title: Sublethal heat shock and cyclosporine exposure produce tolerance against subsequent cyclosporine toxicity.
abstract: Sublethal heat shock has been shown to produce tolerance in cells and tissues subsequently exposed to heat or ischemia/ATP depletion. We tested whether heating LLC-PK1 cells for 2 h at 42 degrees C induced heat shock protein-70 (HSP-70) gene expression and conferred tolerance against subsequent cyclosporine A (CyA) toxicity. HSP-70 mRNA was increased immediately after heat shock, returning to baseline by 4 h. HSP-70 protein increased by 1 h after heat shock and declined thereafter, approaching baseline after 72 h. Cells heat shocked at 4 and 24 h prior to CyA exposure were significantly more viable than controls, at CyA concentrations near the median lethal dose (LD50). Cytoprotection declined with time after heat shock, concurrent with declining HSP-70 protein levels. Sublethal CyA exposure (50 micrograms/ml) for 24 h produced upregulation of HSP-70 mRNA and protein. Pretreatment with 50 micrograms/ml CyA for 24 h followed by exposure to a toxic concentration of CyA (200 micrograms/ml) produced significant cytoprotection compared with untreated controls. In conclusion, HSP-70 protein induction by sublethal heat shock or CyA exposure was associated with tolerance against subsequent lethal CyA exposure.
authors.affiliation: Department of Medicine, Walter Reed Army Medical Center, Washington, District of Columbia 20307-5001, USA.
authors.forename: C M
authors.initials: CM
authors.lastname: Yuan
authors.forename: E M
authors.initials: EM
authors.lastname: Bohen
authors.forename: F
authors.initials: F
authors.lastname: Musio
authors.forename: M A
authors.initials: MA
authors.lastname: Carome
mesh_terms: D000818:Animals; D016572:Cyclosporine / Q000506:poisoning*; D004361:Drug Tolerance; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D018869:Heat-Shock Response / Q000502:physiology*; D007684:Kidney Tubules / Q000166:cytology / Q000187:drug effects*; D018374:LLC-PK1 Cells; D012333:RNA, Messenger / Q000378:metabolism; D013552:Swine; D013997:Time Factors
chemical_list: D018840:HSP70 Heat-Shock Proteins; D012333:RNA, Messenger; D016572:Cyclosporine