Sublethal heat shock and cyclosporine exposure produce tolerance against subsequent cyclosporine toxicity

Christina M. Yuan*, Erin M. Bohen, Franco Musio, Michael A. Carome

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

24 Scopus citations


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°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 l 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 ug/ml) for 24 h produced upregulation of HSP-70 mRNA and protein. Pretreatment with 50 μg/ml CyA for 24 h followed by exposure to a toxic concentration of CyA (200 μg/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.

Original languageEnglish
Pages (from-to)F571-F578
JournalAmerican Journal of Physiology
Issue number3 PART 2
StatePublished - 1996


  • Cyclophilin
  • Cytotoxicity
  • Heat shock protein-70
  • Kidney
  • Tubule


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