Document Detail

ADP-ribosyl cyclases generate two unusual adenine homodinucleotides with cytotoxic activity on mammalian cells.
MedLine Citation:
PMID:  16172408     Owner:  NLM     Status:  MEDLINE    
ADP-ribosyl cyclases are ubiquitous enzymes responsible for synthesis from NAD(+) of the intracellular calcium-releasing signal molecules cyclic ADP-ribose (cADPR) and nicotinic acid adenine dinucleotide phosphate (NAADP(+)). Here, we show that cyclases from lower and higher Metazoa also synthesize three adenylic dinucleotides from cADPR and adenine: diadenosine diphosphate and two isomers thereof. These dinucleotides are present and metabolized in mammalian cells and affect intracellular calcium and cell proliferation. The diadenosine diphosphate isomers are naturally occurring nucleotides containing an N-glycosidic bond different from the usual C1'-N9. The identification of these members of the family of NAD(+)-derived, calcium-active nucleotides opens new areas of investigation into their functional cooperation with cADPR and NAADP(+) and into their involvement in the physiology and pathology of calcium-controlled cell functions.
Giovanna Basile; Orazio Taglialatela-Scafati; Gianluca Damonte; Andrea Armirotti; Santina Bruzzone; Lucrezia Guida; Luisa Franco; Cesare Usai; Ernesto Fattorusso; Antonio De Flora; Elena Zocchi
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't     Date:  2005-09-19
Journal Detail:
Title:  Proceedings of the National Academy of Sciences of the United States of America     Volume:  102     ISSN:  0027-8424     ISO Abbreviation:  Proc. Natl. Acad. Sci. U.S.A.     Publication Date:  2005 Oct 
Date Detail:
Created Date:  2005-10-12     Completed Date:  2006-04-20     Revised Date:  2013-06-07    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  United States    
Other Details:
Languages:  eng     Pagination:  14509-14     Citation Subset:  IM    
Department of Experimental Medicine, Section of Biochemistry, University of Genoa, Viale Benedetto XV 1, 16132 Genoa, Italy.
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MeSH Terms
ADP-ribosyl Cyclase / metabolism*
Adenine Nucleotides / biosynthesis*
Calcium / metabolism
Cell Proliferation / drug effects
Cyclic ADP-Ribose / metabolism*
Dinucleoside Phosphates / biosynthesis*,  chemistry,  toxicity
HeLa Cells
Porifera / chemistry*
Protein Isoforms / toxicity
Reg. No./Substance:
0/Adenine Nucleotides; 0/Dinucleoside Phosphates; 0/Protein Isoforms; 119340-53-3/Cyclic ADP-Ribose; 7440-70-2/Calcium; EC Cyclase
Comment In:
Proc Natl Acad Sci U S A. 2005 Oct 18;102(42):14941-2   [PMID:  16217035 ]

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