6533b851fe1ef96bd12a8ee8
RESEARCH PRODUCT
Glycation alters ligand binding, enzymatic, and pharmacological properties of human albumin.
Philippe RondeauPhilippe RondeauJennifer Baraka-vidotJennifer Baraka-vidotCynthia PlanesseCynthia PlanesseOlivier MeilhacOlivier MeilhacEmmanuel BourdonEmmanuel BourdonValeria MilitelloJean M. H. Van Den Elsensubject
Glycation End Products AdvancedGlycosylationGlycosylationSerum albuminContext (language use)Plasma protein bindingProtein aggregationBiochemistryChromatography AffinityMass SpectrometryProtein Structure Secondarychemistry.chemical_compoundGlycationAlbuminsBlood plasmaHumansGlycated Serum AlbuminSerum AlbuminbiologyAlbuminAlbuminSettore FIS/07 - Fisica Applicata(Beni Culturali Ambientali Biol.e Medicin)Spectrometry FluorescencechemistryBiochemistryKetoprofenbiology.proteinHumanProtein Bindingdescription
Albumin, the major circulating protein in blood plasma, can be subjected to an increased level of glycation in a diabetic context. Albumin exerts crucial pharmacological activities through its drug binding capacity, i.e., ketoprofen, and via its esterase-like activity, allowing the conversion of prodrugs into active drugs. In this study, the impact of the glucose-mediated glycation on the pharmacological and biochemical properties of human albumin was investigated. Aggregation product levels and the redox state were quantified to assess the impact of glycation-mediated changes on the structural properties of albumin. Glucose-mediated changes in ketoprofen binding properties and esterase-like activity were evaluated using fluorescence spectroscopy and p-nitrophenyl acetate hydrolysis assays, respectively. With the exception of oxidative parameters, significant dose-dependent alterations in biochemical and functional properties of in vitro glycated albumin were observed. We also found that the dose-dependent increase in levels of glycation and protein aggregation and average molecular mass changes correlated with a gradual decrease in the affinity of albumin for ketoprofen and its esterase-like property. In parallel, significant alterations in both pharmacological properties were also evidenced in albumin purified from diabetic patients. Partial least-squares regression analyses established a significant correlation between glycation-mediated changes in biochemical and pharmacological properties of albumin, highlighting the important role for glycation in the variability of the drug response in a diabetic situation.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2015-04-28 | Biochemistry |