{"id":"cb1cec86-74f1-5898-9eb5-a571115c2be4","stable_key":"e0ea2d6a-7429-5e9f-b774-41e5e3288da3:ver-liver-gpx4-e-withdrawal","predicate":"predisposes-to","statement":"After six weeks on vitamin E-enriched diets, switching liver-specific Gpx4-null mice to vitamin E-deficient diet caused extensive hepatocellular necrosis and loss of the prior survival rescue; control genotypes survived the monitored 78 days after withdrawal.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"positive","is_public":true,"mechanism_event_id":"87baa99a-86c9-5cbe-a433-2cc66787dd8a","mechanism_event_label":"The rescued mice remained dependent on continued vitamin E supply.","subject":{"id":"0f74f458-e4e0-512e-814d-2ec3de0b0be8","slug":"gpx4-hepatocyte-loss","display_name":"Hepatocyte-directed GPX4 loss","entity_type_key":"protein_state"},"object":{"id":"79e37986-63fa-5141-8427-1df1888eda8b","slug":"hepatocyte-necrosis","display_name":"Hepatocyte necrosis","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"87baa99a-86c9-5cbe-a433-2cc66787dd8a","stable_key":"e0ea2d6a-7429-5e9f-b774-41e5e3288da3:ver-liver-gpx4-e-withdrawal-event","event_type":"biochemical_relationship","label":"The rescued mice remained dependent on continued vitamin E supply.","description":"After six weeks on vitamin E-enriched diets, switching liver-specific Gpx4-null mice to vitamin E-deficient diet caused extensive hepatocellular necrosis and loss of the prior survival rescue; control genotypes survived the monitored 78 days after withdrawal.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"40a6525a-76b8-576e-b73d-1e11aecf5f8d","slug":"alpha-tocopherol","display_name":"Alpha-tocopherol","entity_type_key":"small_molecule"},"role":"withdrawn nutrient","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"e9bb13ee-f238-51e6-9101-78ddfd11465c","slug":"gpx4","display_name":"GPX4","entity_type_key":"protein"},"role":"deleted enzyme","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"0f74f458-e4e0-512e-814d-2ec3de0b0be8","slug":"gpx4-hepatocyte-loss","display_name":"Hepatocyte-directed GPX4 loss","entity_type_key":"protein_state"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"79e37986-63fa-5141-8427-1df1888eda8b","slug":"hepatocyte-necrosis","display_name":"Hepatocyte necrosis","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""}]},"contexts":[{"dimension":"availability_state","value_text":"nutrient_deficiency","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":"evidence_location","value_text":"Figures 4–5","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Diet withdrawal after developmental rescue","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"E-enriched diet through 6 weeks; subsequent E withdrawal; necrosis examined after 3 weeks.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Alb-Cre Gpx4 loss is machinery impairment, not selenium deficiency; mouse survival rescue does not establish human substitutability.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Vitamin E research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"vitamin-e","display_name":"Vitamin E","entity_type_key":"chemical_species"}},{"dimension":"organism","value_text":"Mus musculus","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"The rescued mice remained dependent on continued vitamin E supply.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[ver-carlson2016] Glutathione peroxidase 4 and vitamin E cooperatively prevent hepatocellular degeneration. (2016). https://pubmed.ncbi.nlm.nih.gov/27262435/ DOI: 10.1016/j.redox.2016.05.003","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Liver","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"trigger_kind","value_text":"nutrient_deficiency","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null}],"evidence":[{"id":"be955a26-d374-5ab2-88c3-db80215bc3af","evidence_kind":"source_excerpt","locator":"Lines 620-632","start_line":620,"end_line":632,"excerpt":"### ver-liver-gpx4-e-withdrawal\nAfter six weeks on vitamin E-enriched diets, switching liver-specific Gpx4-null mice to vitamin E-deficient diet caused extensive hepatocellular necrosis and loss of the prior survival rescue; control genotypes survived the monitored 78 days after withdrawal.\nCondition category: nutrient_deficiency\nnutrient_topic: Vitamin E research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: The rescued mice remained dependent on continued vitamin E supply.\norganism: Mus musculus\ntissue_or_cell_type: Liver\nexperimental_model: Diet withdrawal after developmental rescue\nlimitations: Alb-Cre Gpx4 loss is machinery impairment, not selenium deficiency; mouse survival rescue does not establish human substitutability.\nexposure: E-enriched diet through 6 weeks; subsequent E withdrawal; necrosis examined after 3 weeks.\ncross_nutrient: true\nevidence_location: Figures 4–5\n[ver-carlson2016] Glutathione peroxidase 4 and vitamin E cooperatively prevent hepatocellular degeneration. 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