{"id":"5b84034e-395d-5d30-b8b1-82a0f46537d4","stable_key":"7edf94bb-95c8-5234-9161-9eb338bb9b36:boron-perk-eif2alpha-dependence","predicate":"required_for_response_of","statement":"Boric acid induced eIF2α Ser51 phosphorylation in wild-type mouse fibroblasts at one hour, but not in Perk-null cells tested for up to six hours.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"5f75801c-9116-59db-b1e4-254e6d5c9df0","mechanism_event_label":"Removing PERK blocked this step of the boric-acid response.","subject":{"id":"2edd7451-da61-56c4-9312-6facc42f6919","slug":"mouse-eif2ak3","display_name":"Mouse PERK / Eif2ak3","entity_type_key":"protein"},"object":{"id":"fc8e1dad-14a4-5aa0-856a-d63340fa3187","slug":"mouse-eif2s1","display_name":"Mouse eIF2α / Eif2s1","entity_type_key":"protein"},"evidence_count":1,"mechanism_event":{"id":"5f75801c-9116-59db-b1e4-254e6d5c9df0","stable_key":"7edf94bb-95c8-5234-9161-9eb338bb9b36:boron-perk-eif2alpha-dependence-event","event_type":"biochemical_relationship","label":"Removing PERK blocked this step of the boric-acid response.","description":"Boric acid induced eIF2α Ser51 phosphorylation in wild-type mouse fibroblasts at one hour, but not in Perk-null cells tested for up to six hours.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"56db2f3c-f247-573f-bb7c-47cac02ea60f","slug":"boric-acid","display_name":"Boric acid / orthoboric acid / B(OH)3","entity_type_key":"small_molecule"},"role":"exposure","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"2edd7451-da61-56c4-9312-6facc42f6919","slug":"mouse-eif2ak3","display_name":"Mouse PERK / Eif2ak3","entity_type_key":"protein"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"fc8e1dad-14a4-5aa0-856a-d63340fa3187","slug":"mouse-eif2s1","display_name":"Mouse eIF2α / Eif2s1","entity_type_key":"protein"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""}]},"contexts":[{"dimension":"availability_state","value_text":"machinery_impairment","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null},{"dimension":"evidence_span","value_text":"{\"source_cache\": \"artifacts/boron-research/30196486.abstract.txt\", \"locator\": \"Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"e220df5fb0f9b8653035f7a144259ce66778467a7a72acbf7cd7d113f8b6030a\", \"start_char\": 0, \"end_char\": 2006, \"text_sha256\": \"e220df5fb0f9b8653035f7a144259ce66778467a7a72acbf7cd7d113f8b6030a\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"PERK knockout comparison, immunofluorescence and quantitative PCR","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"10 µM boric acid; 1–6 hour comparisons","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Knockout dependence in mouse fibroblasts is separate from human tumor-cell transcription. Increased GCLC mRNA is not a measured increase in glutathione synthesis or clinical antioxidant benefit.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Boron research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"boron","display_name":"Boron","entity_type_key":"nutrient_element"}},{"dimension":"organism","value_text":"Mouse embryonic fibroblasts and human DU-145 cells","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"Removing PERK blocked this step of the boric-acid response.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[boron-p30196486] Boric Acid Activation of eIF2α and Nrf2 Is PERK Dependent: a Mechanism that Explains How Boron Prevents DNA Damage and Enhances Antioxidant Status. (2019). https://pubmed.ncbi.nlm.nih.gov/30196486/ DOI: 10.1007/s12011-018-1498-4","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Cell culture","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":"e5369c07-e07d-5f8c-9e4f-d070a64bfa16","evidence_kind":"source_excerpt","locator":"Lines 495-506","start_line":495,"end_line":506,"excerpt":"### boron-perk-eif2alpha-dependence\nBoric acid induced eIF2α Ser51 phosphorylation in wild-type mouse fibroblasts at one hour, but not in Perk-null cells tested for up to six hours.\nCondition category: machinery_impairment\nnutrient_topic: Boron research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: Removing PERK blocked this step of the boric-acid response.\norganism: Mouse embryonic fibroblasts and human DU-145 cells\ntissue_or_cell_type: Cell culture\nexperimental_model: PERK knockout comparison, immunofluorescence and quantitative PCR\nlimitations: Knockout dependence in mouse fibroblasts is separate from human tumor-cell transcription. Increased GCLC mRNA is not a measured increase in glutathione synthesis or clinical antioxidant benefit.\nexposure: 10 µM boric acid; 1–6 hour comparisons\nevidence_span: {\"source_cache\": \"artifacts/boron-research/30196486.abstract.txt\", \"locator\": \"Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"e220df5fb0f9b8653035f7a144259ce66778467a7a72acbf7cd7d113f8b6030a\", \"start_char\": 0, \"end_char\": 2006, \"text_sha256\": \"e220df5fb0f9b8653035f7a144259ce66778467a7a72acbf7cd7d113f8b6030a\"}\n[boron-p30196486] Boric Acid Activation of eIF2α and Nrf2 Is PERK Dependent: a Mechanism that Explains How Boron Prevents DNA Damage and Enhances Antioxidant Status. (2019). https://pubmed.ncbi.nlm.nih.gov/30196486/ DOI: 10.1007/s12011-018-1498-4","model_system":"PERK knockout comparison, immunofluorescence and quantitative PCR","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [boron-p30196486] Boric Acid Activation of eIF2α and Nrf2 Is PERK Dependent: a Mechanism that Explains How Boron Prevents DNA Damage and Enhances Antioxidant Status. 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