Calmodulin inhibitors potentiate hyperthermic cell killing.
The role of calmodulin (CaM) in cellular heat injury of neuroblastoma N2A and hepatoma H35 cells has been investigated, using specific calmodulin-inhibiting drugs (Trifluoperazine, Compound 48/80 and Calmidazolium). These CaM-specific drugs potentiate hyperthermia-induced cell killing, suggesting CaM to be involved in processes aimed on the repair of heat injury. The CaM inhibitors also prevent hyperthermia-induced cytoskeletal alterations in the cell types studied. The action of CaM inhibitors was dose dependent, and seems to be confined to the first period of the hyperthermic treatment. Neither production of heat shock proteins in heat-shocked cultures, nor the rate of protein synthesis in control cultures were affected by the CaM inhibitors. It was concluded that an inverse correlation exists between hyperthermic cell killing and cytoskeletal alterations. Activation of CaM is suggested to be a fundamental aspect of the cellular heat shock response.
D000818:Animals; D002147:Calmodulin / Q000037:antagonists & inhibitors*; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D002478:Cells, Cultured; D003131:Combined Modality Therapy; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D004357:Drug Synergism; D005455:Fluorescent Antibody Technique; D006979:Hyperthermia, Induced; D007093:Imidazoles / Q000627:therapeutic use; D008114:Liver Neoplasms, Experimental / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000528:radiation effects; D009447:Neuroblastoma / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D051381:Rats; D013997:Time Factors; D014268:Trifluoperazine / Q000627:therapeutic use; D003189:p-Methoxy-N-methylphenethylamine / Q000627:therapeutic use
D002147:Calmodulin; D007093:Imidazoles; D009363:Neoplasm Proteins; D014268:Trifluoperazine; D003189:p-Methoxy-N-methylphenethylamine; C031938:calmidazolium