Structural and functional profile of human serum albumin: clinical implications and prognostic relevance

Carlo Bertucci, Pharmacy and Biotechnology, University of Bologna, Bologna, Italy (carlo.bertucci@unibo.it)
Marina Naldi, Department of Pharmacy and Biotechnology, University of Bologna, Italy
Center for Applied Biomedical Research (C.R.B.A.), S. Orsola-Malpighi Hospital, Bologna, Italy
Maurizio Baldassarre, Center for Applied Biomedical Research (C.R.B.A.), S. Orsola-Malpighi Hospital, Bologna, Italy
Department of Medical and Surgical Sciences, University of Bologna, Italy
Martina Gagliardi, Center for Applied Biomedical Research (C.R.B.A.), S. Orsola-Malpighi Hospital, Bologna, Italy
Department of Medical and Surgical Sciences, University of Bologna, Italy
Jonathan Montomoli, Department of Hepatology and Gastroenterology, Aarhus University Hospital, Denmark
Thomas Damgaard Sandahl, Department of Hepatology and Gastroenterology, Aarhus University Hospital, Denmark
Emilie Glavind, Department of Hepatology and Gastroenterology, Aarhus University Hospital, Denmark
Hendrik Vilstrup, Department of Hepatology and Gastroenterology, Aarhus University Hospital, Denmark
Paolo Caraceni, Department of Medical and Surgical Sciences, University of Bologna, Italy
Department of Hepatology and Gastroenterology, Aarhus University Hospital, Denmark

Notwithstanding human serum albumin (HSA) is one of the most studied plasma proteins, it continues to attract the research interest. Along with its oncotic properties and thanks to its peculiar structure, HSA is endowed with many “non oncotic properties” which include the fine regulation of the plasma redox state, the modulation of the inflammatory and/or immunological responses and the capacity of binding several endogenous or exogenous molecules [1]. Moreover, HSA plasma concentration has shown to be a valuable biomarker in many diseases and pharmaceutical grade formulation of this protein is widely used for the treatment of shock, hypoproteinemia and burns. Unfortunately, in pathological but also in physiological conditions HSA structure may undergoes several post-translational modifications (PTMs) such as reversible and irreversible oxidation, truncation and glycation; recent studies have shown that extensive PTMs associated with liver cirrhosis affect HSA structure and functionality [2].  

In the light of the key physiological role of HSA, the assessment of disease-related PTMs is of pivotal interest. To this aim, we have developed and validated an analytical methodology based on reverse phase liquid chromatography (RPLC) coupled to electrospray ionization mass spectrometry (ESI-MS) for the identification of HSA structural alterations as well as HSA dimerization occurring in a large cohort of cirrhotic patients (n=144). Interestingly this study showed a fine correlation between altered HSA isoforms and disease severity, clinical complications and patients’ survival. Moreover, the analysis of altered HSA structure in a population of patients affected by alcoholic hepatitis (AH) (n=20) showed that the severe oxidative stress experienced by AH patients caused profound changes in circulating HSA micro-heterogeneity

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Abstract Reference & Short Personal Biography of Presenting Author

[1] M. Naldi, M. Baldassarre, M. Domenicali, M. Bartolini, P. Caraceni. Structural and functional integrity of human serum albumin: Analytical approaches and clinical relevance in patients with liver cirrhosis. JPBA, 144 (2017) 138-153.

[2] K. Oettl, R. Birner-Gruenberger, W. Spindelboeck, H. Peter Stueger, L. Dorn, V. Stadlbauer, C. Putz-Bankuti,  P. Krisper, I. Graziadei, W. Vogel, C. Lackner, R. E. Stauber. Oxidative albumin damage in chronic liver failure: Relation to albumin binding capacity, liver dysfunction and survival. Journal of Hepatology  59 (2013) 978–983.

Full Professor of Medicinal Chemistry University of Bologna, Italy. Visiting Professor at Oregon State University, Corvallis, Oregon, USA: 1980, 1982, 1984, 1985; at The University of São Paulo, School of Pharmacy at Ribeirão Preto, Brazil, 1989, 2006, 2008, 2010, 2011, 2012; at McGill University, Montreal, Canada, 1995; at the University of Bordeaux, Francia, 1997; at the Georgetown University, Washington DC, USA, 2000.

The scientific activity of Prof. Carlo Bertucci mainly deals with the structural characterization of drugs and proteins, the study of the biorecognition mechanisms in the drug/target protein and protein/protein binding. In particular: enantioselective HPLC and circular dichroism based detection system; absolute configuration assignment to chiral drugs; structural characterization of peptides and proteins by spectroscopic and spectrometric techniques; drug binding to target proteins by biocromatography, SPR biosensor and chiroptical spectroscopy; monitoring and modulation of conformational transition of peptides and proteins having physiological or pathological relevance.

He is member of the Editorial Advisory Board of the Journal Chirality and of the Journal of Pharmaceutical and Biomedical Analysis.

He is the author, or co-author, of some 200 papers or reviews in international journals, 1 patent, 8 chapters in books, 1 entry in an encyclopaedia.