Biochemistry

Director: Edon Melloni
Full Professor

Major Research Line

  • Cloning, expression and biochemical characterization of Ca2+-dependent proteolytic system proteins. (Edon Melloni)
    Our research is focused on the regulation mechanism of calpain/calpastatin system , particularly on the modification of expression levels and of activities about the different isoforms of the protease and its natural inhibitor in different pathological conditions as inflammation or neurodegenerative diseases. Now we study the implication of calpain in inflammation, because in this conditions a dis-regulation of calpain might occur, producing an abnormal cell migration, adhesion and motility, involved in the early phase of atherosclerotic process.
    The possibility to restore calpain regulation process reducing the extent of cells undergoing to permanent modifications will be explored. Previous attempts to replace the consumed calpastatin with synthetic inhibitors did not give exiting results due to their low specificity. We have in aim to modify the calpastatin efficiency through cellular post-translational modification such as phosphorylation PKA or PKC. Over-expression of this protein is an other possibility. Finally we can produce calpastatin fragments retaining the calpain consensus sequence and two short flanking sequences to use as mini calpastatins. We have just synthesized a 20-residue peptide expressing a good calpain inhibition.

  • Extracellular functions of HMGB1 protein in mammalian cells and tissues (Bianca Sparatore)
    Identification of extracellular functions of HMGB1 on cells of the vascular system. This specific purpose will be pursued using recombinant forms of HMGB1 (wild-type and mutated) and endothelial cells of macrovascular and microvascular origin from human, bovine and murine sources, as targets.
    The following parameters will be measured
    1) cell proliferation, chemotaxis, invasion, morphogenesis and protease production in phenotypes with or without the receptor for the advanced glycation end products (RAGE), proposed as one of the most widely expressed sites for HMGB1 recognition on the external cell surface;
    2) activation of the intracellular cascades of signal transduction including MAPK, PLC-gamma/protein kinase C, little G proteins of the Rho family;
    3) changes in the gene expression profile;
    4) changes in the proteome of whole cells.

    Role of extracellular HMGB1 in human carcinoma, mesothelioma and glioma cell lines which express or do not express RAGEas well as in cortical primary astrocytes. The release of HMGB1 from these cells will be measured at first in the absence or the presence of growth factors, phorbol esters or steroid hormones.

    Wild-type and mutant HMGB1 forms will be then tested for their ability in modulating
    1) cell proliferation, motility, invasive potential;
    2) activation of intracellular cascades of signal transduction in the absence or the presence of sub-optimal or optimal concentrations of other prototypic stimuli;
    3) calcium dependent biochemical systems.

Publications

  • J. Biol. Chem. (2009)
    Abscisic acid activates the murine microglial cell line N9 through the second messenger cyclic ADP-ribose
    Bodrato, N., Franco, L., Fresia, C., Guida, L., Usai, C., Salis, A., Moreschi, I., Ferraris, C., Verderio, C., Basile, G., Bruzzone, S., Scarf?, S., De Flora, A., Zocchi, E.
    284(22):14777-14787
  • J. Biol. Chem. (2009)
    Abscisic acid released by human monocytes activates monocytes and vascular smooth muscle cell responses involved in atherogenesis.
    Magnone, M., Bruzzone, S., Guida, L., Damonte, G., Millo, E., Scarf?, S., Usai, C., Sturla, L., Palombo, D., De Flora, A., Zocchi, E.
    284(26):17808-17818
  • J. Biol. Chem. (2009)
    P2X7-mediated increased intracellular calcium causes functional derangement in Schwann cells from rats with CMT1A neuropathy
    Nobbio, L., Sturla, L., Fiorese, F., Usai, C., Basile, G., Moreschi, I., Benvenuto, F., Zocchi, E., De Flora, A., Schenone, A., Bruzzone, S. , .
    284(34):23146-58
  • J. Biol. Chem. (2009)
    LANCL2 is necessary for Abscisic acid binding and signaling in human granulocytes and in rat insulinoma cells
    Sturla, L., Fresia, C., Guida, L., Bruzzone, S., Scarf?, S., Usai, C., Fruscione, F., Magnone, M., Millo, E., Basile, G., Grozio, A., Jacchetti, E., Allegretti, M., De Flora, A., Zocchi, E.
    284(41):28045-57
  • Stem Cells (2009)
    The plant hormone Abscisic acid stimulates the proliferation of human hemopoietic progenitors through the second messenger cyclic ADP-Ribose.
    Scarf?, S., Fresia, C., Ferraris, C., Bruzzone, S., Fruscione, F., Usai, C., Benvenuto, F., Magnone, M., Podest?, M., Sturla, L., Guida, L., Albanesi, E., Damonte, G., Salis, A., De Flora, A., Zocchi, E.
    27(10):2469-77
  • PLoS One (2009)
    Catastrophic NAD+ depletion in activated T lymphocytes through Nampt inhibition reduces demyelination and disability in EAE
    Bruzzone, S., Fruscione, F., Morando, S., Ferrando, T., Poggi, A., Garuti, A., D'Urso, A., Selmo, M., Benvenuto, F., Cea, M., Zoppoli, G., Moran, E., Soncini, D., Ballestrero, A., Sordat, B., Patrone, F., Mostoslavsky, R., Uccelli, A., Nencioni, A. ,
    4(11):e7897
  • In Vitro Cell Dev. Biol. Anim. (2009)
    Influence of rocky substrata on three-dimensional sponge cells model development
    Pozzolini, M., Valisano, L., Cerrano, C., Menta, M., Schiaparelli, S., Bavestrello, G., Benatti, U., Giovine, M.

  • J. Proteome Res (2009)
    Primary structure and post-translational modifications of silicatein beta from the marine sponge Petrosia ficiformis (Poiret, 1789)
    Armirotti, A., Damonte, G., Pozzolini, M., Mussino, F., Cerrano, C., Salis, A., Benatti, U., Giovine, M.
    8(8):3995-4004
  • Respir. Res. (2009)
    Ascorbic acid pre-treated quartz stimulates TNF-alpha release in RAW 264.7 murine macrophages through ROS production and membrane lipid peroxidation
    Scarf?, S., Magnone, M., Ferraris, C., Pozzolini, M., Benvenuto, F., Benatti, U., Giovine, M.
    0,43402777778
  • Rapid. Commun. Mass Spectrom. (2009)
    Top-down proteomics with a quadrupole time-of-flight mass spectrometer and collision-induced dissociation
    Armirotti, A., Benatti, U., Damonte, G.
    23(5):661-6
  • THE JOURNAL OF BIOLOGICAL CHEMISTRY( J.B.C). (2007)
    Regulation of calpain activity in rat brain with altered CA2+ homeostasis
    AVERNA M, STIFANESE R, DE TULLIO R, PASSALACQUA M, DEFRANCHI E, SALAMINO F., MELLONI E, PONTREMOLI S. . ISSN: 0021-9258
    vol. 282(4), pp. 2656--2665
  • THE JOURNAL OF BIOLOGICAL CHEMISTRY( J.B.C). (2006)
    "Association of calpastatin with inactive calpain: a novel mechanism to control the activation of the protease . ISSN: 0021-9258 "
    MELLONI E., AVERNA M, STIFANESE R, DE TULLIO R, SALAMINO F, AND PONTREMOLI S
    vol.281, pp.24945-24954
  • JOURNAL OF NEUROCHEMISTRY.ISSN: 0022-3042 (2006)
    "Stimulation of excitatory amino acid release from adult mouse brain glia subcellular particles by high mobility group box-1 protein . "
    PEDRAZZI M, RAITERI L, BONANNO G, PATRONE M, LEDDA S, PASSALACQUA M, MILANESE M, MELLONI E., RAITERI M, PONTREMOLI S, SPARATORE B
    vol. 99, pp. 827-838
  • FEBS Journal (2006)
    "Interaction between catalytically inactive calpain and calpastatin: evidence for its occurrence in stimulated cells "
    Averna, M., Stifanese R., De Tullio, R., Defranchi E., Salamino, F., Melloni,E. and Pontremoli,S.
    vol.273, 1660-1668
  • Biochem.Journal (2005)
    "Activation of A431 human carcinoma cell motilit? by extracellular high mobility proup box 1 prtoein and epidermal growth factor stimuli. - "
    Sparatore B., Patrone,M., Passalacqua,M., Pedrazzi,M., Ledda,S., Pontremoli,S., Melloni,E.
    vol.389, pp.215-221

Staff

Name Surname Qualification Unit Contacts
Monica. Averna . recipient of research contract . Biochemistry.
monicaaverna@hotmail.it
103538157
Roberta. De Tullio. Researcher . Biochemistry.
detullio@unige.it
103538157
Edon. Melloni. Full Professor . Biochemistry.
melloni@unige.it
103538128
Mario. Passalacqua . Researcher . Biochemistry.
passama@unige.it
103538219
Marco. Pedrazzi . co.co.co . Biochemistry.
marcopedraz@libero.it
103538219
Franca. Salamino . Full Professor . Biochemistry.
salamino@unige.it
203538160
Bianca. Sparatore. Full Professor. Biochemistry.
traspar@unige.it
103538160
Roberto. Stifanese. recipient of research contract. Biochemistry.
stifanese@unige.it
103538157

Collaborations

Internazionali

Columbia University,New York, NY, USA (Prof. Dave Stern)
Department Human Genetics, Sackler School of Medicine, Tel Aviv University, Israel (Prof. Kosower,N.S., Dott. Barnoy,S., Gloser,T.)
Biological Research Center, Hungarian Academy of Sciences, Budapest (Prof. Friederich,P.)
Ottawa Health Research Institute, University of Ottawa, (prof. Park) ;

Nazionali

Dipartimento di Chimica Biologica, Universit? di Padova (Prof. Fabio di Lisa)
International Institute of genetics and Biophysic of CNR Naples (prof. Mita)
Dipartimento di Scienze Biomediche, Universit? di Teramo
Dipartimento di Fisica Facolt? di Ingegneria Universit? di Trento (prof.Antolini )
Universit? degli studi di Brescia (prof. Marco Presta)
Dip. Chimica, Biochimica e Biotecnologie per la Medicina, Universit? degli studi di Milano ( Prof. Riboni)
Universit? degli Studi di Torino (Prof. Bussolino)

Bact to units list

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