{"id":"d094d794-96bd-5fca-8f3a-241832c41dd2","stable_key":"6d38d43e-01e4-5641-93be-65654271e242:zinc-trans-zip8-placental-iron","predicate":"supports","statement":"Suppressing endogenous human ZIP8 in BeWo placental cells reduced iron uptake by approximately 40%.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"positive","is_public":true,"mechanism_event_id":"02bc06de-a8e1-5473-8300-2957608af3a9","mechanism_event_label":"ZIP8 contributed to iron entry in a human placental cell model.","subject":{"id":"059eea33-6e24-58ca-970f-014e2e65df77","slug":"slc39a8","display_name":"Human ZIP8 (SLC39A8)","entity_type_key":"protein"},"object":{"id":"a8f23a2f-dee3-537a-b86d-620681c5d6ca","slug":"placental-cell-iron-uptake","display_name":"Placental-cell iron uptake","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"02bc06de-a8e1-5473-8300-2957608af3a9","stable_key":"6d38d43e-01e4-5641-93be-65654271e242:zinc-trans-zip8-placental-iron-event","event_type":"biochemical_relationship","label":"ZIP8 contributed to iron entry in a human placental cell model.","description":"Suppressing endogenous human ZIP8 in BeWo placental cells reduced iron uptake by approximately 40%.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"59d6d1cd-df32-5b58-b950-3188bc7b95d6","slug":"iron-ii","display_name":"Ferrous iron","entity_type_key":"ion"},"role":"transported_substrate","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":"shared_transporter_cargo_context","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"059eea33-6e24-58ca-970f-014e2e65df77","slug":"slc39a8","display_name":"Human ZIP8 (SLC39A8)","entity_type_key":"protein"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"a8f23a2f-dee3-537a-b86d-620681c5d6ca","slug":"placental-cell-iron-uptake","display_name":"Placental-cell iron uptake","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""}]},"contexts":[{"dimension":"availability_state","value_text":"machinery_impairment","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null},{"dimension":"cross_nutrient","value_text":"true","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"ZIP8 suppression in BeWo trophoblast-derived cells","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Endogenous ZIP8 knockdown compared with controls.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"This is iron uptake in a placental cell line, not direct transplacental zinc flux or an in vivo fetal iron requirement for dietary zinc.","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":"Homo sapiens","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"ZIP8 contributed to iron entry in a human placental cell model.","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":"BeWo placental cell line","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"trigger_kind","value_text":"machinery_impairment","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null}],"evidence":[{"id":"4af7df23-0b8b-511d-9bb7-a82536cce784","evidence_kind":"source_excerpt","locator":"Lines 466-477","start_line":466,"end_line":477,"excerpt":"### zinc-trans-zip8-placental-iron\nSuppressing endogenous human ZIP8 in BeWo placental cells reduced iron uptake by approximately 40%.\nCondition category: machinery_impairment\nnutrient_topic: Zinc research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: ZIP8 contributed to iron entry in a human placental cell model.\norganism: Homo sapiens\ntissue_or_cell_type: BeWo placental cell line\nexperimental_model: ZIP8 suppression in BeWo trophoblast-derived cells\nlimitations: This is iron uptake in a placental cell line, not direct transplacental zinc flux or an in vivo fetal iron requirement for dietary zinc.\nexposure: Endogenous ZIP8 knockdown compared with controls.\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":"ZIP8 suppression in BeWo trophoblast-derived cells","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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