Catalogo Articoli (Spogli Riviste)

OPAC HELP

Titolo:
THE IMMUNOSUPPRESSIVE SUBSTANCE 2-CHLORO-2-DEOXYADENOSINE MODULATES LIPOPROTEIN METABOLISM IN A MURINE MACROPHAGE CELL-LINE (P388 CELLS)
Autore:
LECHLEITNER M; AUER B; ZILIAN U; HOPPICHLER F; SCHIRMER M; FOGER B; GEISEN F; PATSCH JR; KONWALINKA G;
Indirizzi:
INNSBRUCK UNIV,DEPT INTERNAL MED,ANICHSTR 35 A-6020 INNSBRUCK AUSTRIA INNSBRUCK UNIV,DEPT BIOCHEM A-6020 INNSBRUCK AUSTRIA
Titolo Testata:
Lipids
fascicolo: 9, volume: 29, anno: 1994,
pagine: 627 - 633
SICI:
0024-4201(1994)29:9<627:TIS2ML>2.0.ZU;2-1
Fonte:
ISI
Lingua:
ENG
Soggetto:
LOW-DENSITY-LIPOPROTEIN; HUMAN MONOCYTE-MACROPHAGES; SCAVENGER-RECEPTOR; HUMAN-LYMPHOCYTES; FOAM CELLS; 2-CHLORODEOXYADENOSINE; TOXICITY; CHOLESTEROL; INVITRO; ESTER;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
34
Recensione:
Indirizzi per estratti:
Citazione:
M. Lechleitner et al., "THE IMMUNOSUPPRESSIVE SUBSTANCE 2-CHLORO-2-DEOXYADENOSINE MODULATES LIPOPROTEIN METABOLISM IN A MURINE MACROPHAGE CELL-LINE (P388 CELLS)", Lipids, 29(9), 1994, pp. 627-633

Abstract

A recently developed immunosuppressive substance, 2-chloro-2-deoxyadenosine (2-CdA), was reported to inhibit monocyte functions at low concentration. Because macrophages play a key role in the formation of atherosclerotic plaques, it was of interest to study the effect of 2-CdA on cellular lipid metabolism. For this purpose we have used a macrophage cell line (P388) to perform incubation studies in the presence of acetylated low density lipoprotein (Ac-LDL) and 2-CdA. The addition of 2-CdA, in concentrations ranging from 5-20 nM, induced a dose-dependent decrease in cellular cholesterol content and in the amount of extracellular [C-14]oleic acid (OA) incorporated into the cholesteryl ester (CE) fraction. The effect was maximized at 20 nM 2-CdA with an 86% reduction in cholesterol esterification compared to controls (P < 0.008). To evaluate the mechanism of interaction of 2-CdA with cellular lipidmetabolism, deoxycytidine (dCyt) and 3-methoxybenzamide (3-MOB), substances known to antagonize the effect of 2-CdA in different ways, wereco administered with 2-CdA. dCyt, a competitive inhibitor of dCyt kinase, which catalyzes phosphorylation to the active metabolite, antagonized the effects of 20 nM 2-CdA, producing significantly greater incorporation of extracellular [C-14]OA into the CE fraction than in the presence of 2-CdA alone (P < 0.0086). Co-incubation with 2-CdA and the poly-ADP-ribose synthetase inhibitor 3-MOB, which is known to render cells resistant to 2-CdA toxicity by preventing cellular nicotinamide adenine dinucleotide (NAD)- and adenosine triphosphase-depletion, also reversed the effect of 2-CdA on lipid accumulation. However, incubationof P388 cells with 20 nM 2-CdA did not result in a decrease in cellular NAD content. As 20 nM 2-CdA showed no effect on intracellular cholesterol synthesis based on measurement by 3-hydroxy-3-methylglutaryl coenzyme A reductase activity, the decrease in cellular cholesterol content and in [C-14]OA incorporation seems to be primarily due to an interference with Ac-LDL metabolism.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 31/03/20 alle ore 16:18:01