1/Nrf2 Signaling Pathway Activation. · 2021 · https://pubmed.ncbi.nlm.nih.gov/35273493/ · DOI 10.3389/fphar.2021.808480","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"trigger_kind","value_text":"machinery_impairment","comparator":null,"unit":null,"notes":"Imported condition classification; 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