Isoflurane preconditioning involves upregulation of molecular chaperone genes

Isoflurane preconditioning is a phenomenon in which cells previously exposed to isoflurane exhibit protection against subsequent noxious stimuli. We hypothesize that isoflurane may cause subtle protein misfolding that persists at a sublethal level, stimulating cytoprotective mechanisms. Human neuroblastoma cells (SH-SY5Y) were exposed to isoflurane followed by quantitative analysis of the expression of several families of heat shock genes (84 total transcripts). Our data is consistent with a model of an early and delayed phase of preconditioning. Different patterns of expression of the 84 genes were seen at 1 and 24h post-isoflurane exposure. Expression of 45 of the 84 genes were elevated at 1h (or early phase) and remained upregulated at 24h (or delayed phase). Subsets of the remaining genes were either unchanged (13 genes), early-specific upregulated (17 genes) or delayed-specific upregulated (9 genes). We also demonstrated that isoflurane caused a slight yet detectable misfold of a model protein. These data indicate that brief anesthetic exposure promotes specific patterns of gene expression, leading to preconditioning which would enhance the cell's ability to tolerate a future injury that involves protein misfolding.