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Titolo:
TOXICITY OF OXYSTEROLS TO HUMAN MONOCYTE-MACROPHAGES
Autore:
CLARE K; HARDWICK SJ; CARPENTER KLH; WEERATUNGE N; MITCHINSON MJ;
Indirizzi:
UNIV CAMBRIDGE,DEPT PATHOL,DIV CELLULAR PATHOL,TENNIS COURT RD CAMBRIDGE CB2 1QP ENGLAND UNIV CAMBRIDGE,DEPT PATHOL,DIV CELLULAR PATHOL CAMBRIDGE CB2 1QP ENGLAND
Titolo Testata:
Atherosclerosis
fascicolo: 1, volume: 118, anno: 1995,
pagine: 67 - 75
SICI:
0021-9150(1995)118:1<67:TOOTHM>2.0.ZU;2-H
Fonte:
ISI
Lingua:
ENG
Soggetto:
LOW-DENSITY-LIPOPROTEIN; SMOOTH-MUSCLE CELLS; OXYGENATED STEROLS; CHOLESTEROL DEPOSITION; BIOLOGICAL-ACTIVITIES; BINDING-SITE; INVITRO; ATHEROSCLEROSIS; OXIDATION; 25-HYDROXYCHOLESTEROL;
Keywords:
OXYSTEROL; CYTOTOXICITY; MONOCYTE-MACROPHAGES (HUMAN); ATHEROSCLEROSIS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
46
Recensione:
Indirizzi per estratti:
Citazione:
K. Clare et al., "TOXICITY OF OXYSTEROLS TO HUMAN MONOCYTE-MACROPHAGES", Atherosclerosis, 118(1), 1995, pp. 67-75

Abstract

We have investigated the toxicity of the cholesterol oxidation products (oxysterols), 7 alpha-hydroxycholesterol, 7 beta-hydroxycholesterol, 7-ketocholesterol, 25-hydroxycholesterol and 26-hydroxycholesterol to human monocyte-macrophages in vitro. The 7-position derivatives are present in low density lipoprotein (LDL) oxidised with copper (II) sulphate and by macrophages, and in extracts of human atherosclerotic lesions, which also contain 26-hydroxycholesterol. We have also assessed 25-hydroxycholesterol for toxicity because it has often been used in studies of 3-hydroxy-3-methyl-glutaryl-CoA (HMG-CoA) reductase inhibition and LDL receptor down-regulation. Measurement of radioactivity release from monocyte-macrophages preloaded with tritiated adenine, as a means of assessing cytotoxicity, indicated that all the oxysterols showed time- and concentration-dependent toxicity: The cytotoxic potency of 26-hydroxycholesterol was the greatest. The 7-position derivatives also produced marked cell damage, though at higher concentrations than for 26-hydroxycholesterol. Of the oxysterols assessed, the toxicity of25-hydroxycholesterol was the least. The cytotoxicity of 7 beta-hydroxycholesterol and 26-hydroxycholesterol was also shown using the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) dye reduction assay which confirmed that 26-hydroxycholesterol was more toxicthan 7 beta-hydroxycholesterol. Incubation of monocyte-macrophages with cholesterol added to the different oxysterols gave varying results. Cholesterol, which was not itself toxic, inhibited the toxicity of 25-hydroxycholesterol and 26-hydroxycholesterol, but the toxicity of the7-position derivatives was not affected. The possible relevance of these molecules to the death of macrophages seen in atherosclerosis is discussed.

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Documento generato il 26/02/20 alle ore 06:07:56