7-BETA-HYDROPEROXYCHOLEST-5-EN-3-BETA-OL, A COMPONENT OF HUMAN ATHEROSCLEROTIC LESIONS, IS THE PRIMARY CYTOTOXIN OF OXIDIZED HUMAN LOW-DENSITY-LIPOPROTEIN

被引：197

作者：

CHISOLM, GM ^{[1
]}

MA, GP ^{[1
]}

IRWIN, KC ^{[1
]}

MARTIN, LL ^{[1
]}

GUNDERSON, KG ^{[1
]}

LINBERG, LF ^{[1
]}

MOREL, DW ^{[1
]}

DICORLETO, PE ^{[1
]}

机构：

[1] CIBA GEIGY CORP,DIV PHARMACEUT,SUMMIT,NJ 07901

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 1994年 / 91卷 / 24期

关键词：

D O I：

10.1073/pnas.91.24.11452

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Modification of low density lipoprotein (LDL) by free radical oxidation renders this molecular complex cytotoxic. Oxidized lipoproteins exist in vivo in atherosclerotic lesions and in the plasma of diabetic animals, suggesting that lipoprotein-induced tissue damage may occur in certain diseases. We undertook purification and identification of the major cytotoxin in oxidized LDL. The lipid extract from oxidized LDL was subjected to multiple HPLC separations, and the fractions were assayed for cytotoxicity. Mass spectrometry and nuclear magnetic resonance identified the purified toxin as 7 beta-hydroperoxycholest-5-en-3 beta-ol (7 beta-OOH-Chol). This molecule accounted for approximately 90% of the cytotoxicity of the lipids of oxidized LDL. We also found 7 beta-00H-Chol in human atherosclerotic lesions from endarterectomy specimens obtained immediately after excision. These results are consistent with the hypothesis that the oxidized LDL present in lesions has the capacity to induce cell and tissue injury, leading to progression of the disease and the generation of the necrotic core of the lesion.

引用

页码：11452 / 11456

页数：5

共 41 条

[1] OXIDATION OF 3-OXYGENATED DELTA(4)-C-27 AND DELTA(5)-C-27 STEROIDS BY SOYBEAN LIPOXYGENASE AND RAT-LIVER MICROSOMES [J].