{"id":"f85f91a0-8659-5be9-9920-9e72aa87eb2c","stable_key":"a9dd23c6-978a-5755-8bd8-f29bd1fe0cda:nia-clin-arrb1-pla2","predicate":"supports_nicotinic_acid_activation_of","statement":"Nicotinic acid promoted beta-arrestin1 association with activated cytosolic phospholipase A2 and beta-arrestin1-dependent phospholipase activation with arachidonate release in the cell assay.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"positive","is_public":true,"mechanism_event_id":"6431675f-5606-5b08-a7d8-5b20bd0f41d0","mechanism_event_label":"A separate receptor branch recruits beta-arrestin and releases the fatty-acid material used to make flushing signals.","subject":{"id":"ca41fb71-afc3-55ee-a74b-0b6da9f6b08f","slug":"arrb1","display_name":"Human beta-arrestin 1 / ARRB1","entity_type_key":"protein"},"object":{"id":"2f23ad73-9b91-52de-99e9-40d6ca906792","slug":"pla2g4a","display_name":"Human cytosolic phospholipase A2 alpha / PLA2G4A","entity_type_key":"protein"},"evidence_count":1,"mechanism_event":{"id":"6431675f-5606-5b08-a7d8-5b20bd0f41d0","stable_key":"a9dd23c6-978a-5755-8bd8-f29bd1fe0cda:nia-clin-arrb1-pla2-event","event_type":"biochemical_relationship","label":"A separate receptor branch recruits beta-arrestin and releases the fatty-acid material used to make flushing signals.","description":"Nicotinic acid promoted beta-arrestin1 association with activated cytosolic phospholipase A2 and beta-arrestin1-dependent phospholipase activation with arachidonate release in the cell assay.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"c31b5501-5abf-57bb-8324-15923ed678cf","slug":"hcar2","display_name":"Human hydroxycarboxylic acid receptor 2 / HCAR2","entity_type_key":"protein"},"role":"upstream_receptor","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"9751fdb6-9b30-586f-b07a-79b8e2cd62dd","slug":"nicotinic-acid","display_name":"Nicotinic acid","entity_type_key":"small_molecule"},"role":"agonist","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"39f9446f-52a6-502d-b507-91137726f82c","slug":"arachidonic-acid","display_name":"AA","entity_type_key":"small_molecule"},"role":"released_substrate","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"ca41fb71-afc3-55ee-a74b-0b6da9f6b08f","slug":"arrb1","display_name":"Human beta-arrestin 1 / ARRB1","entity_type_key":"protein"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""},{"entity":{"id":"2f23ad73-9b91-52de-99e9-40d6ca906792","slug":"pla2g4a","display_name":"Human cytosolic phospholipase A2 alpha / PLA2G4A","entity_type_key":"protein"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":4,"notes":""}]},"contexts":[{"dimension":"cross_nutrient","value_text":"Human hydroxycarboxylic acid receptor 2 / HCAR2 (upstream_receptor); Nicotinic acid (agonist); arachidonic acid (released_substrate)","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"evidence_span","value_text":"{\"source_cache\": \"artifacts/niacin-clinical-sources/walters2009.abstract.txt\", \"locator\": \"Indexed primary abstract\", \"file_sha256\": \"2eb822534ed0c8ea9f71ec67288c302e4e375ed9e86cfe70b28f21ae65ffbd4b\", \"start_char\": 0, \"end_char\": 1537, \"text_sha256\": \"2eb822534ed0c8ea9f71ec67288c302e4e375ed9e86cfe70b28f21ae65ffbd4b\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Human cell-line nicotinic-acid receptor signaling assay","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Nicotinic-acid stimulation and beta-arrestin perturbation","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Pharmacological receptor signaling, not an essential effect of every B3 precursor. Cell signaling and mouse physiology are distinct arms. Reduced fatty acids or flushing does not establish cardiovascular benefit.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Niacin research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"niacin","display_name":"Niacin (vitamin B3)","entity_type_key":"nutrient_element"}},{"dimension":"organism","value_text":"Homo sapiens","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"A separate receptor branch recruits beta-arrestin and releases the fatty-acid material used to make flushing signals.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[nia-clin-walters2009] beta-Arrestin1 mediates nicotinic acid-induced flushing, but not its antilipolytic effect, in mice. (2009). https://pubmed.ncbi.nlm.nih.gov/19349687/ DOI: 10.1172/jci36806","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Cultured human cells","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"ac2a5f53-8e13-53c8-8938-a639c6355d8d","evidence_kind":"source_excerpt","locator":"Lines 1305-1317","start_line":1305,"end_line":1317,"excerpt":"### nia-clin-arrb1-pla2\nNicotinic acid promoted beta-arrestin1 association with activated cytosolic phospholipase A2 and beta-arrestin1-dependent phospholipase activation with arachidonate release in the cell assay.\nCondition category: normal\nnutrient_topic: Niacin research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: A separate receptor branch recruits beta-arrestin and releases the fatty-acid material used to make flushing signals.\norganism: Homo sapiens\ntissue_or_cell_type: Cultured human cells\nexperimental_model: Human cell-line nicotinic-acid receptor signaling assay\nlimitations: Pharmacological receptor signaling, not an essential effect of every B3 precursor. Cell signaling and mouse physiology are distinct arms. Reduced fatty acids or flushing does not establish cardiovascular benefit.\nexposure: Nicotinic-acid stimulation and beta-arrestin perturbation\ncross_nutrient: Human hydroxycarboxylic acid receptor 2 / HCAR2 (upstream_receptor); Nicotinic acid (agonist); arachidonic acid (released_substrate)\nevidence_span: {\"source_cache\": \"artifacts/niacin-clinical-sources/walters2009.abstract.txt\", \"locator\": \"Indexed primary abstract\", \"file_sha256\": \"2eb822534ed0c8ea9f71ec67288c302e4e375ed9e86cfe70b28f21ae65ffbd4b\", \"start_char\": 0, \"end_char\": 1537, \"text_sha256\": \"2eb822534ed0c8ea9f71ec67288c302e4e375ed9e86cfe70b28f21ae65ffbd4b\"}\n[nia-clin-walters2009] beta-Arrestin1 mediates nicotinic acid-induced flushing, but not its antilipolytic effect, in mice. 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