{"id":"00ee1afe-60c0-525c-b5e8-6cfb1f6feb50","stable_key":"35ec55a7-323c-5c28-979e-3bdafe9d5769:nrf2-knockdown-response","predicate":"decreases_in_recorded_experiment","statement":"Nrf2 silencing impaired C3G-associated protection in the palmitate-challenged endothelial model.","claim_class":"observational","status":"source_derived_draft","evidence_grade":"ungraded","direction":"negative","is_public":true,"mechanism_event_id":"10bb0e46-a31e-5256-872c-1877310d4b13","mechanism_event_label":"Nrf2 silencing impaired C3G-associated protection in the palmitate-challenged endothelial model.","subject":{"id":"75149db0-02f7-5d32-8c7a-5c111d90d8ee","slug":"cyanidin-3-glucoside","display_name":"Cyanidin 3-O-beta-D-glucopyranoside","entity_type_key":"small_molecule"},"object":{"id":"b8be0b22-8c9e-5411-8cbe-df365f84cd12","slug":"human-endothelial-insulin-signaling","display_name":"IRS1/PI3K/Akt insulin-signaling readouts in human endothelium","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"10bb0e46-a31e-5256-872c-1877310d4b13","stable_key":"35ec55a7-323c-5c28-979e-3bdafe9d5769:nrf2-knockdown-response-event","event_type":"experimental_observation","label":"Nrf2 silencing impaired C3G-associated protection in the palmitate-challenged endothelial model.","description":"**Nrf2 dependence has been tested, but is context-specific.** C3G pretreatment in palmitate-challenged human endothelial cells improved IRS-1/PI3K/Akt-related insulin signaling and restored eNOS expression and NO release. 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[Fratantonio et al., 2017](https://pubmed.ncbi.nlm.nih.gov/28011403/).","status":"provisional","compartment":null,"participants":[{"entity":{"id":"75149db0-02f7-5d32-8c7a-5c111d90d8ee","slug":"cyanidin-3-glucoside","display_name":"Cyanidin 3-O-beta-D-glucopyranoside","entity_type_key":"small_molecule"},"role":"tested factor","stoichiometry":null,"state_label":"C3G/palmitate experiment with Nrf2 silencing","sequence_order":0,"notes":""},{"entity":{"id":"b8be0b22-8c9e-5411-8cbe-df365f84cd12","slug":"human-endothelial-insulin-signaling","display_name":"IRS1/PI3K/Akt insulin-signaling readouts in human endothelium","entity_type_key":"cellular_process"},"role":"measured outcome","stoichiometry":null,"state_label":"decrease","sequence_order":1,"notes":""},{"entity":{"id":"dc472dd3-d383-567a-ab37-a9ec4e112df4","slug":"nfe2l2","display_name":"Human Nrf2 / NFE2L2","entity_type_key":"protein"},"role":"silenced factor","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"6e161295-1c70-5d1b-8491-9d52c66bea68","slug":"palmitate","display_name":"Palmitate / hexadecanoate","entity_type_key":"small_molecule"},"role":"joint lipid challenge","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""},{"entity":{"id":"d7ab69c0-cd7d-587c-b315-47af56493182","slug":"insulin","display_name":"Insulin","entity_type_key":"protein"},"role":"signaling stimulus","stoichiometry":null,"state_label":"","sequence_order":4,"notes":""}]},"contexts":[{"dimension":"availability_state","value_text":"machinery_impairment","comparator":null,"unit":null,"notes":"Imported condition classification; 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Nrf2 silencing impaired the protective response. This is stronger than merely observing an antioxidant-gene increase, but neither direct KEAP1 binding nor the same action of circulating conjugates follows. The source's exact exposure protocol must accompany any quantitative reuse; only its accessible abstract was extracted here. [Fratantonio et al., 2017](https://pubmed.ncbi.nlm.nih.gov/28011403/).","model_system":"HUVECs with Nrf2 transcript silencing and palmitate challenge.","directness":"reported_statement","verification_status":"source_derived_draft","notes":"Exact excerpt of the retained AI-assisted reviewed reference; primary sources are cited in primary_references and access scope is retained. 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