{"id":"82b96fdd-eb4d-5fd8-a3ef-005d239d421a","stable_key":"584c58f5-ab9f-53f3-97a9-55783db943b0:tryptophan-indoxyl-cell-uptake","predicate":"induces_after_transport","statement":"Indoxyl sulfate entered human HK-2 proximal-tubule cells through organic-anion transport and induced Nrf2 activation consistent with intracellular oxidative stress.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"22820f04-0b9c-5af9-88f4-6d9e3a4d5c6d","mechanism_event_label":"Transport into kidney cells can expose them to a downstream metabolite.","subject":{"id":"6cfa468b-cd28-52fe-bea7-34433868935e","slug":"indoxyl-sulfate","display_name":"Indoxyl sulfate","entity_type_key":"small_molecule"},"object":{"id":"a7bd7506-b512-504d-a8f4-b1bc3037027c","slug":"human-hk2-indoxyl-response","display_name":"Human HK-2 cellular indoxyl-sulfate uptake and Nrf2 response","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"22820f04-0b9c-5af9-88f4-6d9e3a4d5c6d","stable_key":"584c58f5-ab9f-53f3-97a9-55783db943b0:tryptophan-indoxyl-cell-uptake-event","event_type":"observed_relationship","label":"Transport into kidney cells can expose them to a downstream metabolite.","description":"Indoxyl sulfate entered human HK-2 proximal-tubule cells through organic-anion transport and induced Nrf2 activation consistent with intracellular oxidative stress.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"6cfa468b-cd28-52fe-bea7-34433868935e","slug":"indoxyl-sulfate","display_name":"Indoxyl sulfate","entity_type_key":"small_molecule"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"a7bd7506-b512-504d-a8f4-b1bc3037027c","slug":"human-hk2-indoxyl-response","display_name":"Human HK-2 cellular indoxyl-sulfate uptake and Nrf2 response","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"769339cb-213b-559e-acc0-07ed00368b94","slug":"l-tryptophan","display_name":"L-Tryptophan","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":"Human proximal-tubule-derived HK-2 cell experiments.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Accessed abstract does not resolve each transporter isoform in this cell assay; Nrf2 activation is not itself proof of clinical renal injury.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Tryptophan collection; molecular form, preparation, species, exposure and manipulation remain explicit.","comparator":null,"unit":null,"notes":"","entity":{"slug":"l-tryptophan","display_name":"L-Tryptophan","entity_type_key":"small_molecule"}},{"dimension":"plain_language","value_text":"Transport into kidney cells can expose them to a downstream metabolite.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"Hepatic sulfotransferase as a nephropreventing target by suppression of the uremic toxin indoxyl sulfate accumulation in ischemic acute kidney injury. · 2014 · https://pubmed.ncbi.nlm.nih.gov/24958931/ · DOI 10.1093/toxsci/kfu119","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"ac563148-3f26-5283-920f-81a342782cb0","evidence_kind":"source_excerpt","locator":"Lines 602-608","start_line":602,"end_line":608,"excerpt":"## tryptophan-indoxyl-cell-uptake\nTransport into kidney cells can expose them to a downstream metabolite.\nIndoxyl sulfate entered human HK-2 proximal-tubule cells through organic-anion transport and induced Nrf2 activation consistent with intracellular oxidative stress.\nModel: Human proximal-tubule-derived HK-2 cell experiments.\nLimitations: Accessed abstract does not resolve each transporter isoform in this cell assay; Nrf2 activation is not itself proof of clinical renal injury.\nEvidence access: Primary abstract\nHepatic sulfotransferase as a nephropreventing target by suppression of the uremic toxin indoxyl sulfate accumulation in ischemic acute kidney injury. · 2014 · https://pubmed.ncbi.nlm.nih.gov/24958931/ · DOI 10.1093/toxsci/kfu119","model_system":"Human proximal-tubule-derived HK-2 cell experiments.","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":"73f9d3e7-fdc9-5418-8f3c-f4ef145f6efa","stable_key":"import-584c58f5-ab9f-53f3-97a9-55783db943b0","title":"Tryptophan: transport, protein synthesis, neuroactive metabolites, NAD and microbial pathways (2026-09-19)","document_type":"imported_text","citation_label":"AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text.","file_path":"","sha256":"7dfd20063b91900cb5c6ad675e3e675b7e25ef0fb8304eabac6f263cc5518284","revision_id":"bfafd789-fdf5-521f-bd28-c662e01ec1ea","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}