{"id":"ec0ee083-7f23-5479-84d4-c5612d51f2c7","stable_key":"488ea171-36b8-5ef6-b5d3-98563980fdbf:hbot-ascorbate-suppresses-hif","predicate":"reduces","statement":"Ascorbate inhibited HIF-1 activity most dramatically under all mechanisms of iron competition, and HIF-1-dependent gene expression was prevented even under conditions that allowed HIF-1alpha protein stabilisation.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"negative","is_public":true,"mechanism_event_id":"67b6edcc-c755-53de-99ac-5f4fbc4cf05b","mechanism_event_label":"Vitamin C shuts down the low-oxygen gene programme even when the protein itself survives.","subject":{"id":"38d0c4d9-53d1-5239-bfe3-c1b5e9b79085","slug":"ascorbate","display_name":"L-Ascorbate","entity_type_key":"small_molecule"},"object":{"id":"b1207f94-96eb-5134-8055-cfd9881c106e","slug":"hif1-transcriptional-activity","display_name":"HIF-1 transcriptional activity","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"67b6edcc-c755-53de-99ac-5f4fbc4cf05b","stable_key":"488ea171-36b8-5ef6-b5d3-98563980fdbf:hbot-ascorbate-suppresses-hif-event","event_type":"biochemical_relationship","label":"Vitamin C shuts down the low-oxygen gene programme even when the protein itself survives.","description":"Ascorbate inhibited HIF-1 activity most dramatically under all mechanisms of iron competition, and HIF-1-dependent gene expression was prevented even under conditions that allowed HIF-1alpha protein stabilisation.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"c0b7fa17-9b1d-5828-b394-a7fc08a797f3","slug":"ferrous-iron","display_name":"Ferrous iron / Fe(II)","entity_type_key":"ion"},"role":"competed_metal","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"89bcaf42-b4ab-5760-8c2e-44eace10cee0","slug":"iron","display_name":"Iron","entity_type_key":"nutrient_element"},"role":"nutrient_source","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"38ab3e53-0fab-5e1c-99e9-13f579be2d92","slug":"fih","display_name":"Factor inhibiting HIF / FIH asparaginyl hydroxylase","entity_type_key":"protein"},"role":"susceptible_enzyme","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"38d0c4d9-53d1-5239-bfe3-c1b5e9b79085","slug":"ascorbate","display_name":"L-Ascorbate","entity_type_key":"small_molecule"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""},{"entity":{"id":"b1207f94-96eb-5134-8055-cfd9881c106e","slug":"hif1-transcriptional-activity","display_name":"HIF-1 transcriptional activity","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":4,"notes":""}]},"contexts":[{"dimension":"evidence_span","value_text":"{\"source_cache\": \"artifacts/hbot-research/24495550.abstract.txt\", \"locator\": \"Indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"444b204ff84635f64eebf59c2db6afa112641b24f7b309fb2bcd6da04d4d0d0a\", \"start_char\": 0, \"end_char\": 1497, \"text_sha256\": \"444b204ff84635f64eebf59c2db6afa112641b24f7b309fb2bcd6da04d4d0d0a\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Cells with defined intracellular ascorbate concentrations against several hydroxylase inhibitors","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Intracellular ascorbate loading with CoCl2, NiCl2, desferrioxamine, dimethyloxalylglycine or hypoxia","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Establishes an effect of intracellular ascorbate on the HIF response. The iron-competing inhibitors are the conditions where ascorbate mattered most.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake.","comparator":null,"unit":null,"notes":"","entity":{"slug":"hyperbaric-oxygen","display_name":"Hyperbaric oxygen therapy","entity_type_key":"drug"}},{"dimension":"organism","value_text":"Human cells","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"Vitamin C shuts down the low-oxygen gene programme even when the protein itself survives.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[hbot-p24495550] Intracellular ascorbate enhances hypoxia-inducible factor (HIF)-hydroxylase activity and preferentially suppresses the HIF-1 transcriptional response. (2014). https://pubmed.ncbi.nlm.nih.gov/24495550/ DOI: 10.1016/j.freeradbiomed.2014.01.033","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Cytosol and nucleus","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"a8472f2d-5324-5773-adc1-65fbf7b667d9","evidence_kind":"source_excerpt","locator":"Lines 985-996","start_line":985,"end_line":996,"excerpt":"### hbot-ascorbate-suppresses-hif\nAscorbate inhibited HIF-1 activity most dramatically under all mechanisms of iron competition, and HIF-1-dependent gene expression was prevented even under conditions that allowed HIF-1alpha protein stabilisation.\nCondition category: normal\nnutrient_topic: Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake.\nplain_language: Vitamin C shuts down the low-oxygen gene programme even when the protein itself survives.\norganism: Human cells\ntissue_or_cell_type: Cytosol and nucleus\nexperimental_model: Cells with defined intracellular ascorbate concentrations against several hydroxylase inhibitors\nlimitations: Establishes an effect of intracellular ascorbate on the HIF response. The iron-competing inhibitors are the conditions where ascorbate mattered most.\nexposure: Intracellular ascorbate loading with CoCl2, NiCl2, desferrioxamine, dimethyloxalylglycine or hypoxia\nevidence_span: {\"source_cache\": \"artifacts/hbot-research/24495550.abstract.txt\", \"locator\": \"Indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"444b204ff84635f64eebf59c2db6afa112641b24f7b309fb2bcd6da04d4d0d0a\", \"start_char\": 0, \"end_char\": 1497, \"text_sha256\": \"444b204ff84635f64eebf59c2db6afa112641b24f7b309fb2bcd6da04d4d0d0a\"}\n[hbot-p24495550] Intracellular ascorbate enhances hypoxia-inducible factor (HIF)-hydroxylase activity and preferentially suppresses the HIF-1 transcriptional response. (2014). https://pubmed.ncbi.nlm.nih.gov/24495550/ DOI: 10.1016/j.freeradbiomed.2014.01.033","model_system":"Cells with defined intracellular ascorbate concentrations against several hydroxylase inhibitors","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [hbot-p24495550] Intracellular ascorbate enhances hypoxia-inducible factor (HIF)-hydroxylase activity and preferentially suppresses the HIF-1 transcriptional response. (2014). https://pubmed.ncbi.nlm.nih.gov/24495550/ DOI: 10.1016/j.freeradbiomed.2014.01.033","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"dbf39b48-c95e-5291-b404-349ffbc4488f","stable_key":"import-488ea171-36b8-5ef6-b5d3-98563980fdbf","title":"Hyperbaric oxygen: the exposure, its reactive species, the signals they carry, and the nutrient-dependent enzymes that handle them (2026-09-19)","document_type":"imported_text","citation_label":"AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text.","file_path":"","sha256":"fb2443321804010d82c6b96ab61cc51b4b6628ddbb15751cb0e90b491606e79c","revision_id":"bb699ea5-b492-5728-b22c-48f0842a8ac9","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}