{"id":"eaf3d7af-e0f1-511d-beb2-1beca9e53955","stable_key":"d8050016-13c9-5391-9d61-63de73590053:zeaxanthin-nrf2-failure","predicate":"reduces","statement":"Nrf2 knockdown suppressed zeaxanthin-induced glutathione accumulation.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"2db8e40a-b486-5bb7-9e2b-aaccf45df2a0","mechanism_event_label":"Adding pigment could not fully replace the missing regulatory machinery.","subject":{"id":"bc697dff-6755-5447-9db1-e714fef23a7b","slug":"nfe2l2-knockdown","display_name":"Experimental human NFE2L2 knockdown","entity_type_key":"protein_state"},"object":{"id":"374b1b09-8e8f-5379-8168-239b3898a4c9","slug":"human-rpe-glutathione-pool","display_name":"Glutathione pool in human ARPE-19 cells","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"2db8e40a-b486-5bb7-9e2b-aaccf45df2a0","stable_key":"d8050016-13c9-5391-9d61-63de73590053:zeaxanthin-nrf2-failure-event","event_type":"biochemical_relationship","label":"Adding pigment could not fully replace the missing regulatory machinery.","description":"Nrf2 knockdown suppressed zeaxanthin-induced glutathione accumulation.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"0a60c685-7502-5ece-9da2-2c1a2e3bcdf1","slug":"zeaxanthin","display_name":"Dietary (3R,3-prime-R)-zeaxanthin","entity_type_key":"small_molecule"},"role":"tested_intervention","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"dc472dd3-d383-567a-ab37-a9ec4e112df4","slug":"nfe2l2","display_name":"Human Nrf2 / NFE2L2","entity_type_key":"protein"},"role":"affected_protein","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"bc697dff-6755-5447-9db1-e714fef23a7b","slug":"nfe2l2-knockdown","display_name":"Experimental human NFE2L2 knockdown","entity_type_key":"protein_state"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"374b1b09-8e8f-5379-8168-239b3898a4c9","slug":"human-rpe-glutathione-pool","display_name":"Glutathione pool in human ARPE-19 cells","entity_type_key":"cellular_process"},"role":"target","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_span","value_text":"{\"source_cache\": \"artifacts/zeaxanthin-research/24810054.fulltext.txt\", \"locator\": \"Primary full-text span; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"0f185c805dd5d825445cb40e547b794fbc595388aff6e2d29ac81c2eab8b8348\", \"start_char\": 5813, \"end_char\": 15716, \"text_sha256\": \"89e6abf1967c10b359cb62d935d5b839cf53acf42576d9db3d463bff9f474e38\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Cell challenge with siRNA and pathway inhibitors","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Zeaxanthin commonly 10 micromolar for 24 h; 300 micromolar t-BHP challenge for 6 h; study-specific inhibitors","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Pharmacological cell exposures are not dietary concentrations. PI3K/Akt inhibitor evidence is not direct zeaxanthin binding to a kinase. Liposome GSTP1 protection and this cellular GSH-dependent response are different mechanisms.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Zeaxanthin research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"zeaxanthin","display_name":"Dietary (3R,3-prime-R)-zeaxanthin","entity_type_key":"small_molecule"}},{"dimension":"organism","value_text":"Human ARPE-19 cell line","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"Adding pigment could not fully replace the missing regulatory machinery.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[zeaxanthin-p24810054] Zeaxanthin induces Nrf2-mediated phase II enzymes in protection of cell death. 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PI3K/Akt inhibitor evidence is not direct zeaxanthin binding to a kinase. Liposome GSTP1 protection and this cellular GSH-dependent response are different mechanisms.\nexposure: Zeaxanthin commonly 10 micromolar for 24 h; 300 micromolar t-BHP challenge for 6 h; study-specific inhibitors\nevidence_span: {\"source_cache\": \"artifacts/zeaxanthin-research/24810054.fulltext.txt\", \"locator\": \"Primary full-text span; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"0f185c805dd5d825445cb40e547b794fbc595388aff6e2d29ac81c2eab8b8348\", \"start_char\": 5813, \"end_char\": 15716, \"text_sha256\": \"89e6abf1967c10b359cb62d935d5b839cf53acf42576d9db3d463bff9f474e38\"}\n[zeaxanthin-p24810054] Zeaxanthin induces Nrf2-mediated phase II enzymes in protection of cell death. 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