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Papers of the last years

Macrophage protection against human immunodeficiency virus or herpes simplex virus by red blood cell-mediated delivery of a heterodinucleotide of azidothymidine and acyclovir. Rossi, L., Brandi, G., Schiavano, G.F., Balestra E., Millo, E., Scarfì, S., Damonte, G., Gasparini, A., Magnani, M., Perno, C-F, Benatti, U., and De Flora, A. AIDS Res. And Hum. Retrov. 14, 435- 444, 1998.

Inhibition of murine AIDS by a new azidothymidine homodinucleotide. Magnani, M., Casabianca, A., Fraternale, A., Brandi, G., Chiarantini, L., Benatti, U., Scarfì, S., Millo, E., and De Flora, A. J. Acq. Immun. Def. Syndr. and Hum. Retrov. 17, 189-195, 1998.

Cyclic GMP dependent and independent effects on the synthesis of the calcium messengers cyclic ADP-ribose and NAADP
. Graeff R.M., Franco, L., De Flora, A., and Lee, H.C. J. Biol. Chem. 273, 118-125, 1998.

Ectocellular CD38-catalyzed synthesis and intracellular Ca
mobilizing activity of Cyclic ADP-ribose. De Flora, A., Franco, L., Guida, L., Bruzzone, S., and Zocchi, E. Cell Biochem. Biophys. 28, 45-62, 1998.

Preliminary crystallographic investigations on recombinant GDP-4-keto-6-deoxy-D-mannose epimerase/reductase from coli.Tonetti, M., Rizzi, M., Vigevani, P., Sturla, L., Bisso, A., De Flora, A., and Bolognesi M. Acta Crystall. D54, 684-686, 1998.

Expression of CD38 increases intracellular calcium concentration and reduces doubling time in HeLa and 3T3 cells. Zocchi, E., Daga, A., Usai, C., Franco, L., Guida, L., Bruzzone, S., Costa, A., Marchetti, C. and De Flora, A. J. Biol. Chem. 273, 8017-8024, 1998.

The metabolism of 6-Deoxyhexoses in bacterial and animal cells.Tonetti, M., Sturla, L., Bisso, A., Zanardi, D., Benatti, U., and De Flora, A. Biochimie 80, 923-931, 1998.

Defective intracellular activity of GDP-D-mannose-4,6-dehydratase in leukocyte adhesion deficiency type II syndrome. Sturla, L., Etzioni, A., Bisso, A., Zanardi, D., De Flora, G., Silengo, L., De Flora, A., and Tonetti, M. FEBS Lett. 429, 274-278, 1998.

The transmembrane glycoprotein CD38 is a catalytically active transporter responsible for generation and influx of the second messenger cyclic ADP-ribose across membranes. Franco, L., Guida, L., Bruzzone, S., Zocchi, E., Usai, C., and De Flora, A. Faseb J. 12, 1507-1520, 1998.

Dimeric and tetrameric forms of catalytically active transmembrane CD38 in transfected HeLa cells. Bruzzone, S., Guida, L., Franco, L., Zocchi, E., Corte, G., and De Flora, A. Febs Lett. 433, 275-278, 1998.

GDP-4-keto-5-deoxy-D-mannose epimerase/reductase from coli, a key enzyme in the biosynthesis of GDP-L-fucose, displays the structural characteristics of the RED protein homology superfamily. Rizzi, M., Tonetti, M., Vigevani, P., Sturla, L., Bisso, A., De Flora, A., Bordo, D., and Bolognesi, M. Structure 6, 1453-1465, 1998.

Ligand-induced internalization of CD38 results in intracellular Ca mobilization. Role of NAD
transport across cell membranes. Zocchi, E., Usai, C., Guida, L., Franco, L., Bruzzone, S., Passalacqua, M., and De Flora, A. FASEB J. 13, 273-283, 1999.

Heterodimer-loaded erythrocytes as bioreactors for slow delivery of the antiviral drug azidothymidine and the antimycobacterial drug ethambutol. Rossi, L., Brandi, G., Schiavano, G.F., Scarfì, S., Millo, E., Damonte, G., Benatti, U., De Flora. A., and Magnani, M. AIDS Research and human retroviruses 15, 345-353, 1999.

Topology of CD38. De Flora, A., Franco, L., Guida, L., Bruzzone, S., Usai, C., and Zocchi, E. In "CD38 and related molecules" (K. Mehta and F. Malavasi, Eds.) Chem. Immunol. 75, 79-98, 2000.

Structural and enzymatic characterization of human recombinant GDP-D-mannose 4,6 dehydratase. Bisso, A., Sturla, L., Zanardi, D., De Flora, A., and Tonetti, M. FEBS Letters 456, 370-374, 1999.

Role of macrophage protection in the development of murine AIDS. Fraternale, A., Tonelli, A., Casabianca A., Vallanti, G., Chiarantini, L., Schiavano, G.F., Benatti, U., De Flora, A., and Magnani, M. J. Acquir. Immune Defic., Syndr. Hum. Retrovirol. 21, 81-89, 1999.


Extracellular cyclic ADP-ribose increases intracellular free calcium concentration and stimulates proliferation of human hemopoietic progenitors. Podestà, M., Zocchi, E., Pitto, A., Usai, C., Franco, L., Bruzzone, S., Guida, L., Bacigalupo, A., Scadden, D.T., Walseth, T.F., De Flora, A., and Daga, A. FASEB J. 14 (5), 680-690, 2000.

Probing the catalytic mechanism of GDP-4-keto-6-deoxy-D-mannose epimerase/reductase by kinetic and crystallographic characterization of site-specific mutants. Rosano, C., Bisso, A., Izzo, G., Tonetti, M., Sturla, L., De Flora, A., and M. Bolognesi. J. Mol. Biol. 303, 77-91, 2000.

Extracellular Cyclic ADP-ribose potentiates ACh-induced contraction in bovine tracheal smooth muscle via calcium mobilization. Franco, L., Bruzzone, S., Song, P., Guida, L., Zocchi, E., Walseth, T.F., Crimi, E., Usai, C., De Flora, A., and Brusasco, V. Am. J. Physiol. Lung Cell Mol. Physiol. 280, L98-L106, 2001.

Connexin 43 hemichannels mediate Ca-regulated transmembrane NAD
fluxes in intact cells. Bruzzone, S., Guida, L., Zocchi, E., Franco, L., and De Flora, A. FASEB J. 15, 10-12, 2001.

Impairment of the Golgi GDP-L-fucose transport and unresponsiveness to fucose replacement therapy in LAD II patients. Sturla, L., Puglielli, L., Tonetti, M., Berninsone, P., Hirschberg, C.B., De Flora, A., and Etzioni, A. Ped. Res. 49, 537-542, 2001.

Paracrine roles of NAD
and Cyclic ADP-ribose in increasing intracellular calcium and enhancing cell proliferation of 3T3 fibroblasts. Franco, L., Zocchi, E., Usai, C., Guida, L., Bruzzone, S., Costa, A., and De Flora, A. J. Biol. Chem. 276, 21642-21648, 2001.

Evidence of a role for Cyclic ADP-ribose in calcium signaling and neuro-transmitter release in cultured astrocytes. Verderio, C., Bruzzone, S., Zocchi, E., Fedele, E., Schenk, U., De Flora, A., and Matteoli, M. J. Neurochem. 78, 1-13, 2001.

Paracrinally stimulated expansion of early hemopoietic progenitors by stroma-generated cyclic ADP-ribose. Zocchi, E., Podestà, M., Pitto, A., Usai, C., Bruzzone, S., Franco, L., Guida, L., Bacigalupo, A., and De Flora, A. FASEB J. 15, 1610-1612, 2001.

A self-restricted CD38-connexin 43 crosstalk affects NAD
and cyclic ADP-ribose metabolism and regulates intracellular calcium in 3T3 fibroblasts. Bruzzone, S., Franco, L., Guida, L., Zocchi, E., Contini, P., Bisso, A., Usai, C., and De Flora, A. J. Biol. Chem. 276, 48300-48308, 2001.

Equilibrative and concentrative nucleoside transporters mediate influx of extracellular cyclic ADP-Ribose into 3T3 murine fibroblasts. Guida, L., Bruzzone, S., Sturla, L., Franco, L., Zocchi, E., and De Flora, A. J. Biol. Chem. 277, 47097-47105, 2002.

Cyclic ADP-ribose generation by CD38 improves human hemopoietic stem cell engraftment into NOD/SCID mice.Podestà, M., Pitto, A., Figari, O., Bacigalupo, A., Bruzzone, S., Guida, L., Franco, L., De Flora, A., and E. Zocchi. FASEB J. 17, 310-312, 2003.

Paramecium bursaria Chlorella virus 1 encodes two enzymes involved in the biosynthesis of GDP-L-fucose and GDP-D-rhamnose.
Tonetti, M., Zanardi, D., Gurnon, J.R., Fruscione, F., Armirotti, A., Damonte, G., Sturla, L., De Flora, A., and Van Etten, J.L. J. Biol. Chem. 278, 21559-21565, 2003.

Cyclic ADP-ribose is a second messenger in the lipopolysaccharide-stimulated proliferation of human blood mononuclear cells. Bruzzone, S., De Flora, A., Usai, C., Graeff, R., and Lee, H.C. Biochem. J. 375, 395-403, 2003.


Spatio-temporal propagation of Ca signals by cyclic ADP-ribose in 3T3 cells stimulated via purinergic P2Y receptors. Bruzzone, S., Kunerth, S., Zocchi, E., De Flora, A., and Guse, A.H. J. Cell Biol. 163, 837-845, 2003.

Glutamate-mediated overexpression of CD38 in astrocytes cultured with neurons. Bruzzone, S., Verderio, C., Schenk, U., Fedele, E., Zocchi, E., Matteoli. M., and De Flora. A. J. Neurochem. 89, 264-272, 2004.

Autocrine and paracrine calcium signalling by the CD38/NAD/cyclic ADP-ribose system. De Flora, A., Zocchi, E., Guida, L., Franco, L. and Bruzzone, S. Ann. N.Y. Acad. Sci. 1028, 176-191, 2004.

Concentrative influx of functionally active cyclic ADP-ribose in dimethylsulfoxide-differentiated HL-60 cells. Guida, L., Franco, L., Bruzzone, S., Sturla, L., Zocchi, E., Basile, G., Usai, C. and De Flora, A. J. Biol. Chem. 279, 22066-22075, 2004.


Concentrative uptake of cyclic ADP-ribose generated by BST
1 stroma stimulates proliferation of human hematopoietic progenitors. Podestà, M., Benvenuto, F., Pitto, A., Figari, O., Bacigalupo, A., Bruzzone, S., Guida, L., Franco, L., Paleari, L., Bodrato, N., Usai, C., De Flora, A. and Zocchi, E.. J. Biol. Chem. 280, 5343-5349, 2005.

T cell suppression mediated by mesenchymal stem cells is deficient in patients with severe aplastic anemia. Bacigalupo, A., Valle, M., Podestà, M., Pitto, A., Zocchi, E., De Flora, A., Pozzi, S., Luchetti, S., Frassoni, F., Van Lint, M.T. and Piaggio, G. Exp. Hematol. 33, 817-827, 2005.

ADP-ribosyl cyclases generate two unusual adenine homodinucleotides with cytotoxic activity on mammalian cells. Basile, G., Taglialatela-Scafati, O., Damonte, G., Armirotti, A., Bruzzone, S., Guida, L., Franco, L., Usai, C., Fattorusso, E., De Flora, A. and Zocchi, E. Proc. Natl. Acad. Sci. USA 102, 14509-14514, 2005.


Extracellular NAD regulates intracellular calcium levels and induces activazion of humangranulocytes.Bruzzone.S Moreschi,I Guida ,Usai C, Zocchi,E, De Flora A, Biochem J,393,697-704,2006.


NAADPsynthesis from 2'-phospho-cyclic ADP-ribose and nicotinic acid by ADP-ribosyl cyclases. Emerging functions of extracellular pyridine nucleotides. Moreschi, I., Bruzzone, S., Melone, L., De Flora, A. and Zocchi, E., Biochem. Biophys. Res. Commun. 345, 573-580, 2006.

Induction by 7,12-Dimethylbenz()anthracene of molecular and biochemical alterations in transformed human mammary epithelial stem cells, and protection by Acetylcysteine. De Flora, S., Scarfì, S., Izzotti, A., D'Agostini, F., Chang, C.C., Bagnasco, M., De Flora, A., Trosko, J.E. Int. J. Oncol. 29, 521-

Extracellular NAD
is an agonist of the human P2Y11 purinergic receptor in human granulocytes.Moreschi,I .,Bruzzone,S., Nicholas, R.A., Fruscione,F., Sturla, L., Benvenuto, F.,Usai,C.,Meis,S.,Kassak,M:U.,Zocchi,E.,De Flora,A.,J. Biol. Chem. 281, 31419-31429, 2006529, 2006.


Abscisic acid is an endogenous cytokine in human granulocytes with cyclic ADP-ribose as second messenger. Bruzzone, S., Moreschi, I., Usai, C., Guida, L., Damonte, G., Salis, A., Scarfì, S., Millo, E., De Flora, A., Zocchi E. Proc. Natl. Acad. Sci. USA 104, 5759-5764, 2007.

Cyclic ADP-ribose is a second messenger in the lipopolysaccharide-stimulated activation of murine N9 microglial cell line. Franco, L., Bodrato, N., Moreschi, I., Usai, C., Bruzzone, S., Scarfì, S., Zocchi, E., De Flora, A. J. Neurochem. 99, 165-176, 2006.

Emerging functions of extracellular pyridine nucleotides. Billington. R.A. Bruzzone,S.,De Flora A., GenazzaniA.A., Kohc-Nolte, F.,Ziegler M.,Zocchi,E. Mol Med,12,324-327,2006

Mitochondrial dysfunction induced by a cytotoxic adenine dinucleotide produced by ADP-ribosyl cyclases from cADPR. Bruzzone,S., Dodoni, G., Kaludercic, N., Basile, G., Millo, E., De Flora, A., Di Lisa, F., Zocchi, E. J. Biol. Chem. 282, 5045-5052, 2007.

NAADP
is an agonist of the human P2Y11 purinergic receptor. Moreschi, I., Bruzzone, S., Bodrato, N., Usai, C., Guida, L., Nicholas, R.A., Kassack, M.U., Zocchi, E., De Flora A. Cell Calcium 43, 344-355, 2008

Differential role of NADP
and NADPH in the activity and structure ofGDP-D-mannose 4,6-dehydratase from two chlorella viruses. Fruscione, F.,Sturla, L., Duncan, G., Van Etten, J.L., Valbuzzi, P., De Flora, A., Di Zanni, E., Tonetti, M. J. Biol. Chem. 283, 184-193, 2008.

Cyclic ADP-Ribose-Mediated Expansion and Stimulation of Human Mesenchymal Stem Cells by the Plant Hormone Abscisic Acid. Scarfì, S., Ferraris, C., Fruscione, F., Fresia, C., Guida, L., Bruzzone, S., Usai, C., Parodi, A., Millo, E., Salis, A., Burastero, G., De Flora, A., Zocchi, E. Stem Cells 26, 2855-2864, 2008.

Abscisic acid is an endogenous stimulator of insulin release from human pancreatic islets with cyclic-ADP ribose as second messenger. Bruzzone, S., Bodrato, N., Usai, C., Guida, L., Moreschi, I., Nano, R., Antonioli, B., Fruscione, F., Magnone, M., Scarfì, S., De Flora, A., Zocchi, E. J. Biol. Chem. 283, 32188-32197, 2008.

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., Scarfì, S., De Flora, A., Zocchi, E. J Biol. Chem. 2009 Mar 27. [Epub ahead of print]

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., Scarfì, S., Usai, C., Sturla, L., Palombo, D., De Flora, A., Zocchi, E. J Biol. Chem. 2009 Mar 30. [Epub ahead of print]


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