{"id":"90c57630-3489-50b5-94d9-0f3263cf3fe5","stable_key":"1fb6218a-60d1-55ea-87fe-07d15d0fc46f:geranylgeraniol-rescues-statin-myotoxicity","predicate":"increases","statement":"Geranylgeraniol fully reverted statin-mediated loss of myoblast viability, while water-soluble cholesterol did not, and statins caused loss of prenylated RAP1.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"positive","is_public":true,"mechanism_event_id":"9f8b0e67-f312-501f-85b6-ef6ef08dfdef","mechanism_event_label":"Geranylgeraniol fully reverted statin-mediated loss of myoblast viability, while water-soluble cholesterol did not, and statins caused loss of prenylated RAP1.","subject":{"id":"cafbbbdd-e9a7-520f-8667-8a0fbb7d8be0","slug":"geranylgeraniol","display_name":"Geranylgeraniol / GGOH","entity_type_key":"small_molecule"},"object":{"id":"1171c6b1-5e14-5a93-8e7c-ec115334c726","slug":"c2c12-myoblast-viability","display_name":"C2C12 myoblast viability","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"9f8b0e67-f312-501f-85b6-ef6ef08dfdef","stable_key":"1fb6218a-60d1-55ea-87fe-07d15d0fc46f:geranylgeraniol-rescues-statin-myotoxicity-event","event_type":"observed_relationship","label":"Geranylgeraniol fully reverted statin-mediated loss of myoblast viability, while water-soluble cholesterol did not, and statins caused loss of prenylated RAP1.","description":"Geranylgeraniol fully reverted statin-mediated loss of myoblast viability, while water-soluble cholesterol did not, and statins caused loss of prenylated RAP1.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"cafbbbdd-e9a7-520f-8667-8a0fbb7d8be0","slug":"geranylgeraniol","display_name":"Geranylgeraniol / GGOH","entity_type_key":"small_molecule"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"1171c6b1-5e14-5a93-8e7c-ec115334c726","slug":"c2c12-myoblast-viability","display_name":"C2C12 myoblast viability","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"a15c2e39-3b75-5c30-b45c-864ab6bc8e64","slug":"rap1-prenylation","display_name":"Prenylation of RAP1","entity_type_key":"cellular_process"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"64f4b2c7-afdf-5b9a-b6f9-015a7aa96eee","slug":"atorvastatin","display_name":"Atorvastatin","entity_type_key":"small_molecule"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":3,"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":"Murine C2C12 myoblasts","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Geranylgeraniol, farnesol, mevalonate or water-soluble cholesterol co-treatment with statin","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Cholesterol rescued only methyl-beta-cyclodextrin toxicity, and geranylgeranyltransferase inhibition with GGTI-286 could not be reversed by geranylgeraniol, so the rescue requires the transferase to be intact.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"organism","value_text":"Murine C2C12 myoblasts","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"Geranylgeraniol fully reverted statin-mediated loss of myoblast viability, while water-soluble cholesterol did not, and statins caused loss of prenylated RAP1.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"Geranylgeraniol Prevents Statin-Dependent Myotoxicity in C2C12 Muscle Cells through RAP1 GTPase Prenylation and Cytoskeletal Stabilization. (2018). https://pubmed.ncbi.nlm.nih.gov/29951166/ DOI: 10.1155/2018/6463807","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"route","value_text":"In vitro","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue","value_text":"Prenylation of RAP1 and muscle cell viability","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"36547ab7-76d6-53c2-9f95-ccd29f28dac9","evidence_kind":"source_excerpt","locator":"Lines 122-131","start_line":122,"end_line":131,"excerpt":"## geranylgeraniol-rescues-statin-myotoxicity\nGeranylgeraniol fully reverted statin-mediated loss of myoblast viability, while water-soluble cholesterol did not, and statins caused loss of prenylated RAP1.\nModel/species: Murine C2C12 myoblasts\nTissue/system: Prenylation of RAP1 and muscle cell viability\nExposure: Geranylgeraniol, farnesol, mevalonate or water-soluble cholesterol co-treatment with statin\nRoute: In vitro\nDuration: Not stated here\nLimits: Cholesterol rescued only methyl-beta-cyclodextrin toxicity, and geranylgeranyltransferase inhibition with GGTI-286 could not be reversed by geranylgeraniol, so the rescue requires the transferase to be intact.\nPrimary reference: Geranylgeraniol Prevents Statin-Dependent Myotoxicity in C2C12 Muscle Cells through RAP1 GTPase Prenylation and Cytoskeletal Stabilization. (2018). https://pubmed.ncbi.nlm.nih.gov/29951166/ DOI: 10.1155/2018/6463807\nAccess: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.","model_system":"","directness":"reported_statement","verification_status":"source_derived_draft","notes":"","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"a4431d8c-34d7-5db7-9edf-a35f68feba39","stable_key":"import-1fb6218a-60d1-55ea-87fe-07d15d0fc46f","title":"Atorvastatin: mechanism of action from target occupancy to isoprenoids, transport, muscle and metabolism (2026-09-22)","document_type":"imported_text","citation_label":"Original AI-assisted curation of twelve primary studies resolved by PubMed title search and cross-checked against live PubMed metadata. Findings obtained with mevastatin, simvastatin or the statin class are recorded against those subjects. Study-specific citations, doses, negative findings and limitations retained. 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