{"id":"c4139c98-15ad-5671-b110-21da12db0667","stable_key":"6d38d43e-01e4-5641-93be-65654271e242:zinc-trans-zip8-iron-inhibits-zinc","predicate":"inhibits","statement":"A tenfold molar excess of iron inhibited radiolabeled zinc uptake in HEK293T cells expressing rat ZIP8.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"negative","is_public":true,"mechanism_event_id":"cef85554-5483-530a-80f4-7bbad794977f","mechanism_event_label":"Iron reduced zinc entry through this transporter system under the tested culture conditions.","subject":{"id":"59d6d1cd-df32-5b58-b950-3188bc7b95d6","slug":"iron-ii","display_name":"Ferrous iron","entity_type_key":"ion"},"object":{"id":"39158631-eef1-5e08-96a3-385ba1b5acf3","slug":"cellular-zinc-influx","display_name":"Cellular zinc influx","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"cef85554-5483-530a-80f4-7bbad794977f","stable_key":"6d38d43e-01e4-5641-93be-65654271e242:zinc-trans-zip8-iron-inhibits-zinc-event","event_type":"biochemical_relationship","label":"Iron reduced zinc entry through this transporter system under the tested culture conditions.","description":"A tenfold molar excess of iron inhibited radiolabeled zinc uptake in HEK293T cells expressing rat ZIP8.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"ba09e4ed-8b9c-5cd9-bea8-6f8527090978","slug":"rat-slc39a8","display_name":"Rat ZIP8 (Slc39a8)","entity_type_key":"protein"},"role":"transporter","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"49c806c2-7041-5020-8b3b-fa04ffa122ac","slug":"zinc-ion","display_name":"Zinc(II) ion","entity_type_key":"ion"},"role":"inhibited_substrate","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"59d6d1cd-df32-5b58-b950-3188bc7b95d6","slug":"iron-ii","display_name":"Ferrous iron","entity_type_key":"ion"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"39158631-eef1-5e08-96a3-385ba1b5acf3","slug":"cellular-zinc-influx","display_name":"Cellular zinc influx","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""}]},"contexts":[{"dimension":"cross_nutrient","value_text":"true","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Rat ZIP8-expressing HEK293T radiotracer assay","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"2 micromolar labeled zinc and tenfold unlabeled iron excess; uptake medium included ascorbate.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Transport competition in cells is not a universal dietary zinc/iron ratio or a prediction for mixed meals.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Zinc research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"zinc","display_name":"Zinc","entity_type_key":"nutrient_element"}},{"dimension":"organism","value_text":"Rat protein in human cells","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"Iron reduced zinc entry through this transporter system under the tested culture conditions.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[zinc-trans-22898811] ZIP8 is an iron and zinc transporter whose cell-surface expression is up-regulated by cellular iron loading. (2012). https://pubmed.ncbi.nlm.nih.gov/22898811/ DOI: 10.1074/jbc.m112.367284","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"HEK293T cells","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"e1d6b70d-8220-50c4-86ba-918f0dfd0e1c","evidence_kind":"source_excerpt","locator":"Lines 440-451","start_line":440,"end_line":451,"excerpt":"### zinc-trans-zip8-iron-inhibits-zinc\nA tenfold molar excess of iron inhibited radiolabeled zinc uptake in HEK293T cells expressing rat ZIP8.\nCondition category: normal\nnutrient_topic: Zinc research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: Iron reduced zinc entry through this transporter system under the tested culture conditions.\norganism: Rat protein in human cells\ntissue_or_cell_type: HEK293T cells\nexperimental_model: Rat ZIP8-expressing HEK293T radiotracer assay\nlimitations: Transport competition in cells is not a universal dietary zinc/iron ratio or a prediction for mixed meals.\nexposure: 2 micromolar labeled zinc and tenfold unlabeled iron excess; uptake medium included ascorbate.\ncross_nutrient: true\n[zinc-trans-22898811] ZIP8 is an iron and zinc transporter whose cell-surface expression is up-regulated by cellular iron loading. (2012). https://pubmed.ncbi.nlm.nih.gov/22898811/ DOI: 10.1074/jbc.m112.367284","model_system":"Rat ZIP8-expressing HEK293T radiotracer assay","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [zinc-trans-22898811] ZIP8 is an iron and zinc transporter whose cell-surface expression is up-regulated by cellular iron loading. (2012). https://pubmed.ncbi.nlm.nih.gov/22898811/ DOI: 10.1074/jbc.m112.367284","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"c5ee0fee-ce5c-58de-905a-10fb0ea0723c","stable_key":"import-6d38d43e-01e4-5641-93be-65654271e242","title":"Zinc: transport, enzyme loading, deficiency 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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