{"id":"e6adee32-20c1-5e37-84f3-ed8f37d9ca3f","stable_key":"6d38d43e-01e4-5641-93be-65654271e242:zinc-trans-renal-zip8-manganese","predicate":"supports","statement":"ZIP8-specific siRNA reduced manganese uptake from the apical side of polarized mouse proximal-tubule cells.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"positive","is_public":true,"mechanism_event_id":"8cf18a6e-6d2d-59d8-8c64-65322e29ece1","mechanism_event_label":"A transporter known to handle zinc also helped kidney-derived cells take up manganese from their lumen-facing side.","subject":{"id":"b014fa2d-844c-58c5-bda9-1e31fae2c73c","slug":"mouse-slc39a8","display_name":"Mouse ZIP8 (Slc39a8)","entity_type_key":"protein"},"object":{"id":"ef134340-d6ae-5c8f-8b76-303bcc66760a","slug":"cellular-manganese-uptake","display_name":"Cellular manganese uptake","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"8cf18a6e-6d2d-59d8-8c64-65322e29ece1","stable_key":"6d38d43e-01e4-5641-93be-65654271e242:zinc-trans-renal-zip8-manganese-event","event_type":"biochemical_relationship","label":"A transporter known to handle zinc also helped kidney-derived cells take up manganese from their lumen-facing side.","description":"ZIP8-specific siRNA reduced manganese uptake from the apical side of polarized mouse proximal-tubule cells.","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":"49c806c2-7041-5020-8b3b-fa04ffa122ac","slug":"zinc-ion","display_name":"Zinc(II) ion","entity_type_key":"ion"},"role":"transporter_family_context_only","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"b014fa2d-844c-58c5-bda9-1e31fae2c73c","slug":"mouse-slc39a8","display_name":"Mouse ZIP8 (Slc39a8)","entity_type_key":"protein"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"ef134340-d6ae-5c8f-8b76-303bcc66760a","slug":"cellular-manganese-uptake","display_name":"Cellular manganese 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":"Polarized proximal-tubule culture with separately accessible apical and basolateral compartments","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"ZIP8 siRNA versus controls during apical manganese exposure.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"This is manganese uptake, not direct proof of zinc reabsorption by ZIP8; ZIP14 and DMT1 knockdowns also affected uptake in the paper.","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":"Mus musculus","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"A transporter known to handle zinc also helped kidney-derived cells take up manganese from their lumen-facing side.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[zinc-trans-22534978] Roles of ZIP8, ZIP14, and DMT1 in transport of cadmium and manganese in mouse kidney proximal tubule cells. (2012). https://pubmed.ncbi.nlm.nih.gov/22534978/ DOI: 10.1039/c2mt20024d","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Mouse proximal-tubule epithelial cells","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":"c3f32e08-18aa-51f9-ab72-d409d4ed61d0","evidence_kind":"source_excerpt","locator":"Lines 531-542","start_line":531,"end_line":542,"excerpt":"### zinc-trans-renal-zip8-manganese\nZIP8-specific siRNA reduced manganese uptake from the apical side of polarized mouse proximal-tubule cells.\nCondition category: machinery_impairment\nnutrient_topic: Zinc research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: A transporter known to handle zinc also helped kidney-derived cells take up manganese from their lumen-facing side.\norganism: Mus musculus\ntissue_or_cell_type: Mouse proximal-tubule epithelial cells\nexperimental_model: Polarized proximal-tubule culture with separately accessible apical and basolateral compartments\nlimitations: This is manganese uptake, not direct proof of zinc reabsorption by ZIP8; ZIP14 and DMT1 knockdowns also affected uptake in the paper.\nexposure: ZIP8 siRNA versus controls during apical manganese exposure.\ncross_nutrient: true\n[zinc-trans-22534978] Roles of ZIP8, ZIP14, and DMT1 in transport of cadmium and manganese in mouse kidney proximal tubule cells. 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