{"id":"019e4453-e692-5689-889f-75ab5146e71c","stable_key":"6b15b2de-9ce9-5b6f-ab8b-3c7dbb4c15c7:stevia-cftr-degradation","predicate":"reduces_expression_of","statement":"Steviol at 100 micromolar for 24 hours reduced CFTR protein expression in MDCK cells; MG-132 abolished the expression effect.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"negative","is_public":true,"mechanism_event_id":"cd4f285a-2736-5108-95b9-46065c886b1e","mechanism_event_label":"A longer exposure changes protein abundance as well as acute channel activity.","subject":{"id":"8ba32fe6-183f-5cd5-b386-02e6440e78a0","slug":"steviol","display_name":"Steviol","entity_type_key":"small_molecule"},"object":{"id":"2b04e6b2-6fd0-5a0d-8f08-565c7f1e61cc","slug":"dog-cftr","display_name":"Canine cystic fibrosis transmembrane conductance regulator / CFTR","entity_type_key":"protein"},"evidence_count":1,"mechanism_event":{"id":"cd4f285a-2736-5108-95b9-46065c886b1e","stable_key":"6b15b2de-9ce9-5b6f-ab8b-3c7dbb4c15c7:stevia-cftr-degradation-event","event_type":"observed_relationship","label":"A longer exposure changes protein abundance as well as acute channel activity.","description":"Steviol at 100 micromolar for 24 hours reduced CFTR protein expression in MDCK cells; MG-132 abolished the expression effect.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"8ba32fe6-183f-5cd5-b386-02e6440e78a0","slug":"steviol","display_name":"Steviol","entity_type_key":"small_molecule"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"2b04e6b2-6fd0-5a0d-8f08-565c7f1e61cc","slug":"dog-cftr","display_name":"Canine cystic fibrosis transmembrane conductance regulator / CFTR","entity_type_key":"protein"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"c78086c3-7657-589b-b353-1691df2d9f8f","slug":"stevia","display_name":"Stevia","entity_type_key":"small_molecule"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""}]},"contexts":[{"dimension":"evidence_access","value_text":"Primary abstract","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Canine MDCK culture with proteasome-inhibitor intervention.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Proteasomal involvement is supported; a specific ubiquitination enzyme or human treatment effect is not established.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Stevia collection; species, compartment, exposure, co-substrates and manipulation remain explicit.","comparator":null,"unit":null,"notes":"","entity":{"slug":"stevia","display_name":"Stevia","entity_type_key":"small_molecule"}},{"dimension":"plain_language","value_text":"A longer exposure changes protein abundance as well as acute channel activity.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"Steviol reduces MDCK Cyst formation and growth by inhibiting CFTR channel activity and promoting proteasome-mediated CFTR degradation. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23536832/ · DOI 10.1371/journal.pone.0058871","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"89b409f1-77bd-56ce-a30c-60bbeb9d6634","evidence_kind":"source_excerpt","locator":"Lines 306-312","start_line":306,"end_line":312,"excerpt":"## stevia-cftr-degradation\nA longer exposure changes protein abundance as well as acute channel activity.\nSteviol at 100 micromolar for 24 hours reduced CFTR protein expression in MDCK cells; MG-132 abolished the expression effect.\nModel: Canine MDCK culture with proteasome-inhibitor intervention.\nLimitations: Proteasomal involvement is supported; a specific ubiquitination enzyme or human treatment effect is not established.\nEvidence access: Primary abstract\nSteviol reduces MDCK Cyst formation and growth by inhibiting CFTR channel activity and promoting proteasome-mediated CFTR degradation. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23536832/ · DOI 10.1371/journal.pone.0058871","model_system":"Canine MDCK culture with proteasome-inhibitor intervention.","directness":"reported_statement","verification_status":"source_derived_draft","notes":"Original curation paraphrase; evidence access and experimental limitations specified.","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"295304c9-609c-5b05-a18f-a00ab7b965ed","stable_key":"import-6b15b2de-9ce9-5b6f-ab8b-3c7dbb4c15c7","title":"Stevia: glycoside metabolism, taste, ion channels and cross-nutrient mechanisms (2026-09-19)","document_type":"imported_text","citation_label":"AI-assisted research curation; primary references, access levels and experimental limitations individually identified. 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