Inhaled Anesthetics Promote Albumin Dimerization through Reciprocal Exchange of Subdomains.

Inhaled anesthetics affect protein-protein interaction, but the mechanisms underlying these effects are still poorly understood. We examined the impact of sevoflurane and isoflurane on the dimerization of human serum albumin (HSA), a protein with anesthetic binding sites that are well characterized. Intrinsic fluorescence emission was analyzed for spectral shifting and self-quenching, and control first derivatives (spectral responses to changes in HSA concentration) were compared against those obtained from samples treated with sevoflurane or isoflurane. Sevoflurane increased dimer-dependent self-quenching and both decreased oligomer-dependent spectral shifting, suggesting that inhaled anesthetics promoted HSA dimerization. Size exclusion chromatography and polarization data were consistent with these observations. The data support the proposed model of a reciprocal exchange of subdomains to form an HSA dimer. The open-ended exchange of subdomains, which we propose occuring in HSA oligomers, was inhibited by sevoflurane and isoflurane.

Interfacial effects on the conformation of amyloid-beta peptide.

We examined the effects of air-water and water-sevoflurane interfaces on conformational properties of amyloid-beta peptide (ABP). Fractions were extracted from sub-interfacial (air-water) and supra-interfacial (water-sevoflurane) layers and compared with aqueous bulk layers using fluorescence properties of ABP provided by a single tyrosine. The observations suggest that interfacial ABP may be more disordered than bulk ABP.

Trifluoroethanol increases albumin's susceptibility to chemical modification.

Acrolein-dependent chemical modification is implicated in the etiology of postoperative cognitive dysfunction (POCD). We examined this process further using human serum albumin (HSA), which is a target of acrolein modification and contains anesthetic binding sites. We tested whether trifluoroethanol (TFE), which mimics inhaled anesthetics, affects the susceptibility of HSA to modification by acrolein. We observed that acrolein promoted the formation of fluorescent adducts. TFE (10%) increased the amount of acrolein-HSA adducts. TFE (40%) caused a 5-fold increase in adduct formation. Acrolein also increased tryptophan anisotropy of HSA, which was further increased by TFE (10%). Acrolein-induced protein cross-linking was also increased in the presence of TFE (40%). These observations suggest that TFE promotes acrolein-induced modification of HSA, supporting a putative mechanism for POCD.