Seccia M, Perugini C, Bellomo G
Department of Medical Sciences, University of Torino, Novara, Italy.
Biochem Biophys Res Commun. 1997 Mar 27;232(3):613-7. doi: 10.1006/bbrc.1997.6148.
NO and NO-donors are able to inhibit the peroxidation of polyunsaturated fatty acids in human low-density lipoproteins (LDL) exposed to Cu+2. Here we report that 1-hydroxy-2-oxo-3,3-bis(3-aminoethyl)-1-triazene (NOC-18), a compound which releases NO at low rate in aqueous solutions, powerfully inhibits the peroxidation of polyunsaturated fatty acids, tryptophan loss, the formation of fluorescent aldehydic adducts in apo B100 and the increase of electrophoretic mobility in isolated LDL undergoing oxidation. The inhibitory effect is not restricted to Cu+2-induced peroxidation but is also detectable with other oxidizing conditions such as the free radical generator 2,2'-azobis-(2-amidino propane) hydrochloride (AAPH), the combination of horseradish peroxidase and H2O2 (HRP), and peroxynitrite (ONOO-). The recognition of Cu+2-, AAPH-, and ONOO(-)-modified LDL by specific autoantibodies present in serum of atherosclerotic patients is almost completely inhibited when the oxidation procedure is performed in the presence of NOC-18. However, NOC-18 is completely ineffective in preventing the formation of recognizable antigens in HRP-modified LDL. These findings suggest that NO may efficiently prevent the formation of some, but not all, the antigenic epitopes recognized by human autoantibodies and thus likely formed during in vivo LDL oxidation.
一氧化氮（NO）及NO供体能够抑制暴露于Cu²⁺的人低密度脂蛋白（LDL）中多不饱和脂肪酸的过氧化反应。在此我们报告，1-羟基-2-氧代-3,3-双（3-氨乙基）-1-三氮烯（NOC-18），一种在水溶液中缓慢释放NO的化合物，能有效抑制多不饱和脂肪酸的过氧化反应、色氨酸损失、载脂蛋白B100中荧光醛加合物的形成以及氧化过程中分离的LDL电泳迁移率的增加。这种抑制作用不仅限于Cu²⁺诱导的过氧化反应，在其他氧化条件下也可检测到，如自由基引发剂2,2'-偶氮双（2-脒基丙烷）盐酸盐（AAPH）、辣根过氧化物酶与H₂O₂的组合（HRP）以及过氧亚硝酸盐（ONOO⁻）。当在NOC-18存在下进行氧化过程时，动脉粥样硬化患者血清中存在的特异性自身抗体对Cu²⁺、AAPH和ONOO⁻修饰的LDL的识别几乎被完全抑制。然而，NOC-18在防止HRP修饰的LDL中形成可识别的抗原方面完全无效。这些发现表明，NO可能有效地阻止了人体内自身抗体识别的部分而非全部抗原表位的形成，因此这些抗原表位可能是在体内LDL氧化过程中形成的。
