{"id":"206bada7-5fb4-561b-b4fb-a26093d1a3ae","stable_key":"6d38d43e-01e4-5641-93be-65654271e242:zn-sig-zip7-zinc-no-rescue","predicate":"supplementation_failed_to_suppress","statement":"Adding 1 µM ZnSO4 did not suppress ER-stress gene induction in Zip7-deficient intestinal organoids assessed 48 hours after induction of deletion; the study also observed no rescue in fibroblasts, while restored ZIP7 expression rescued their stress response.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"neutral","is_public":true,"mechanism_event_id":"5e82306b-18c5-5da1-918d-34112d7fbebf","mechanism_event_label":"More available zinc did not substitute for the missing distribution machinery.","subject":{"id":"0429f0ff-c033-514b-9a4f-6f0f83268095","slug":"zinc","display_name":"Zinc","entity_type_key":"nutrient_element"},"object":{"id":"b552beea-0f46-568a-a393-8c398e1b8c00","slug":"intestinal-crypt-er-stress","display_name":"Intestinal crypt endoplasmic-reticulum stress","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"5e82306b-18c5-5da1-918d-34112d7fbebf","stable_key":"6d38d43e-01e4-5641-93be-65654271e242:zn-sig-zip7-zinc-no-rescue-event","event_type":"biochemical_relationship","label":"More available zinc did not substitute for the missing distribution machinery.","description":"Adding 1 µM ZnSO4 did not suppress ER-stress gene induction in Zip7-deficient intestinal organoids assessed 48 hours after induction of deletion; the study also observed no rescue in fibroblasts, while restored ZIP7 expression rescued their stress response.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"22580582-85ca-5c49-a512-fc7f90cee70a","slug":"mouse-slc39a7","display_name":"Mouse ZIP7 / Slc39a7","entity_type_key":"protein"},"role":"affected_transporter","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"9f823444-e2dd-5e16-9440-1bf2f62e8bdf","slug":"zinc-sulfate","display_name":"Zinc sulfate","entity_type_key":"chemical_species"},"role":"tested_preparation","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"0429f0ff-c033-514b-9a4f-6f0f83268095","slug":"zinc","display_name":"Zinc","entity_type_key":"nutrient_element"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"b552beea-0f46-568a-a393-8c398e1b8c00","slug":"intestinal-crypt-er-stress","display_name":"Intestinal crypt endoplasmic-reticulum stress","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":"Mouse ZIP7 / Slc39a7 (affected_transporter)","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"evidence_span","value_text":"{\"source_cache\": \"artifacts/zinc-signaling-sources/27736879.txt\", \"locator\": \"Results: Zip7 deletion activates ER stress; Figure 4, Figure 5 and supplemental Figure S8\", \"file_sha256\": \"4771f8b4a2b4e332b10bd2a5abef6f538cc38f4c85916b44ddab9f15679ed621\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Conditional intestinal Zip7-deficient mice and organoids","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Supplemental Figure S8: 1 µM ZnSO4; intestinal organoids assessed 48 hours after the study-induced Zip7 deletion. The fibroblast comparison also used 1 µM ZnSO4. This exposure did not suppress the measured ER-stress gene induction.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Cell lineage and tissue context matter. Supplementation failing to rescue a transporter defect is not evidence that ordinary dietary zinc replacement fails.","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":"More available zinc did not substitute for the missing distribution machinery.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[zn-sig-27736879] Zinc Transporter SLC39A7/ZIP7 Promotes Intestinal Epithelial Self-Renewal by Resolving ER Stress. (2016). https://pubmed.ncbi.nlm.nih.gov/27736879/ DOI: 10.1371/journal.pgen.1006349","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Intestinal crypts, progenitor cells and organoids","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":"d511177b-b325-54df-b4f7-b52fb0cf3370","evidence_kind":"source_excerpt","locator":"Lines 1139-1151","start_line":1139,"end_line":1151,"excerpt":"### zn-sig-zip7-zinc-no-rescue\nAdding 1 µM ZnSO4 did not suppress ER-stress gene induction in Zip7-deficient intestinal organoids assessed 48 hours after induction of deletion; the study also observed no rescue in fibroblasts, while restored ZIP7 expression rescued their stress response.\nCondition category: machinery_impairment\nnutrient_topic: Zinc research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: More available zinc did not substitute for the missing distribution machinery.\norganism: Mus musculus\ntissue_or_cell_type: Intestinal crypts, progenitor cells and organoids\nexperimental_model: Conditional intestinal Zip7-deficient mice and organoids\nlimitations: Cell lineage and tissue context matter. Supplementation failing to rescue a transporter defect is not evidence that ordinary dietary zinc replacement fails.\nexposure: Supplemental Figure S8: 1 µM ZnSO4; intestinal organoids assessed 48 hours after the study-induced Zip7 deletion. The fibroblast comparison also used 1 µM ZnSO4. This exposure did not suppress the measured ER-stress gene induction.\ncross_nutrient: Mouse ZIP7 / Slc39a7 (affected_transporter)\nevidence_span: {\"source_cache\": \"artifacts/zinc-signaling-sources/27736879.txt\", \"locator\": \"Results: Zip7 deletion activates ER stress; Figure 4, Figure 5 and supplemental Figure S8\", \"file_sha256\": \"4771f8b4a2b4e332b10bd2a5abef6f538cc38f4c85916b44ddab9f15679ed621\"}\n[zn-sig-27736879] Zinc Transporter SLC39A7/ZIP7 Promotes Intestinal Epithelial Self-Renewal by Resolving ER Stress. (2016). https://pubmed.ncbi.nlm.nih.gov/27736879/ DOI: 10.1371/journal.pgen.1006349","model_system":"Conditional intestinal Zip7-deficient mice and organoids","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [zn-sig-27736879] Zinc Transporter SLC39A7/ZIP7 Promotes Intestinal Epithelial Self-Renewal by Resolving ER Stress. (2016). https://pubmed.ncbi.nlm.nih.gov/27736879/ DOI: 10.1371/journal.pgen.1006349","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"c5ee0fee-ce5c-58de-905a-10fb0ea0723c","stable_key":"import-6d38d43e-01e4-5641-93be-65654271e242","title":"Zinc: transport, enzyme loading, deficiency and nutrient interactions (2026-09-17)","document_type":"imported_text","citation_label":"AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text.","file_path":"","sha256":"2e731dd54477ec1254e97df3323e1208d38f1375effed19252e71ab4f600d13a","revision_id":"c72258b9-ac09-5408-9d44-a921ad1f96a3","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}