{"id":"83cc4666-734e-5dc7-8c60-0028d46fae79","stable_key":"d8050016-13c9-5391-9d61-63de73590053:zeaxanthin-gclm-expression","predicate":"increases_transcript_of","statement":"Zeaxanthin increased GCLM mRNA in ARPE-19 cells.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"2e1ad0b0-06cb-5ea9-b912-f6feaaf7fab0","mechanism_event_label":"The regulatory subunit also responded.","subject":{"id":"0a60c685-7502-5ece-9da2-2c1a2e3bcdf1","slug":"zeaxanthin","display_name":"Dietary (3R,3-prime-R)-zeaxanthin","entity_type_key":"small_molecule"},"object":{"id":"2be894ac-8d47-565b-94f3-f12fdc993c3f","slug":"gclm","display_name":"Human glutamate-cysteine ligase modifier subunit / GCLM","entity_type_key":"protein"},"evidence_count":1,"mechanism_event":{"id":"2e1ad0b0-06cb-5ea9-b912-f6feaaf7fab0","stable_key":"d8050016-13c9-5391-9d61-63de73590053:zeaxanthin-gclm-expression-event","event_type":"biochemical_relationship","label":"The regulatory subunit also responded.","description":"Zeaxanthin increased GCLM mRNA in ARPE-19 cells.","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":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"2be894ac-8d47-565b-94f3-f12fdc993c3f","slug":"gclm","display_name":"Human glutamate-cysteine ligase modifier subunit / GCLM","entity_type_key":"protein"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"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":"The regulatory subunit also responded.","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. (2014). https://pubmed.ncbi.nlm.nih.gov/24810054/ DOI: 10.1038/cddis.2014.190","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Retinal pigment epithelial model","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"266790af-94e0-5679-b524-368a1136e326","evidence_kind":"source_excerpt","locator":"Lines 392-403","start_line":392,"end_line":403,"excerpt":"### zeaxanthin-gclm-expression\nZeaxanthin increased GCLM mRNA in ARPE-19 cells.\nCondition category: normal\nnutrient_topic: Zeaxanthin research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: The regulatory subunit also responded.\norganism: Human ARPE-19 cell line\ntissue_or_cell_type: Retinal pigment epithelial model\nexperimental_model: Cell challenge with siRNA and pathway inhibitors\nlimitations: 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.\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. (2014). https://pubmed.ncbi.nlm.nih.gov/24810054/ DOI: 10.1038/cddis.2014.190","model_system":"Cell challenge with siRNA and pathway inhibitors","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [zeaxanthin-p24810054] Zeaxanthin induces Nrf2-mediated phase II enzymes in protection of cell death. (2014). https://pubmed.ncbi.nlm.nih.gov/24810054/ DOI: 10.1038/cddis.2014.190","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"df7effe5-d60c-525e-bd48-1518e1a03c51","stable_key":"import-d8050016-13c9-5391-9d61-63de73590053","title":"Zeaxanthin: metabolism, signaling and nutrient connections (2026-09-17)","document_type":"imported_text","citation_label":"AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. 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