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Titolo:
Paracrine roles of NAD(+) and cyclic ADP-ribose in increasing intracellular calcium and enhancing cell proliferation of 3T3 fibroblasts
Autore:
Franco, L; Zocchi, E; Usai, C; Guida, L; Bruzzone, S; Costa, A; De Flora, A;
Indirizzi:
Univ Genoa, Dept Expt Med, Biochem Sect, I-16132 Genoa, Italy Univ Genoa Genoa Italy I-16132 t Med, Biochem Sect, I-16132 Genoa, Italy G Gaslini Inst, I-16147 Genoa, Italy G Gaslini Inst Genoa Italy I-16147G Gaslini Inst, I-16147 Genoa, Italy CNR, Inst Cybernet & Biophys, I-16149 Genoa, Italy CNR Genoa Italy I-16149 R, Inst Cybernet & Biophys, I-16149 Genoa, Italy Ist Nazl Studio & Cura Tumori, Dept Expt Oncol, I-20133 Milan, Italy Ist Nazl Studio & Cura Tumori Milan Italy I-20133 , I-20133 Milan, Italy
Titolo Testata:
JOURNAL OF BIOLOGICAL CHEMISTRY
fascicolo: 24, volume: 276, anno: 2001,
pagine: 21642 - 21648
SICI:
0021-9258(20010615)276:24<21642:PRONAC>2.0.ZU;2-Q
Fonte:
ISI
Lingua:
ENG
Soggetto:
HUMAN CD38; DOUBLING TIME; CYCLASE; EXPRESSION; RADIOIMMUNOASSAY; CATALYZE; PROTEIN; BINDING;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
34
Recensione:
Indirizzi per estratti:
Indirizzo: De Flora, A Univ Genoa, Dept Expt Med, Biochem Sect, Viale Benedetto XV 1,I-16132 Genoa, Italy Univ Genoa Viale Benedetto XV 1 Genoa Italy I-16132 oa, Italy
Citazione:
L. Franco et al., "Paracrine roles of NAD(+) and cyclic ADP-ribose in increasing intracellular calcium and enhancing cell proliferation of 3T3 fibroblasts", J BIOL CHEM, 276(24), 2001, pp. 21642-21648

Abstract

CD38 is a bifunctional ectoenzyme synthesizing from NAD(+) (ADP-ribosyl cyclase) and degrading (hydrolase) cyclic ADP-ribose (cADPR), a powerful universal calcium mobilizer from intracellular stores. Recently, hexameric connexin 43 (Cx43) hemichannels have been shown to release cytosolic NAD(+) from isolated murine fibroblasts (Bruzzone, S., Guide, L., Zocchi, E., France,L. and De Flora, A. (2001) FASEB J. 15, 10-12), making this dinucleotide available to the ectocellular active site of CD38. Here we investigated transwell co-cultures of CD38(+) (transfected) and CD38(-) 3T3 cells in order to establish the role of extracellular NAD(+) and cADPR on [Ca2+](i) levels and on proliferation of the CD38(-) target cells. CD38(+), but not CD38(-),feeder cells induced a [Ca2+](i) increase in the CD38(-) target cells which was comparable to that observed with extracellular cADPR alone and inhibitable by NAD(+)-glycohydrolase or by the cADPR antagonist 8-NH2-cADPR. Addition of recombinant ADP-ribosyl cyclase to the medium of CD38(-) feeders induced sustained [Ca2+](i) increases in CD38(-) target cells. Co-culture on CD38(+) feeders enhanced the proliferation of CD38(-) target cells over control values and significantly shortened the S phase of cell cycle. These results demonstrate a paracrine process based on Cx43-mediated release of NAD(+), its CD38-catalyzed conversion to extracellular cADPR, and influx of this nucleotide into responsive cells to increase [Ca2+](i) and stimulate cell proliferation.

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Documento generato il 18/09/20 alle ore 17:54:18