{"id":"9dbba5cf-20b3-5cfb-ab95-b08f156e5be7","stable_key":"3279ff78-2460-5064-bfc0-3f2987af85a0:melatonin-retinoid-13cis","predicate":"increases","statement":"The tested retinoic-acid stereoisomer increased HIOMT mRNA and enzyme activity in Y79 cells.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"8c65a79d-228c-5cb2-bece-18e3f0722b9a","mechanism_event_label":"A vitamin-A-derived signaling molecule can regulate this synthetic enzyme in a specific cell model.","subject":{"id":"3d20ca95-a477-578a-b68b-b5c52eaf28be","slug":"13-cis-retinoic-acid","display_name":"13-cis-Retinoic acid / isotretinoin","entity_type_key":"small_molecule"},"object":{"id":"42519c01-e69e-5032-947c-23deb11aba16","slug":"human-asmt-expression","display_name":"Human ASMT mRNA abundance","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"8c65a79d-228c-5cb2-bece-18e3f0722b9a","stable_key":"3279ff78-2460-5064-bfc0-3f2987af85a0:melatonin-retinoid-13cis-event","event_type":"biochemical_relationship","label":"A vitamin-A-derived signaling molecule can regulate this synthetic enzyme in a specific cell model.","description":"The tested retinoic-acid stereoisomer increased HIOMT mRNA and enzyme activity in Y79 cells.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"b903a716-da57-5b63-bb88-7ac032ece84a","slug":"asmt","display_name":"Human acetylserotonin O-methyltransferase / ASMT","entity_type_key":"protein"},"role":"regulated_enzyme","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"3d20ca95-a477-578a-b68b-b5c52eaf28be","slug":"13-cis-retinoic-acid","display_name":"13-cis-Retinoic acid / isotretinoin","entity_type_key":"small_molecule"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"42519c01-e69e-5032-947c-23deb11aba16","slug":"human-asmt-expression","display_name":"Human ASMT mRNA abundance","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""}]},"contexts":[{"dimension":"evidence_span","value_text":"{\"source_cache\": \"artifacts/melatonin-research/8752109.abstract.txt\", \"locator\": \"Primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"d7a80b7b4106efe1c01849e3842ba968626d3a8c5401a5097b617da4d96ce83b\", \"start_char\": 0, \"end_char\": 650, \"text_sha256\": \"d7a80b7b4106efe1c01849e3842ba968626d3a8c5401a5097b617da4d96ce83b\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Retinoid treatment and enzyme/mRNA measurements","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"All-trans, 13-cis and 9-cis retinoic acid exposure","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Tumor-derived cell model. Retinoic acid is not synonymous with dietary vitamin A; no clinical vitamin A repletion or insomnia-treatment inference.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Melatonin research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"melatonin","display_name":"Melatonin","entity_type_key":"small_molecule"}},{"dimension":"organism","value_text":"Human Y79 retinoblastoma-derived cells","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"A vitamin-A-derived signaling molecule can regulate this synthetic enzyme in a specific cell model.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[melatonin-p8752109] Retinoic acid increases hydroxyindole-O-methyltransferase activity and mRNA in human Y-79 retinoblastoma cells. (1996). https://pubmed.ncbi.nlm.nih.gov/8752109/ DOI: 10.1046/j.1471-4159.1996.67031032.x","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"ASMT/HIOMT expression","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"8d5f34cb-adb9-5682-a276-093a50944ae1","evidence_kind":"source_excerpt","locator":"Lines 305-316","start_line":305,"end_line":316,"excerpt":"### melatonin-retinoid-13cis\nThe tested retinoic-acid stereoisomer increased HIOMT mRNA and enzyme activity in Y79 cells.\nCondition category: normal\nnutrient_topic: Melatonin research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: A vitamin-A-derived signaling molecule can regulate this synthetic enzyme in a specific cell model.\norganism: Human Y79 retinoblastoma-derived cells\ntissue_or_cell_type: ASMT/HIOMT expression\nexperimental_model: Retinoid treatment and enzyme/mRNA measurements\nlimitations: Tumor-derived cell model. Retinoic acid is not synonymous with dietary vitamin A; no clinical vitamin A repletion or insomnia-treatment inference.\nexposure: All-trans, 13-cis and 9-cis retinoic acid exposure\nevidence_span: {\"source_cache\": \"artifacts/melatonin-research/8752109.abstract.txt\", \"locator\": \"Primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"d7a80b7b4106efe1c01849e3842ba968626d3a8c5401a5097b617da4d96ce83b\", \"start_char\": 0, \"end_char\": 650, \"text_sha256\": \"d7a80b7b4106efe1c01849e3842ba968626d3a8c5401a5097b617da4d96ce83b\"}\n[melatonin-p8752109] Retinoic acid increases hydroxyindole-O-methyltransferase activity and mRNA in human Y-79 retinoblastoma cells. (1996). https://pubmed.ncbi.nlm.nih.gov/8752109/ DOI: 10.1046/j.1471-4159.1996.67031032.x","model_system":"Retinoid treatment and enzyme/mRNA measurements","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [melatonin-p8752109] Retinoic acid increases hydroxyindole-O-methyltransferase activity and mRNA in human Y-79 retinoblastoma cells. (1996). https://pubmed.ncbi.nlm.nih.gov/8752109/ DOI: 10.1046/j.1471-4159.1996.67031032.x","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"bab588de-d217-5038-9c8b-b41222eba08b","stable_key":"import-3279ff78-2460-5064-bfc0-3f2987af85a0","title":"Melatonin: synthesis, receptors, circadian timing and nutrient interactions (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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