{"id":"085f1625-9259-5ecc-9a72-f78d320a39ba","stable_key":"0ad8610d-d575-5870-b7cd-763a9f750783:copper-rat-atp7a-heph-compensation","predicate":"knockdown_increases","statement":"Rat Atp7a knockdown increased hephaestin expression more than tenfold and increased ferroxidase activity, even though net iron uptake and efflux fell.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"86b764fb-c982-51df-8534-3c1c8e53f074","mechanism_event_label":"Compensatory enzyme increases did not repair the overall transport chain.","subject":{"id":"4163dde7-c72e-52c0-b7eb-ff2b3998271f","slug":"rat-atp7a","display_name":"Rat copper-transporting ATPase Atp7a","entity_type_key":"protein"},"object":{"id":"6cef9da6-9a24-5f13-a48a-09614c6e714b","slug":"rat-heph","display_name":"Rat hephaestin Heph","entity_type_key":"protein"},"evidence_count":1,"mechanism_event":{"id":"86b764fb-c982-51df-8534-3c1c8e53f074","stable_key":"0ad8610d-d575-5870-b7cd-763a9f750783:copper-rat-atp7a-heph-compensation-event","event_type":"biochemical_relationship","label":"Compensatory enzyme increases did not repair the overall transport chain.","description":"Rat Atp7a knockdown increased hephaestin expression more than tenfold and increased ferroxidase activity, even though net iron uptake and efflux fell.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"d8626234-45e7-57a4-b88b-4dc7c9c84c08","slug":"intestinal-cell-iron-flux","display_name":"Iron uptake and efflux in cultured intestinal epithelia","entity_type_key":"cellular_process"},"role":"impaired overall outcome","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"4163dde7-c72e-52c0-b7eb-ff2b3998271f","slug":"rat-atp7a","display_name":"Rat copper-transporting ATPase Atp7a","entity_type_key":"protein"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"6cef9da6-9a24-5f13-a48a-09614c6e714b","slug":"rat-heph","display_name":"Rat hephaestin Heph","entity_type_key":"protein"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""}]},"contexts":[{"dimension":"evidence_span","value_text":"{\"source_cache\": \"artifacts/copper-research/27714044.abstract.txt\", \"locator\": \"Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"5e8791edb75475ba74e95cddc330c06512ef3b9c02a0c5a6b203327c047dff37\", \"start_char\": 0, \"end_char\": 1780, \"text_sha256\": \"5e8791edb75475ba74e95cddc330c06512ef3b9c02a0c5a6b203327c047dff37\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"ATP7A knockdown in differentiated intestinal cell cultures","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"ATP7A knockdown and radiolabeled iron transport","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Reductionist cell models; increased enzyme activity did not guarantee increased net iron flux. Molecular expression details were measured in the rat line.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Copper research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"copper","display_name":"Copper","entity_type_key":"nutrient_element"}},{"dimension":"organism","value_text":"Rat","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"Compensatory enzyme increases did not repair the overall transport chain.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[copper-p27714044] Knockdown of copper-transporting ATPase 1 (Atp7a) impairs iron flux in fully-differentiated rat (IEC-6) and human (Caco-2) intestinal epithelial cells. (2016). https://pubmed.ncbi.nlm.nih.gov/27714044/ DOI: 10.1039/c6mt00126b","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"IEC-6 cells","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"3ed844f5-f572-5b07-b58b-7ed69a690ee2","evidence_kind":"source_excerpt","locator":"Lines 910-921","start_line":910,"end_line":921,"excerpt":"### copper-rat-atp7a-heph-compensation\nRat Atp7a knockdown increased hephaestin expression more than tenfold and increased ferroxidase activity, even though net iron uptake and efflux fell.\nCondition category: normal\nnutrient_topic: Copper research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: Compensatory enzyme increases did not repair the overall transport chain.\norganism: Rat\ntissue_or_cell_type: IEC-6 cells\nexperimental_model: ATP7A knockdown in differentiated intestinal cell cultures\nlimitations: Reductionist cell models; increased enzyme activity did not guarantee increased net iron flux. Molecular expression details were measured in the rat line.\nexposure: ATP7A knockdown and radiolabeled iron transport\nevidence_span: {\"source_cache\": \"artifacts/copper-research/27714044.abstract.txt\", \"locator\": \"Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"5e8791edb75475ba74e95cddc330c06512ef3b9c02a0c5a6b203327c047dff37\", \"start_char\": 0, \"end_char\": 1780, \"text_sha256\": \"5e8791edb75475ba74e95cddc330c06512ef3b9c02a0c5a6b203327c047dff37\"}\n[copper-p27714044] Knockdown of copper-transporting ATPase 1 (Atp7a) impairs iron flux in fully-differentiated rat (IEC-6) and human (Caco-2) intestinal epithelial cells. (2016). https://pubmed.ncbi.nlm.nih.gov/27714044/ DOI: 10.1039/c6mt00126b","model_system":"ATP7A knockdown in differentiated intestinal cell cultures","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [copper-p27714044] Knockdown of copper-transporting ATPase 1 (Atp7a) impairs iron flux in fully-differentiated rat (IEC-6) and human (Caco-2) intestinal epithelial cells. (2016). https://pubmed.ncbi.nlm.nih.gov/27714044/ DOI: 10.1039/c6mt00126b","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"9afba495-cbdc-51aa-998e-70a930dba3be","stable_key":"import-0ad8610d-d575-5870-b7cd-763a9f750783","title":"Copper: transport, cuproenzymes, deficiency, excess 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. Not publisher full text.","file_path":"","sha256":"84b0f62b2dae6835fa26902be87625c003c6c707492d3007e8f9d15420669008","revision_id":"d7e35b8b-3f77-56d9-90b5-5f542c63f321","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}