Background and Goal of Study:Anesthetic action and preconditioning are conserved across all living organisms. S. cerevisiae is a eukaryotic organism whose growth is inhibited by halogenated anesthetic compounds (1). Moreover, when exposed to a moderate stress, its cellular stress response is activated, making it more resistant to subsequent more severe stresses of the same or a different kind (2). We hypothesize that anesthetics can also invoke the cellular stress response in yeast protecting it from an otherwise lethal heat stress.

Materials and Methods: Anesthetic potency was determined by measuring growth inhibition through optical density of S. cerevisiae w303 yeast culture in presence of carbon tetrabromide (CBr4), 2,2,2-tribromoethanol (TBE), 2,2.2-trichloroethanol (TCE), 1,1,1,3,3,3-hexafluoroisopropanol (HFP), 2,2,2-trifluoroethanol (TFE) and ethanol (EtOH). Potency for protection was determined by comparing colony forming units after exposure to a usually lethal heat stress with and without pretreatment with a concentration range of the anesthetic compounds.

Results and Discussion: The studied halogenated alcohol and alkane anesthetics dose-dependently inhibit S. cerevisiae growth. EC50 for anesthetic activity of CBr4, TBE, TCE, HFP, TFE and EtOH are 300µM (95% CI: 110-824µM), 400µM (95% CI: 300-540µM), 800µM (95% CI 625-896µM), 2.74mM (95% CI: 2.00-3.65mM), 5.57mM (95% CI: 4.08-7.71mM) and 132mM (95% CI: 55.7-879mM), respectively (n=3 for each concentration). The rank order of the anesthetic compounds for protection correlates with their anesthetic potency. Maximum effective doses for CBr4, TBE, TCE, HFP, TFE and EtOH are 40µM, 5.3mM (SEM±2.6), 30mM, 40mM, 270mM (SEM±90) and 770mM respectively (n=1-3 for each concentration).

Conclusion: Halogenated alcohol and alkane anesthetics protect yeast from an otherwise lethal heat stress. Yeast is a useful model organism for studying the underlying mechanisms for anesthetic preconditioning and to determine a structure activity relationship of preconditioning agents.

References: (1) Sonner JM, Anesthesia and analgesia 2008, 107(3):849.(2) Plesset J, Palm C, McLaughlin C, Biochemical and biophysical research communications 1982, 108(3):1340-1345.

03 / Pretreatment with halogenated alcohol and alkane anesthetics protects S. cerevisiae yeast from heat stress.