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Titolo:
THE TOXICITY TO MACROPHAGES OF OXIDIZED LOW-DENSITY-LIPOPROTEIN IS MEDIATED THROUGH LYSOSOMAL DAMAGE
Autore:
YUAN XM; LI W; OLSSON AG; BRUNK UT;
Indirizzi:
LINKOPING UNIV,FAC HLTH SCI,DEPT INTERNAL MED S-58185 LINKOPING SWEDEN LINKOPING UNIV,FAC HLTH SCI,DEPT PATHOL 2 S-58185 LINKOPING SWEDEN LINKOPING UNIV,FAC HLTH SCI,CLIN RES CTR S-58185 LINKOPING SWEDEN
Titolo Testata:
Atherosclerosis
fascicolo: 2, volume: 133, anno: 1997,
pagine: 153 - 161
SICI:
0021-9150(1997)133:2<153:TTTMOO>2.0.ZU;2-Q
Fonte:
ISI
Lingua:
ENG
Soggetto:
HUMAN MONOCYTE-MACROPHAGES; CULTURED ENDOTHELIAL-CELLS; PERITONEAL-MACROPHAGES; APOLIPOPROTEIN-B; MURINE MACROPHAGES; MITOGENIC ACTIVITY; LIPID PEROXIDE; HUMAN ATHEROMA; LDL; GROWTH;
Keywords:
ATHEROSCLEROSIS; CYTOTOXICITY; LOW-DENSITY LIPOPROTEIN OXIDATION; LYSOSOMES; MACROPHAGES; OXIDATIVE STRESS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
52
Recensione:
Indirizzi per estratti:
Citazione:
X.M. Yuan et al., "THE TOXICITY TO MACROPHAGES OF OXIDIZED LOW-DENSITY-LIPOPROTEIN IS MEDIATED THROUGH LYSOSOMAL DAMAGE", Atherosclerosis, 133(2), 1997, pp. 153-161

Abstract

Oxidized low-density lipoprotein (ox-LDL) has been shown to degrade poorly within the secondary lysosomes of macrophages but its possible effect on lysosomal integrity has received less attention. The effect of ultraviolet-C oxidized LDL (UVox-LDL) on cellular viability, and lysosomal membrane stability, was examined on cultured murine J-774 cellsand human monocyte-derived macrophages (HMDMs). The acridine orange (AO) relocalization test was applied to study the lysosomal integrity of living cells. UVox-LDL dramatically reduced J-774 cell proliferationat a concentration of 25 mu g/ml. Incubation with 5 mu M copper alone, normally used to induce LDL oxidation, was also toxic. In contrast to the effects of ox-LDL, in concentrations up to 75 mu g/ml, native LDL (nLDL) rather stimulated J-774 cell replication. Incubation with UVox-LDL (25-75 mu g/ml) also altered cellular AO uptake, depending on time and dose: its lysosomal accumulation decreased and its cytosolic accumulation increased. This shift indicates damaged lysosomal membraneswith decreased intralysosomal, and increased cytosolic, Hf concentration. Many J-774 cells exposed to UVox-LDL initially transformed into foam cells and then assumed an apoptotic-type morphology with TUNEL-positive nuclei. We conclude that ox-LDL is cytotoxic to macrophages due to oxidative damage of lysosomal membranes, with ensuing destabilization and leakage to the cytosol of lysosomal contents, such as hydrolytic enzymes, causing degeneration of apoptotic type. (C) 1997 Elsevier Science Ireland Ltd.

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Documento generato il 22/02/20 alle ore 11:56:21