title: Mass spectrometric characterization of human serum albumin dimer: A new potential biomarker in chronic liver diseases.
abstract: Human serum albumin (HSA) undergoes several structural alterations affecting its properties in pro-oxidant and pro-inflammatory environments, as it occurs during liver cirrhosis. These modifications include the formation of albumin dimers. Although HSA dimers were reported to be an oxidative stress biomarker, to date nothing is known about their role in liver cirrhosis and related complications. Additionally, no high sensitive analytical method was available for HSA dimers assessment in clinical settings. Thus the HSA dimeric form in human plasma was characterized by mass spectrometry using liquid chromatography tandem mass spectrometry (LC-ESI-Q-TOF) and matrix assisted laser desorption time of flight (MALDI-TOF) techniques. N-terminal and C-terminal truncated HSA, as well as the native HSA, undergo dimerization by binding another HSA molecule. This study demonstrated the presence of both homo- and hetero-dimeric forms of HSA. The dimerization site was proved to be at Cys-34, forming a disulphide bridge between two albumin molecules, as determined by LC-MS analysis after tryptic digestion. Interestingly, when plasma samples from cirrhotic subjects were analysed, the dimer/monomer ratio resulted significantly increased when compared to that of healthy subjects. These isoforms could represent promising biomarkers for liver disease. Additionally, this analytical approach leads to the relative quantification of the residual native HSA, with fully preserved structural integrity.
authors.affiliation: Department of Pharmacy and Biotechnology, Alma Mater Studiorum University of Bologna, Italy; Center for Applied Biomedical Research (C.R.B.A.), S. Orsola-Malpighi University Hospital, Bologna, Italy.
authors.forename: Marina
authors.initials: M
authors.lastname: Naldi
authors.affiliation: Center for Applied Biomedical Research (C.R.B.A.), S. Orsola-Malpighi University Hospital, Bologna, Italy; Department of Medical and Surgical Sciences, Alma Mater Studiorum University of Bologna, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Baldassarre
authors.affiliation: Center for Applied Biomedical Research (C.R.B.A.), S. Orsola-Malpighi University Hospital, Bologna, Italy.
authors.forename: Marina
authors.initials: M
authors.lastname: Nati
authors.affiliation: Center for Applied Biomedical Research (C.R.B.A.), S. Orsola-Malpighi University Hospital, Bologna, Italy; Department of Medical and Surgical Sciences, Alma Mater Studiorum University of Bologna, Italy.
authors.forename: Maristella
authors.initials: M
authors.lastname: Laggetta
authors.affiliation: Center for Applied Biomedical Research (C.R.B.A.), S. Orsola-Malpighi University Hospital, Bologna, Italy; Department of Medical and Surgical Sciences, Alma Mater Studiorum University of Bologna, Italy.
authors.forename: Ferdinando Antonino
authors.initials: FA
authors.lastname: Giannone
authors.affiliation: Center for Applied Biomedical Research (C.R.B.A.), S. Orsola-Malpighi University Hospital, Bologna, Italy; Department of Medical and Surgical Sciences, Alma Mater Studiorum University of Bologna, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Domenicali
authors.affiliation: Center for Applied Biomedical Research (C.R.B.A.), S. Orsola-Malpighi University Hospital, Bologna, Italy; Department of Medical and Surgical Sciences, Alma Mater Studiorum University of Bologna, Italy.
authors.forename: Mauro
authors.initials: M
authors.lastname: Bernardi
authors.affiliation: Center for Applied Biomedical Research (C.R.B.A.), S. Orsola-Malpighi University Hospital, Bologna, Italy; Department of Medical and Surgical Sciences, Alma Mater Studiorum University of Bologna, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Caraceni
authors.affiliation: Department of Pharmacy and Biotechnology, Alma Mater Studiorum University of Bologna, Italy. Electronic address: carlo.bertucci@unibo.it.
authors.forename: Carlo
authors.initials: C
authors.lastname: Bertucci
mesh_terms: D015415:Biomarkers / Q000097:blood* / Q000737:chemistry*; D002908:Chronic Disease; D005260:Female; D006801:Humans; D008103:Liver Cirrhosis / Q000097:blood*; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress / Q000502:physiology; D020033:Protein Isoforms / Q000097:blood* / Q000737:chemistry*; D055503:Protein Multimerization; D012709:Serum Albumin / Q000096:biosynthesis / Q000737:chemistry*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods
chemical_list: D015415:Biomarkers; D020033:Protein Isoforms; D012709:Serum Albumin
keywords: Albumin dimers; Biomarkers; Human serum albumin isoforms; Mass spectrometry; Post-translational modifications