| Paracrine roles of NAD+ and cyclic ADP-ribose in increasing intracellular calcium and enhancing cell proliferation of 3T3 fibroblasts. | |
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MedLine Citation:
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PMID: 11274199 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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., Guida, L., Zocchi, E., Franco, 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 [Ca(2+)](i) levels and on proliferation of the CD38(-) target cells. CD38(+), but not CD38(-), feeder cells induced a [Ca(2+)](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-NH(2)-cADPR. Addition of recombinant ADP-ribosyl cyclase to the medium of CD38(-) feeders induced sustained [Ca(2+)](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 [Ca(2+)](i) and stimulate cell proliferation. |
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Authors:
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L Franco; E Zocchi; C Usai; L Guida; S Bruzzone; A Costa; A De Flora |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2001-03-27 |
Journal Detail:
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Title: The Journal of biological chemistry Volume: 276 ISSN: 0021-9258 ISO Abbreviation: J. Biol. Chem. Publication Date: 2001 Jun |
Date Detail:
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Created Date: 2001-06-11 Completed Date: 2001-07-19 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 2985121R Medline TA: J Biol Chem Country: United States |
Other Details:
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Languages: eng Pagination: 21642-8 Citation Subset: IM |
Affiliation:
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G. Gaslini Institute, Largo G. Gaslini 5, 16147 Genova, Italy. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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3T3 Cells ADP-ribosyl Cyclase Adenosine Diphosphate Ribose / analogs & derivatives, metabolism*, pharmacology Animals Antigens, CD* Antigens, CD38 Antigens, Differentiation / chemistry, genetics, metabolism* Binding Sites Calcium / metabolism* Cell Division / physiology* Cell Membrane / metabolism Coculture Techniques Connexin 43 / genetics, physiology Cyclic ADP-Ribose Cytosol / metabolism Kinetics Membrane Glycoproteins Mice Models, Biological Multienzyme Complexes / chemistry, metabolism NAD / metabolism* NAD+ Nucleosidase / chemistry, genetics, metabolism* Oligodeoxyribonucleotides, Antisense / pharmacology Recombinant Proteins / chemistry, metabolism Transfection |
| Chemical | |
Reg. No./Substance:
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0/Antigens, CD; 0/Antigens, Differentiation; 0/Connexin 43; 0/Membrane Glycoproteins; 0/Multienzyme Complexes; 0/Oligodeoxyribonucleotides, Antisense; 0/Recombinant Proteins; 119340-53-3/Cyclic ADP-Ribose; 20762-30-5/Adenosine Diphosphate Ribose; 53-84-9/NAD; 7440-70-2/Calcium; EC 3.2.2.5/ADP-ribosyl Cyclase; EC 3.2.2.5/Antigens, CD38; EC 3.2.2.5/Cd38 protein, mouse; EC 3.2.2.5/NAD+ Nucleosidase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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