{"id":"bedae907-6e82-5298-a29e-d35abfd17a04","stable_key":"be889add-cec8-500b-be89-676431432a70:mn-trans-hepatic-zip8-overexpression-bile-mn","predicate":"decreases","statement":"Liver-directed human ZIP8 overexpression decreased bile manganese in mice.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"negative","is_public":true,"mechanism_event_id":"6df0f3a5-904b-5a1f-8fd0-dbd88fb464d6","mechanism_event_label":"More liver ZIP8 left less manganese in bile.","subject":{"id":"ce4864c9-d5fa-501e-88c0-c9ed3f9aa762","slug":"mouse-hepatic-human-zip8-overexpression","display_name":"Mouse liver human ZIP8 overexpression state","entity_type_key":"protein_state"},"object":{"id":"718ade6f-5b2c-598b-b62a-2e31d453354a","slug":"biliary-manganese-concentration","display_name":"Biliary manganese concentration","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"6df0f3a5-904b-5a1f-8fd0-dbd88fb464d6","stable_key":"be889add-cec8-500b-be89-676431432a70:mn-trans-hepatic-zip8-overexpression-bile-mn-event","event_type":"biochemical_relationship","label":"More liver ZIP8 left less manganese in bile.","description":"Liver-directed human ZIP8 overexpression decreased bile manganese in mice.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"a8082b11-c484-5792-bb81-48e8e699cbe4","slug":"manganese-ion","display_name":"Mn2+","entity_type_key":"ion"},"role":"transported_substrate","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"059eea33-6e24-58ca-970f-014e2e65df77","slug":"slc39a8","display_name":"Human ZIP8 (SLC39A8)","entity_type_key":"protein"},"role":"overexpressed_human_transporter","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"ce4864c9-d5fa-501e-88c0-c9ed3f9aa762","slug":"mouse-hepatic-human-zip8-overexpression","display_name":"Mouse liver human ZIP8 overexpression state","entity_type_key":"protein_state"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"718ade6f-5b2c-598b-b62a-2e31d453354a","slug":"biliary-manganese-concentration","display_name":"Biliary manganese concentration","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""}]},"contexts":[{"dimension":"cross_nutrient","value_text":"false","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Mouse liver-specific Slc39a8 deletion and liver-directed human ZIP8 overexpression","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Liver-specific AAV-human-ZIP8 versus study controls.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Bile concentration is distinct from measured excretion flux.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Manganese research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"manganese","display_name":"Manganese","entity_type_key":"nutrient_element"}},{"dimension":"organism","value_text":"Mus musculus with human ZIP8 transgene","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"More liver ZIP8 left less manganese in bile.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[mn-trans-28481222] Hepatic metal ion transporter ZIP8 regulates manganese homeostasis and manganese-dependent enzyme activity. (2017). https://pubmed.ncbi.nlm.nih.gov/28481222/ DOI: 10.1172/jci90896","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Liver, bile and measured extrahepatic tissues","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"29060a7e-cad7-5f83-8599-606abff2f6d8","evidence_kind":"source_excerpt","locator":"Lines 175-186","start_line":175,"end_line":186,"excerpt":"### mn-trans-hepatic-zip8-overexpression-bile-mn\nLiver-directed human ZIP8 overexpression decreased bile manganese in mice.\nCondition category: normal\nnutrient_topic: Manganese research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: More liver ZIP8 left less manganese in bile.\norganism: Mus musculus with human ZIP8 transgene\ntissue_or_cell_type: Liver, bile and measured extrahepatic tissues\nexperimental_model: Mouse liver-specific Slc39a8 deletion and liver-directed human ZIP8 overexpression\nlimitations: Bile concentration is distinct from measured excretion flux.\nexposure: Liver-specific AAV-human-ZIP8 versus study controls.\ncross_nutrient: false\n[mn-trans-28481222] Hepatic metal ion transporter ZIP8 regulates manganese homeostasis and manganese-dependent enzyme activity. 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