{"id":"c13aa239-ff88-5b91-9736-e937b55d9117","stable_key":"cb568d28-484a-5c2e-9fcc-2d780358e514:vc-enzyme-neuronal-th-protein","predicate":"increases-protein-abundance","statement":"In pooled SH-SY5Y immunoblots after 24 hours, TH protein rose to a maximum around 170% of control; statistical significance in Results/Fig.4 was reached at 1000 micromolar loading ascorbate (approximately 1.6–2.5 mM intracellular).","claim_class":"observational","status":"source_derived_draft","evidence_grade":"ungraded","direction":"positive","is_public":true,"mechanism_event_id":"730f34c4-dc68-5613-83a6-003b9b79cd83","mechanism_event_label":"At the tested higher exposure, vitamin C increased the amount of an enzyme upstream of dopamine synthesis.","subject":{"id":"38d0c4d9-53d1-5239-bfe3-c1b5e9b79085","slug":"ascorbate","display_name":"L-Ascorbate","entity_type_key":"small_molecule"},"object":{"id":"e4e0f24b-1e70-573d-b719-039a90191b90","slug":"human-tyrosine-hydroxylase","display_name":"Human tyrosine hydroxylase","entity_type_key":"protein"},"evidence_count":1,"mechanism_event":{"id":"730f34c4-dc68-5613-83a6-003b9b79cd83","stable_key":"cb568d28-484a-5c2e-9fcc-2d780358e514:vc-enzyme-neuronal-th-protein-event","event_type":"observed_intervention","label":"At the tested higher exposure, vitamin C increased the amount of an enzyme upstream of dopamine synthesis.","description":"In pooled SH-SY5Y immunoblots after 24 hours, TH protein rose to a maximum around 170% of control; statistical significance in Results/Fig.4 was reached at 1000 micromolar loading ascorbate (approximately 1.6–2.5 mM intracellular).","status":"provisional","compartment":null,"participants":[{"entity":{"id":"38d0c4d9-53d1-5239-bfe3-c1b5e9b79085","slug":"ascorbate","display_name":"L-Ascorbate","entity_type_key":"small_molecule"},"role":"supporting-reductant","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"e4e0f24b-1e70-573d-b719-039a90191b90","slug":"human-tyrosine-hydroxylase","display_name":"Human tyrosine hydroxylase","entity_type_key":"protein"},"role":"measured-protein","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""}]},"contexts":[{"dimension":"cross_nutrient","value_text":"Vitamin C chemistry in collagen, modified-lysine/carnitine metabolism or copper-dependent peptide/catecholamine processing.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Human SH-SY5Y neuroblastoma cultures","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"24-hour cell culture; 1000 micromolar medium loading reaches significance in pooled Fig.4B; intracellular approximately 1.6–2.5 mM.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Results/Fig.4 exposure is retained because Discussion describes significant effects at lower loading concentrations. No universal neuronal vitamin C threshold established.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Vitamin C research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"vitamin-c","display_name":"Vitamin C","entity_type_key":"chemical_species"}},{"dimension":"organism","value_text":"Homo sapiens","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"At the tested higher exposure, vitamin C increased the amount of an enzyme upstream of dopamine synthesis.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[may2012] Mechanisms of ascorbic acid stimulation of norepinephrine synthesis in neuronal cells. (2012). https://pubmed.ncbi.nlm.nih.gov/22925890/ DOI: 10.1016/j.bbrc.2012.08.054","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Neuronal tumor cell line","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"10376916-531e-5d6b-adbd-72ec302f33c3","evidence_kind":"source_excerpt","locator":"Lines 833-844","start_line":833,"end_line":844,"excerpt":"### vc-enzyme-neuronal-th-protein\nIn pooled SH-SY5Y immunoblots after 24 hours, TH protein rose to a maximum around 170% of control; statistical significance in Results/Fig.4 was reached at 1000 micromolar loading ascorbate (approximately 1.6–2.5 mM intracellular).\nCondition category: normal\nnutrient_topic: Vitamin C research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: At the tested higher exposure, vitamin C increased the amount of an enzyme upstream of dopamine synthesis.\norganism: Homo sapiens\ntissue_or_cell_type: Neuronal tumor cell line\nexperimental_model: Human SH-SY5Y neuroblastoma cultures\nlimitations: Results/Fig.4 exposure is retained because Discussion describes significant effects at lower loading concentrations. No universal neuronal vitamin C threshold established.\ncross_nutrient: Vitamin C chemistry in collagen, modified-lysine/carnitine metabolism or copper-dependent peptide/catecholamine processing.\nexposure: 24-hour cell culture; 1000 micromolar medium loading reaches significance in pooled Fig.4B; intracellular approximately 1.6–2.5 mM.\n[may2012] Mechanisms of ascorbic acid stimulation of norepinephrine synthesis in neuronal cells. (2012). https://pubmed.ncbi.nlm.nih.gov/22925890/ DOI: 10.1016/j.bbrc.2012.08.054","model_system":"Human SH-SY5Y neuroblastoma cultures","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [may2012] Mechanisms of ascorbic acid stimulation of norepinephrine synthesis in neuronal cells. 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