title: Inhaled Anesthetics Promote Albumin Dimerization through Reciprocal Exchange of Subdomains.
abstract: 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.
authors.affiliation: Department of Anesthesiology, University of Missouri-Kansas City School of Medicine, 4401 Wornall Road, Kansas City, MO 64111, USA.
authors.forename: Benjamin J
authors.initials: BJ
authors.lastname: Pieters
authors.forename: Eugene E
authors.initials: EE
authors.lastname: Fibuch
authors.forename: Joshua D
authors.initials: JD
authors.lastname: Eklund
authors.forename: Norbert W
authors.initials: NW
authors.lastname: Seidler