{"id":"5635aaba-e621-5bbf-b955-d485bbf14537","stable_key":"33bef151-bdc7-5892-aff6-0345ab149739:heat-inactivated-nattokinase-raises-tpa-activity-in-cells","predicate":"increases","statement":"Culture solutions of Bacillus subtilis natto and market nattokinase, deactivated by heating at 121 C for 15 min, raised tissue-plasminogen-activator activity in HeLa cells about 20-fold and 24-fold and in human umbilical vein endothelial cells about 5-fold.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"positive","is_public":true,"mechanism_event_id":"6d894558-103a-549f-b68d-ce8228a4071d","mechanism_event_label":"Culture solutions of Bacillus subtilis natto and market nattokinase, deactivated by heating at 121 C for 15 min, raised tissue-plasminogen-activator activity in HeLa cells about 20-fold and 24-fold an","subject":{"id":"4d4eafa0-9952-5fa2-bb60-74e072c25edb","slug":"heat-inactivated-nattokinase","display_name":"Heat-inactivated nattokinase","entity_type_key":"protein_state"},"object":{"id":"af7cb0f2-868e-51dd-ace8-51882e376238","slug":"plat","display_name":"Human tissue-type plasminogen activator / tPA / PLAT","entity_type_key":"protein"},"evidence_count":1,"mechanism_event":{"id":"6d894558-103a-549f-b68d-ce8228a4071d","stable_key":"33bef151-bdc7-5892-aff6-0345ab149739:heat-inactivated-nattokinase-raises-tpa-activity-in-cells-event","event_type":"biochemical_relationship","label":"Culture solutions of Bacillus subtilis natto and market nattokinase, deactivated by heating at 121 C for 15 min, raised tissue-plasminogen-activator activity in HeLa cells about 20-fold and 24-fold an","description":"HeLa and human umbilical vein endothelial cells","status":"provisional","compartment":null,"participants":[{"entity":{"id":"4d4eafa0-9952-5fa2-bb60-74e072c25edb","slug":"heat-inactivated-nattokinase","display_name":"Heat-inactivated nattokinase","entity_type_key":"protein_state"},"role":"acting component","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"af7cb0f2-868e-51dd-ace8-51882e376238","slug":"plat","display_name":"Human tissue-type plasminogen activator / tPA / PLAT","entity_type_key":"protein"},"role":"component the finding is about","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""}]},"contexts":[{"dimension":"duration","value_text":"Not stated here","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"evidence_access","value_text":"Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Human cells","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Heat-deactivated nattokinase and heat-deactivated B. subtilis natto culture solution","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"The subject here is the heat-inactivated material, not the active protease: the same report shows that heating to 70 C or above destroys the fibrinolytic and amidolytic activity. Cell counts did not change, so the effect is not a viability artefact. This is a regulated cellular response, not proteolytic generation of tPA, and it conflicts in direction with the endothelial result recorded next.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"organism","value_text":"Human cells","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"Culture solutions of Bacillus subtilis natto and market nattokinase, deactivated by heating at 121 C for 15 min, raised tissue-plasminogen-activator activity in HeLa cells about 20-fold and 24-fold and in human umbilical vein endothelial cells about 5-fold.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"Nattokinase-promoted tissue plasminogen activator release from human cells. (2008) https://pubmed.ncbi.nlm.nih.gov/19996631/ DOI: 10.1159/000252817","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"route","value_text":"In vitro","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue","value_text":"HeLa and human umbilical vein endothelial cells","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"e45074ca-2a2b-5f4d-9990-79cc1b28145a","evidence_kind":"source_excerpt","locator":"Lines 433-433","start_line":433,"end_line":433,"excerpt":"Culture solutions of Bacillus subtilis natto and market nattokinase, deactivated by heating at 121 C for 15 min, raised tissue-plasminogen-activator activity in HeLa cells about 20-fold and 24-fold and in human umbilical vein endothelial cells about 5-fold.","model_system":"Human cells","directness":"reported_statement","verification_status":"source_derived_draft","notes":"","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"41cb127c-1c23-53aa-b7d0-5ec7f6fa3c99","stable_key":"import-33bef151-bdc7-5892-aff6-0345ab149739","title":"Nattokinase: what the purified enzyme cleaves, what survives being eaten, and the gap between the two (2026-09-23)","document_type":"imported_text","citation_label":"Original AI-assisted curation built from a supplied entity-first document of 105 entities and 129 claims. Every reference in that document was resolved against live PubMed with its abstract read and its DOI cross-checked on 2026-09-23, and the EFSA novel-food opinion was retrieved and read in full. That check corrected two PMIDs that pointed at unrelated papers, two DOIs, and two papers recorded as carrying no erratum that do carry one; it also reversed three findings the supplied document had stated backwards. Two papers carry a published correction, recorded as such and not as a retraction. Three sources are not indexed in PubMed and are cited by what they have. Laboratory lineages are recorded, so the four papers from one group, the three from another and the two readings of a single applicant dossier cannot be counted as separate lines of support. Study-specific doses, units, populations and limitations retained; activity units are never converted between systems. Not publisher full text.","file_path":"","sha256":"34fc46e0e849d06bfa13cb099a79b50679dd6fd0de8a5a0575326afdde3259c1","revision_id":"efd063e6-e982-5f6e-a4b8-6f2ffe4185ce","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[{"id":"e0314277-7470-54a9-97b8-87c73756706b","title":"Nattokinase raises tPA in one endothelial study and lowers it in another","kind":"contradiction","status":"open","why":"Yatagai 2008 raised tissue-plasminogen-activator activity about five-fold in human umbilical vein endothelial cells using heat-deactivated material, while Ji 2014 found nattokinase reducing adrenaline-stimulated tPA secretion from the same cell type. The two differ in whether the enzyme was catalytically active and in whether the cells were stimulated, and either difference could explain the sign. Both readings are load-bearing: the first is the only evidence that inactivated material has a cellular effect, and the second is part of the mechanism proposed for cerebral protection.","resolution":"Unresolved. A single experiment comparing active and heat-inactivated enzyme in stimulated and unstimulated endothelium would settle it.","created_at":"2026-09-23 07:55:19","record_type":"conflict","display_label":"Recorded conflict","record_url":"/conflicts/e0314277-7470-54a9-97b8-87c73756706b","sides":[{"conflict_id":"e0314277-7470-54a9-97b8-87c73756706b","ordinal":0,"label":"Heat-deactivated nattokinase raised tPA activity in HeLa and endothelial cells","revision_id":"efd063e6-e982-5f6e-a4b8-6f2ffe4185ce","start_line":433,"end_line":433,"quote":"Culture solutions of Bacillus subtilis natto and market nattokinase, deactivated by heating at 121 C for 15 min, raised tissue-plasminogen-activator activity in HeLa cells about 20-fold and 24-fold and in human umbilical vein endothelial cells about 5-fold.","source_key":"import-33bef151-bdc7-5892-aff6-0345ab149739","source_title":"Nattokinase: what the purified enzyme cleaves, what survives being eaten, and the gap between the two (2026-09-23)","claim_ids":["5635aaba-e621-5bbf-b955-d485bbf14537"]},{"conflict_id":"e0314277-7470-54a9-97b8-87c73756706b","ordinal":1,"label":"Active nattokinase lowered adrenaline-stimulated tPA secretion from endothelium","revision_id":"efd063e6-e982-5f6e-a4b8-6f2ffe4185ce","start_line":444,"end_line":444,"quote":"In human umbilical vein endothelial cells, nattokinase reduced adrenaline-stimulated secretion of tissue-type plasminogen activator.","source_key":"import-33bef151-bdc7-5892-aff6-0345ab149739","source_title":"Nattokinase: what the purified enzyme cleaves, what survives being eaten, and the gap between the two (2026-09-23)","claim_ids":["a0650079-11b6-502d-b08e-8762866b8736"]}]}],"corrections":[],"research":null}