Inhaled Anesthetics Promote Albumin Dimerization through Reciprocal Exchange of Subdomains

Abstract EN

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.