{"id":"1f51c288-65fa-5731-a3bc-33b99d64bfa9","stable_key":"availability:selenop-tissue-selective-delivery:2","predicate":"supports","statement":"ApoER2/LRP8-mediated SELENOP uptake contributes to preferential brain and testis selenium retention during dietary restriction in experimental models.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"source_reported: Animal model and biochemical transport biology; source-derived unverified synthesis.","direction":"positive","is_public":true,"mechanism_event_id":"7196f9c1-c9c7-58bf-acc9-8cdcdc1f236b","mechanism_event_label":"ApoER2/LRP8-mediated SELENOP uptake contributes to preferential brain and testis selenium retention during dietary restriction in experimental models.","subject":{"id":"f47ee853-9252-56f4-8e2a-48ede17ed3a3","slug":"lrp8","display_name":"ApoER2 / LRP8","entity_type_key":"protein"},"object":{"id":"c9b77137-454d-5da3-aec0-852370f27272","slug":"selenop-tissue-uptake","display_name":"SELENOP uptake in brain and testis","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"7196f9c1-c9c7-58bf-acc9-8cdcdc1f236b","stable_key":"availability:selenop-tissue-selective-delivery:2","event_type":"availability_dependent_change","label":"ApoER2/LRP8-mediated SELENOP uptake contributes to preferential brain and testis selenium retention during dietary restriction in experimental models.","description":"Dietary selenium availability declines. Tissue-selective distribution, largely from experimental models; relative retention differs from absolute protection.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"f47ee853-9252-56f4-8e2a-48ede17ed3a3","slug":"lrp8","display_name":"ApoER2 / LRP8","entity_type_key":"protein"},"role":"condition_input","stoichiometry":null,"state_label":"Dietary selenium availability declines.","sequence_order":0,"notes":""},{"entity":{"id":"c9b77137-454d-5da3-aec0-852370f27272","slug":"selenop-tissue-uptake","display_name":"SELENOP uptake in brain and testis","entity_type_key":"cellular_process"},"role":"affected_component","stoichiometry":null,"state_label":"Dietary selenium availability declines.","sequence_order":1,"notes":""}]},"contexts":[{"dimension":"availability_state","value_text":"Dietary selenium availability declines.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_scope","value_text":"Tissue-selective distribution, largely from experimental models; relative retention differs from absolute protection.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"There is no fixed human organ sacrifice sequence. Low circulating SELENOP can also reflect inflammation, and receptor disruption is a distinct machinery state.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"trigger_kind","value_text":"nutrient_deficiency","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"2b50d69f-8c48-5254-b167-87528db781a5","evidence_kind":"source_passage","locator":"lines 129-139","start_line":129,"end_line":139,"excerpt":"2.2 Tissue hierarchy\n\nSelenium distribution is also tissue-selective. Brain and testis can retain selenium relatively well during dietary restriction, in part through SELENOP receptor biology. ApoER2/LRP8 is important for SELENOP uptake in the brain and testis; megalin/LRP2 contributes to renal handling of filtered selenium-containing proteins.\n\nA safer conceptual map is:\n\nLESS RETENTION / EARLIER FALL                STRONGER RETENTION IN MANY MODELS\nplasma, liver, skeletal muscle   ───────────────►   brain, testis\n                         tissue- and model-dependent\n\nThe liver is a major producer of circulating SELENOP. Severe deficiency can produce cardiac and skeletal-muscle pathology, while the brain may be relatively protected in some experimental models. That does not establish one fixed organ-by-organ sacrifice order in humans.","model_system":"Supplied reference; verify the primary study and experimental context.","directness":"reported_statement","verification_status":"source_derived_draft","notes":"","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"c788c19c-884c-5233-92b1-0bd063d87741","stable_key":"deficiency","title":"Selenium deficiency: a mechanism-first reference","document_type":"user_supplied_reference","citation_label":"Supplied selenium deficiency reference","file_path":"X:\\metabolic-ledger\\source_material\\selenium-deficiency-reference.md","sha256":"a3f14bc3fa24c595dda830664523090a7b5bfa76e9dcf517f42f62212ceb767e","revision_id":"f8f97804-c1fb-56df-9c06-c02e36e2a5b8","review_status":"unverified_draft","notes":"Preserved verbatim. Reported study types are source labels, not independent verification."}}],"relations":[],"conflicts":[],"corrections":[],"research":null}