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Contact data |
Associate Professor |
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Biography |
Mauro Fasano graduated in Chemistry with honors in 1989 and earned his Ph.D. in Chemical Sciences in 1992, both from the University of Torino, Italy. From 1992 to 2000 was appointed to a position of Assistant Professor of Chemistry at the School of Sciences of the University of Torino. From 2000 to present he is Associate Professor of Biochemistry at
the School of Sciences of the University of Insubria. |
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Qualifications and awards |
Vice-president of the Italian
NMR discussion group. President-elect of the life science division of the Italian Chemical Society. Member of the scientific board of the Proteome Chemistry discussion group of the Italian Chemical Society. |
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Research interests |
1. Applications of 1H-NMR
relaxometry in the investigation of heme-human serum albumin 2 . Human serum albumin (HSA), the most prominent protein in plasma, is best known for its exceptional ligand binding capacity. For many compounds, HSA provides a depot so they will be available in quantities well beyond their solubility in plasma. Moreover, HSA abundance (its concentration being 45 mg/mL, in the serum of human adults) makes it an important determinant of the pharmacokinetic behavior of many drugs. Among hydrophobic molecules, heme binding to HSA is of peculiar relevance for the heme iron reuptake following hemolytic events. Heme binding to HSA endows the protein with peculiar spectroscopic properties. Electronic absorption and relaxometric data indicate the occurrence of a high-spin Fe(III) center with no water in the inner coordination sphere, and the occurrence of a strong contribution from a cluster of water molecules buried nearby. This second-sphere contribution may be employed as a structure-dependent spectroscopic observable to follow a number of events involving the conformation of the protein. Among them, allosteric equilibria are investigated upon heterotropic interaction of drugs with primary transport sites of the protein. More recently, we investigated the effect of fatty acid binding to the N and B conformational states of Mn(III)heme-HSA (i.e., at pH 7.0 and 10.0, respectively) by optical absorbance and NMR spectroscopy. Myristate binding to a secondary site (FAx), allosterically coupled to the heme site, not only increases optical absorbance of Mn(III)heme-bound HSA by a factor of 3, but also increases the Mn(III)heme affinity for the fatty acid binding site FA1 by 10-500-fold. Cooperative binding appears to occur at FAx and accessory myristate binding sites. 3 . Differential protein expression in Parkinson’s Disease. 4 . Parkinson’s disease (PD) is the second most common neurodegenerative disorder after Alzheimer’s disease (AD), with a prevalence of 2-3% among people over the age of 65 years. The characteristic motor symptoms are associated with the depletion of dopaminergic melanin-containing neurons in the substantia nigra pars compacta (SNpc) and a consequent loss of dopamine in the striatum. Another important pathological feature is the presence, especially in SNpc neurons, of eosinophilic cytoplasmic inclusion bodies (Lewy bodies). Lewy bodies show a strong staining with anti- α -synucleins antibodies, a presynaptic protein involved in a familial form of the disease. In vitro studies showed that both mutated and wild type a -synucleins do form fibrils similar to those of Lewy bodies; moreover, α -synucleins molecules carrying either one of the three point mutations observed in the familial PD will aggregate faster than the wild type protein. 5. We performed a two-dimensional electrophoretic (2DE) separation of proteins extracted from ex vivo substantia nigra specimens from controls and PD patients. Forty-one proteins have been identified by peptide mass fingerprinting and their expression levels have been compared. Among them, nine proteins show differential expression in PD patients. 6. We have considered the effect of dopamine and of pro- and anti-oxidant factors on viability of a dopaminergic cell line (SH-SY5Y human neuroblastoma). Extracellular contribution to dopamine cell toxicity is ruled out by adding catalase that removes hydrogen peroxide formed by spontaneous dopamine oxidation. Cell death is reduced by 75% in the presence of catalase, and appears to be dose-dependent. Cu(II) ions appear to be a moderate determinant of reactive oxigen species, whereas the simultaneous presence of Cu(II) and glutathione leads to the occurrence of Cu(I)-catalysed Haber-Weiss cycle with a consequent decrease of cell viability. Expression of increased levels of wild-type alphα -synucleins through transfection of the cell line determines a cytoprotective effect. Transfected cells are more resistant to oxidative insults, whereas cells transfected with a control vector are not. |
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Teaching experience and appointments |
Mauro Fasano is teaching
Biochemistry and Biochemical Methods in the undergraduate courses
of Biology, Health Biology, and Biotechnology. In the graduate course
of Biology applied to Biomedical Research he is teaching biochemistry
modules in the courses of Experimental Biology, Basic Neuroscience
and Physiopathology of the immune system, and Proteomics in the graduate
course of Biology. Vice-director of the Department of Structural and Functional Biology. Scientific secretary of the Centre of Neuroscience. Director of the Master in Bioinformatics. Member of the Board of the doctorate school of cellular and molecular biology. Coordinator of the School Commission for Tutorial Activities. |
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Representative publications |
1. P. Ascenzi, M. Colasanti,
M. Fasano, A. Bertollini, “Stabilization of the T-state of human
hemoglobin by proflavine, an antiseptic drug”, Biochem. Mol.
Biol. Int., 47, 991-995 (1999). 2. S. Aime, B. Bergamasco, M. Casu, G. Digilio, M. Fasano, S. Giraudo, L. Lopiano, “Isolation and 13C-NMR characterization of an insoluble proteinaceous fraction from substantia nigra of patients with Parkinson’s Disease”, Mov. Disord. 15, 977-81 (2000). 3. L. Lopiano, M. Chiesa, G. Digilio, S. Giraudo, B. Bergamasco, E. Torre, M. Fasano, “Q-band EPR investigations of neuromelanin in control and Parkinson’s disease patients”, Biochim. Biophys. Acta, 1500, 306-312 (2000). 4. L. Lopiano, M. Fasano, S. Giraudo, G. Digilio, B. Bergamasco, E. Torre, S. H. Koenig, S. Aime, “Nuclear Magnetic Relaxation Dispersion profiles of Substantia Nigra pars compacta in Parkinson’s disease patients are consistent with protein aggregation”, Neurochem. Int. 37, 331-336 (2000). 5. M. Sette, M. Bozzi, A. Battistoni, M. Fasano, M. Paci, G. Rotilio, “Investigation of the active site of Escherichia coli Cu,Zn superoxide dismutase reveals the absence of the copper-coordinated water molecule. Is the water molecule really necessary for the enzymatic mechanism?”, FEBS Lett. 483, 21-26 (2000). 6. M. Mattu, A. Vannini, M. Coletta, M. Fasano, P. Ascenzi. “Effect of Bezafibrate and Clofibrate on the Heme-Iron Geometry of Ferrous Nitrosylated Human Serum Heme-Albumin: An EPR Study.”, J. Inorg. Biochem. 84, 293-296 (2001). 7. M. Fasano, S. Baroni, A. Vannini, P. Ascenzi, S. Aime, “Relaxometric investigations of human hemalbumin”, J. Biol. Inorg. Chem. 6, 650-658 (2001). 8. S. Baroni, M. Mattu, A. Vannini, R. Cipollone, S. Aime, P. Ascenzi, M. Fasano, “Effect of ibuprofen and warfarin on the allosteric properties of haem-human serum albumin. A spectroscopic study.” Eur. J. Biochem. 268, 6214-6220 (2001). 9. P. Ascenzi, M. Fasano, M. Marino, G. Venturini, R. Federico, “Agmatine oxidation by copper amine oxidase: biosynthesis and biochemical characterization of N-amidino-2-hydroxypyrrolidine”, Eur. J. Biochem. 269, 884-892 (2002). 10. F. Bolzoni, S. Giraudo, B. Bergamasco, L. Lopiano, M. Fasano, P.R. Crippa, “Magnetic investigations of human mesencephalic neuromelanin” Biochim. Biophys. Acta 1586, 210-218 (2002). 11. M. Fasano, M. Mattu, M. Coletta, P. Ascenzi, “The heme-iron geometry of ferrous nitrosylated heme-serum lipoproteins, hemopexin, and albumin: a comparative EPR study”, J. Inorg. Biochem. 91, 487-490 (2002). 12. P. Ascenzi, M. Fasano, L. Gradoni, “Do hemoglobin and hemocyanin impair Schistosoma killing by NO?”, IUBMB Life 53, 287-288 (2002). 13. D. Delli Castelli, E. Lovera, P. Ascenzi, M. Fasano, “Unfolding of the loggerhead sea turtle (Caretta caretta) myoglobin: A 1H-NMR and electronic absorbance study”. Protein Sci. 11, 2273-2278 (2002). 14. E. Monzani, M. Curto, M. Galliano, L. Minchiotti, S. Aime, S. Baroni, M. Fasano, A. Amoresano, A. M. Salzano, P. Pucci, L. Casella, “Binding and Relaxometric Properties of Heme Complexes with Cyanogen Bromide Fragments of Human Serum Albumin”, Biophys. J. 83, 2248-2258 (2002). 15. M. Mattu, M. Fasano, A. Spallarossa, M. Bolognesi, P. Ascenzi, “Hemopexin – The primary specific carrier of plasma heme” , Biochem. Mol. Biol. Educ. 30, 332-335 (2002). 16. M. Fasano, S. Giraudo, S. Coha, B. Bergamasco, L. Lopiano, “Residual substantia nigra neuromelanin in Parkinson’s disease is cross-linked to α -synucleins”. Neurochem. Int. 42, 603-606 (2003). 17. M. Fasano, S. Baroni, S. Aime, M. Mattu, P. Ascenzi, “Determination of ferric heme-human serum albumin by 1H-NMR relaxometry”. J. Inorg. Biochem. 95, 64-67 (2003). 18. M. Fasano, M. Orsale, S. Melino, E. Nicolai, F. Forlani, N. Rosato, D. Cicero, S. Pagani, M. Paci, “Surface changes and role of buried water molecules during the sulfane sulfur transfer in Rhodanese from Azotobacter vinelandii: a fluorescence quenching, 15N NMR relaxation, and nuclear magnetic relaxation dispersion spectroscopic study”. Biochemistry 42, 8550-8557 (2003). 19. S. Aime, G. Digilio, E. Bruno, V. Mainero, S. Baroni, M. Fasano, “Modulation of the antioxidant activity of HO scavengers by albumin binding: a 19F-NMR study”. Biochem. Biophys. Res. Commun. 307, 962–966 (2003). 20. M. Basso, S. Giraudo, L. Lopiano, B. Bergamasco, E. Bosticco, A. Cinquepalmi, M. Fasano. Proteome analysis of mesencephalic tissues: evidence for Parkinson’s disease. Neurol. Sci. 24, 155-156 (2003). 21. D. Corpillo, G. Gardini, A. M. Vaira, M. Basso, S. Aime, G. P. Accotto, M. Fasano, “Proteomics as a tool to assess substantial equivalence of genetically modified organisms: the case of a virus-resistant tomato”. Proteomics, 4, 193-200 (2004). 22. M. Fasano, G. Fanali, F. Polticelli, P. Ascenzi, G. Antonini, “1H-NMR relaxometric characterization of bovine lactoferrin”. J. Inorg. Biochem., 98, 1421-1426 (2004). 23. M. Fasano, A. Bocedi, M. Mattu, M. Coletta, P. Ascenzi “Nitrosylation of rabbit ferrous heme-hemopexin”. J. Biol. Inorg. Chem., 9, 800-806 (2004). 24. M. Basso, S. Giraudo, D. Corpillo, B. Bergamasco, L. Lopiano, M. Fasano, “Proteome analysis of human substantia nigra in Parkinson’s disease”. Proteomics, 4, 3943-3952 (2004). 25. A. Bocedi, S. Notari, A. Bolli, M. Fasano, P. Ascenzi, “Binding of anti-HIV drugs to human serum albumin”. IUBMB Life, 56, 609-614 (2004). 26. M. Bisaglia, I. Tessari, L. Pinato, M. Bellanda, S. Giraudo, M. Fasano, E. Bergantino, L. Bubacco, S. Mammi, “A topological model of the interaction between alphα -synucleinsand sodium dodecyl sulfate micelles”. Biochemistry, 44, 329-339 (2005). 27. P. Ascenzi, A. Bocedi, M. Fasano, M. Gioia, S. Marini, M. Coletta, “Proton-linked subunit heterogeneity in ferrous nitrosylated human adult hemoglobin: an EPR study”. J. Inorg. Biochem., 99, 1255-1259 (2005). 28. P. Ascenzi, A. Bocedi, A. Bolli, M. Fasano, S. Notari, F. Polticelli, “Allosteric modulation of monomeric proteins”. Biochem. Mol. Biol. Educ., 33, 169-176 (2005). 29. P. Ascenzi, A. Bocedi, S. Notari, E. Menegatti, M. Fasano, “Heme impairs allosterically drug binding to human serum albumin Sudlow's site I”. Biochem. Biophys. Res. Commun., 334, 481-486 (2005). 30. G. Fanali, R. Fesce, C. Agrati, P. Ascenzi, M. Fasano, “Allosteric modulation of myristate and Mn(III)heme binding to human serum albumin – Optical and NMR spectroscopy characterization”. FEBS J., 272, 4672-4683 (2005). |
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