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Titolo:
UPTAKE OF OXIDIZED LDL BY MACROPHAGES RESULTS IN PARTIAL LYSOSOMAL-ENZYME INACTIVATION AND RELOCATION
Autore:
LI W; YUAN XM; OLSSON AG; BRUNK UT;
Indirizzi:
LINKOPING UNIV HOSP,DEPT PATHOL 2 S-58185 LINKOPING SWEDEN LINKOPING UNIV,FAC HLTH SCI,DEPT PATHOL 2 S-58183 LINKOPING SWEDEN LINKOPING UNIV,FAC HLTH SCI,DEPT INTERNAL MED S-58183 LINKOPING SWEDEN LINKOPING UNIV,FAC HLTH SCI,CLIN RES CTR S-58183 LINKOPING SWEDEN
Titolo Testata:
Arteriosclerosis, thrombosis, and vascular biology
fascicolo: 2, volume: 18, anno: 1998,
pagine: 177 - 184
SICI:
1079-5642(1998)18:2<177:UOOLBM>2.0.ZU;2-X
Fonte:
ISI
Lingua:
ENG
Soggetto:
LOW-DENSITY-LIPOPROTEIN; HUMAN MONOCYTE-MACROPHAGES; VASCULAR SMOOTH-MUSCLE; ATHEROSCLEROTIC LESIONS; ENDOTHELIAL-CELLS; APOLIPOPROTEIN-B; MODEL SYSTEM; CYTOTOXICITY; APOPTOSIS; TOXICITY;
Keywords:
ATHEROSCLEROSIS; LYSOSOMES; MACROPHAGES; OXIDIZED LDL; ANTIOXIDANTS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
49
Recensione:
Indirizzi per estratti:
Citazione:
W. Li et al., "UPTAKE OF OXIDIZED LDL BY MACROPHAGES RESULTS IN PARTIAL LYSOSOMAL-ENZYME INACTIVATION AND RELOCATION", Arteriosclerosis, thrombosis, and vascular biology, 18(2), 1998, pp. 177-184

Abstract

The cytotoxicity of oxidized LDL (oxLDL) to several types of artery wall cells might contribute to atherosclerosis by causing cell death, presumably by both apoptosis and necrosis. After its uptake into macrophage lysosomes by receptor-mediated endocytosis, oxLDL is poorly degraded, resulting in ceroid-containing loam cells. We studied the influence of oxLDL on lysosomal enzyme activity and, in particular, on lysosomal membrane stability and the modulation of these cellular characteristics by HDL and vitamin E (vit-E). Unexposed cells and cells exposed to acetylated LDL (AcLDL) were used as controls. The lysosomal marker enzymes cathepsin L, and N-acetyl-beta-glucosaminidase (NA beta Gase) were biochemically assayed in J-774 cells after fractionation. Lysosomal integrity in living cells was assayed by the acridine orange (AO) relocation test. Cathepsin D was immunocytochemically demonstrated in J-774 cells and human significantly decreased, whereas their-relative cytosolic activities were enhanced, alter oxLDL exposure. Labilization of the lysosomal membranes was further proven by decreased lysosomal AO uptake and relocation to the cytosol of cathepsin D, as estimated bylight and electron microscopic immunocytochemistry. HDL and vit-E diminished the cytotoxicity of oxLDL by decreasing the lysosomal damage. The results indicate that endocytosed oxLDL not only partially inactivates lysosomal enzymes but also destabilizes the acidic vacuolar compartment, causing relocation of lysosomal enzymes to the cytosol. Exposure to AcLDL resulted in its uptake with enlargement of the lysosomal apparatus, but the stability of the lysosomal membranes was not changed.

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Documento generato il 19/02/20 alle ore 22:27:23