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Titolo:
Metabolic fate of extracellular NAD in human skin fibroblasts
Autore:
Aleo, MF; Giudici, ML; Sestini, S; Danesi, P; Pompucci, G; Preti, A;
Indirizzi:
Univ Brescia, Dipartimento Sci Biomed & Biotecnol, Sez Biochim, I-25123 Brescia, Italy Univ Brescia Brescia Italy I-25123 , Sez Biochim, I-25123 Brescia, Italy Univ Siena, Dept Mol Biol, I-53100 Siena, Italy Univ Siena Siena Italy I-53100 iena, Dept Mol Biol, I-53100 Siena, Italy
Titolo Testata:
JOURNAL OF CELLULAR BIOCHEMISTRY
fascicolo: 3, volume: 80, anno: 2001,
pagine: 360 - 366
SICI:
0730-2312(2001)80:3<360:MFOENI>2.0.ZU;2-N
Fonte:
ISI
Lingua:
ENG
Soggetto:
CYCLIC ADP-RIBOSE; HUMAN ERYTHROCYTES; GLYCOHYDROLASE; CD38; CYCLASE; CELLS; DEGRADATION; TRANSPORT; HYDROLASE; ENZYME;
Keywords:
NAD; NAD-glycohydrolase; ectoenzymes; adenosine; uptake; purine; human skin fibroblasts;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
27
Recensione:
Indirizzi per estratti:
Indirizzo: Aleo, MF Univ Brescia, Dipartimento Sci Biomed & Biotecnol, Sez Biochim, Via Valsabbina 19, I-25123 Brescia, Italy Univ Brescia Via Valsabbina 19 Brescia Italy I-25123 scia, Italy
Citazione:
M.F. Aleo et al., "Metabolic fate of extracellular NAD in human skin fibroblasts", J CELL BIOC, 80(3), 2001, pp. 360-366

Abstract

Extracellular NAD is degraded to pyridine and purine metabolites by different types of surface-located enzymes which are expressed differently on theplasmamembrane of various human cells and tissues. In a previous report, we demonstrated that NAD-glycohydrolase, nucleotide pyrophosphatase and 5'-nucleotidase are located on the outer surface of human skin fibroblasts. Nucleotide pyrophosphatase cleaves NAD to nicotinamide mononucleotide and AMP,and 5'-nucleotidase hydrolyses AMP to adenosine. Cells incubated with NAD,produce nicotinamide, nicotinamide mononucleotide, hypoxanthine and adenine. The absence of ADPribose and adenosine in the extracellular compartment could be due to further catabolism and/or uptake of these products. To clarify the fate of the purine moiety of exogenous NAD, we investigated uptake of the products of NAD hydrolysis using U-[C-14]-adenine-NAD. ATP was foundto be the main labeled intracellular product of exogenous NAD catabolism; ADP, AMP, inosine and adenosine were also detected but in small quantities. Addition of ADPribose or adenosine to the incubation medium decreased uptake of radioactive purine, which, on the contrary, was unaffected by addition of inosine. ADPribose strongly inhibited the activity of ecto-NAD-hydrolyzing enzymes, whereas adenosine did not. Radioactive uptake by purine drastically dropped in fibroblasts incubated with C-14-NAD and dipyridamole, an inhibitor of adenosine transport. Partial inhibition of [C-14]-NAD uptake observed in fibroblasts depleted of ATP showed that the transport system requires ATP to some extent. All these findings suggest that adenosine is the purine form taken up by cells, and this hypothesis was confirmed incubatingcultured fibroblasts with C-14-adenosine and analyzing nucleoside uptake and intracellular metabolism under different experimental conditions. Fibroblasts incubated with [C-14]-adenosine yield the same radioactive products as with [C-14]-NAD; the absence of inhibition of [C-14]-adenosine uptake by ADPribose in the presence of alpha-beta methyleneADP, an inhibitor of 5' nucleotidase, demonstrates that ADPribose coming from NAD via NAD-glycohydrolase is finally catabolised to adenosine. These results confirm that adenosine is the NAD hydrolysis product incorporated by cells and further metabolized to ATP, and that adenosine transport is partially ATP dependent. (C) 2001 Wiley-Liss, Inc.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 02/12/20 alle ore 15:25:21