{"id":"5df76b82-b4e1-5df3-bd9d-8420c5cdf948","stable_key":"d8050016-13c9-5391-9d61-63de73590053:zeaxanthin-pi3k-block","predicate":"abolishes_protection_of","statement":"LY294002 blocked zeaxanthin-associated survival protection; U0126 did not show the same effect.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"bb50c8d1-04fe-5c4d-9645-b14b0c449282","mechanism_event_label":"Activating a pathway and needing it for protection are different tests.","subject":{"id":"2e2e42db-847b-5248-b05a-ac5afed107b1","slug":"ly294002","display_name":"LY294002","entity_type_key":"small_molecule"},"object":{"id":"31a83bcc-0ab9-5073-9d6a-f570dfb6ab68","slug":"arpe19-tbhp-survival","display_name":"ARPE-19 survival after tert-butyl hydroperoxide challenge","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"bb50c8d1-04fe-5c4d-9645-b14b0c449282","stable_key":"d8050016-13c9-5391-9d61-63de73590053:zeaxanthin-pi3k-block-event","event_type":"biochemical_relationship","label":"Activating a pathway and needing it for protection are different tests.","description":"LY294002 blocked zeaxanthin-associated survival protection; U0126 did not show the same effect.","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":"359979da-c958-50bf-b2f7-9f15e177fa5d","slug":"pi3k-family","display_name":"Phosphoinositide 3-kinase family","entity_type_key":"protein_family"},"role":"inhibitor_target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"a13cb592-c939-5f92-9206-d774248802fc","slug":"akt-proteins","display_name":"AKT serine/threonine kinase family","entity_type_key":"protein_family"},"role":"pathway_component","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"2944ff54-7d74-5b34-bc0c-c77ac1444717","slug":"erk1-2","display_name":"ERK1/2 proteins, isoform not resolved","entity_type_key":"protein_family"},"role":"comparison_pathway","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""},{"entity":{"id":"9827a659-c7a9-5709-b251-e8c6082bd8f6","slug":"u0126","display_name":"U0126 MEK-pathway inhibitor","entity_type_key":"small_molecule"},"role":"comparison_inhibitor","stoichiometry":null,"state_label":"","sequence_order":4,"notes":""},{"entity":{"id":"2e2e42db-847b-5248-b05a-ac5afed107b1","slug":"ly294002","display_name":"LY294002","entity_type_key":"small_molecule"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":5,"notes":""},{"entity":{"id":"31a83bcc-0ab9-5073-9d6a-f570dfb6ab68","slug":"arpe19-tbhp-survival","display_name":"ARPE-19 survival after tert-butyl hydroperoxide challenge","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":6,"notes":""}]},"contexts":[{"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":"Activating a pathway and needing it for protection are different tests.","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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