7-BETA-HYDROPEROXYCHOLEST-5-EN-3-BETA-OL, A COMPONENT OF HUMAN ATHEROSCLEROTIC LESIONS, IS THE PRIMARY CYTOTOXIN OF OXIDIZED HUMAN LOW-DENSITY-LIPOPROTEIN
7-BETA-HYDROPEROXYCHOLEST-5-EN-3-BETA-OL, A COMPONENT OF HUMAN ATHEROSCLEROTIC LESIONS, IS THE PRIMARY CYTOTOXIN OF OXIDIZED HUMAN LOW-DENSITY-LIPOPROTEIN
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DOI：
10.1073/pnas.91.24.11452
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发表时间：
1994-11-22
影响因子：
11.1
通讯作者：
DICORLETO, PE
中科院分区：
文献类型：
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作者：
CHISOLM, GM;MA, GP;DICORLETO, PE
低密度脂蛋白(LDL)被自由基氧化修饰，使该分子复合体具有细胞毒性。氧化的脂蛋白存在于动脉粥样硬化病变和糖尿病动物的血浆中，提示脂蛋白诱导的组织损伤可能发生在某些疾病中。我们对氧化低密度脂蛋白中的主要细胞毒素进行了纯化和鉴定。氧化低密度脂蛋白的脂类提取物经过多次高效液相色谱分离，并测定其细胞毒性。经质谱学和核磁共振鉴定为7β-羟基过氧胆碱-5-烯-3-β-醇(7-β-oh-Chol)。该分子约占氧化低密度脂蛋白脂类细胞毒性的90%。我们还在动脉内膜切除术后立即获得的动脉内膜切除标本中发现了7个β-00H-CHOL。这些结果与存在于病变中的氧化低密度脂蛋白具有诱导细胞和组织损伤的能力，导致疾病的进展和病变的坏死核心的产生的假设是一致的。
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.