Napoli C, Ambrosio G, Palumbo G, Elia P P, Chiariello M
Cattedra di Cardiologia, II Facoltà di Medicina e Chirurgia, Università degli Studi, Napoli.
Cardiologia. 1991 Jul;36(7):527-32.
Low-density lipoproteins (LDL) oxidized by oxygen radicals (OR) are a potent atherogenic stimulus. Chemically modified LDL are internalized by macrophages via a specific cell surface receptor that was termed the scavenger receptor, and may induce foam cells transformation. A free radical is any chemical species that has an unpaired electron. This property renders it highly chemically reactive. When a radical reacts with a non radical another free radical is generated. This characteristic enables radicals to trigger chain reactions. Oxygen radicals are: superoxide anion (.O2-), hydroxyl radical (.OH) and hydrogen peroxide (H2O2). It is unknown whether LDL are modified via direct lipid oxidation by OR, or whether LDL are subsequently oxidized via chain reactions after initial OR attack. To distinguish between these 2 mechanisms, LDL were exposed to OR formed by xanthine/xanthine oxidase (X/XO). Peroxidation was measured from malonyldialdehyde (MDA) levels. Parallel experiments were performed in presence of the superoxide radical scavenger superoxide dismutase (SOD; 330 U/ml), or the hydrogen peroxide scavenger catalase (CAT; 1000 U/ml), or by adding the chain-reaction inhibitor butylhydroxytoluene (BHT; 1 mM) at selected time points. SOD, but not CAT prevented LDL peroxidation, indicating an obligatory role for superoxide radicals. Superoxide generation in this model lasts only a few minutes, however, MDA levels continued to increase over several hours. Furthermore, this phenomenon was blocked when BHT was added at various times after X/XO. These data show that LDL peroxidation is triggered by initial OR generation but then involves chain reactions which do not require continuous exposure to OR.(ABSTRACT TRUNCATED AT 250 WORDS)
被氧自由基（OR）氧化的低密度脂蛋白（LDL）是一种强大的致动脉粥样硬化刺激物。化学修饰的LDL通过一种被称为清道夫受体的特定细胞表面受体被巨噬细胞内化，并可能诱导泡沫细胞转化。自由基是任何具有未配对电子的化学物质。这种性质使其具有高度的化学反应性。当一个自由基与一个非自由基反应时，会产生另一个自由基。这种特性使自由基能够引发链式反应。氧自由基包括：超氧阴离子（·O₂⁻）、羟基自由基（·OH）和过氧化氢（H₂O₂）。目前尚不清楚LDL是通过OR直接脂质氧化进行修饰，还是在OR最初攻击后通过链式反应随后被氧化。为了区分这两种机制，将LDL暴露于由黄嘌呤/黄嘌呤氧化酶（X/XO）形成的OR中。通过丙二醛（MDA）水平测量过氧化作用。在超氧自由基清除剂超氧化物歧化酶（SOD；330 U/ml）或过氧化氢清除剂过氧化氢酶（CAT；1000 U/ml）存在的情况下，或在选定时间点添加链式反应抑制剂丁基羟基甲苯（BHT；1 mM）进行平行实验。SOD而非CAT可防止LDL过氧化，表明超氧自由基起关键作用。然而，该模型中超氧自由基的产生仅持续几分钟，而MDA水平在数小时内持续升高。此外，在X/XO后不同时间添加BHT时，这种现象被阻断。这些数据表明，LDL过氧化由最初的OR产生引发，但随后涉及不需要持续暴露于OR的链式反应。（摘要截短于250词）
