{"id":"f8b59547-19dc-5d3b-b0ce-866edb23680d","stable_key":"e0ea2d6a-7429-5e9f-b774-41e5e3288da3:e-sig-alpha-pkc-cofactor","predicate":"inhibits","statement":"RRR-alpha-tocopherol at 0.1–10 µM inhibited cofactor-dependent recombinant human PKC alpha activity in phosphatidylserine-containing assays.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"negative","is_public":true,"mechanism_event_id":"5b8e0f82-b68d-54ee-b366-ad69115945a1","mechanism_event_label":"Natural alpha-tocopherol reduced PKC alpha activity in a purified system containing its lipid and calcium cofactors.","subject":{"id":"ae6048a7-d112-5d3a-8e7c-ad5a152642f9","slug":"rrr-alpha-tocopherol","display_name":"RRR-alpha-tocopherol","entity_type_key":"small_molecule"},"object":{"id":"d4c19e4b-d83b-5cda-8c7d-041d7fe6ada0","slug":"prkca","display_name":"Protein kinase C alpha (PRKCA)","entity_type_key":"protein"},"evidence_count":1,"mechanism_event":{"id":"5b8e0f82-b68d-54ee-b366-ad69115945a1","stable_key":"e0ea2d6a-7429-5e9f-b774-41e5e3288da3:e-sig-alpha-pkc-cofactor-event","event_type":"biochemical_relationship","label":"Natural alpha-tocopherol reduced PKC alpha activity in a purified system containing its lipid and calcium cofactors.","description":"RRR-alpha-tocopherol at 0.1–10 µM inhibited cofactor-dependent recombinant human PKC alpha activity in phosphatidylserine-containing assays.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"e359bc15-e675-5d83-b0fe-1d70814e130b","slug":"calcium-ion","display_name":"Calcium ion","entity_type_key":"ion"},"role":"cofactor","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"0e2dd859-6135-556e-938f-d177f1e8c1ad","slug":"phosphatidylserine","display_name":"Phosphatidylserine","entity_type_key":"lipid"},"role":"lipid cofactor","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"ae6048a7-d112-5d3a-8e7c-ad5a152642f9","slug":"rrr-alpha-tocopherol","display_name":"RRR-alpha-tocopherol","entity_type_key":"small_molecule"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"d4c19e4b-d83b-5cda-8c7d-041d7fe6ada0","slug":"prkca","display_name":"Protein kinase C alpha (PRKCA)","entity_type_key":"protein"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""}]},"contexts":[{"dimension":"cross_nutrient","value_text":"true","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Recombinant HIS-tagged human PKC alpha biochemical assay","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"15 ng PKC alpha; 2 mM CaCl2; phosphatidylserine 15–60 µg/mL; 5 min pretreatment, 30 min kinase assay.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Effect depends on reconstituted lipid composition and activation mode; it is not a clinical dosing claim.","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":"Homo sapiens","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"Natural alpha-tocopherol reduced PKC alpha activity in a purified system containing its lipid and calcium cofactors.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[mccary2012] Vitamin E isoforms directly bind PKCα and differentially regulate activation of PKCα. (2012). https://pubmed.ncbi.nlm.nih.gov/21933153/ DOI: 10.1042/bj20111318","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Cell-free enzyme","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"ace463b9-f044-5179-bc19-9cfc44e811fa","evidence_kind":"source_excerpt","locator":"Lines 933-944","start_line":933,"end_line":944,"excerpt":"### e-sig-alpha-pkc-cofactor\nRRR-alpha-tocopherol at 0.1–10 µM inhibited cofactor-dependent recombinant human PKC alpha activity in phosphatidylserine-containing assays.\nCondition category: normal\nnutrient_topic: Vitamin E research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: Natural alpha-tocopherol reduced PKC alpha activity in a purified system containing its lipid and calcium cofactors.\norganism: Homo sapiens\ntissue_or_cell_type: Cell-free enzyme\nexperimental_model: Recombinant HIS-tagged human PKC alpha biochemical assay\nlimitations: Effect depends on reconstituted lipid composition and activation mode; it is not a clinical dosing claim.\nexposure: 15 ng PKC alpha; 2 mM CaCl2; phosphatidylserine 15–60 µg/mL; 5 min pretreatment, 30 min kinase assay.\ncross_nutrient: true\n[mccary2012] Vitamin E isoforms directly bind PKCα and differentially regulate activation of PKCα. 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