Seccia M, Perugini C, Albano E, Bellomo G
Department of Medical Sciences, University of Torino, Novara, Italy.
Biochem Biophys Res Commun. 1996 Mar 18;220(2):306-9. doi: 10.1006/bbrc.1996.0401.
The incubation of low density lipoproteins with Cu++ promotes oxidative modifications that make them atherogenic. Comparable alterations occur in vivo and are modulated by the generation of nitric oxide by endothelial cells or macrophages. Here we report that two donors (NOC-9 and NOC-18) with different half times of NO release (2.7 and >500 min, respectively) inhibit in vitro lipoprotein oxidation promoted by Cu++. Both donors increase the duration of the lag-phase and decrease the maximum rate of conjugated diene formation, prevent the loss of tryptophan in Apo B100, and decrease the formation of fluorescent adducts. The protective effect of NOC-9 was rapidly exhausted and its overall efficacy in preventing LDL oxidation was two orders of magnitude lower than that exhibited by NOC-18. These findings suggest that a continuous flux of NO generation, even at lower concentrations, is more efficient than considerably higher doses released as a burst in protecting both the lipid and the protein moiety of LDL from oxidation.
低密度脂蛋白与Cu++温育会促进氧化修饰，使其具有致动脉粥样硬化性。体内会发生类似变化，且受内皮细胞或巨噬细胞产生一氧化氮的调节。在此我们报告，两种半衰期不同的一氧化氮供体（NOC - 9和NOC - 18，半衰期分别为2.7分钟和>500分钟）可抑制Cu++促进的体外脂蛋白氧化。两种供体均延长了滞后期的持续时间，降低了共轭二烯形成的最大速率，防止载脂蛋白B100中色氨酸的损失，并减少了荧光加合物的形成。NOC - 9的保护作用迅速耗尽，其在预防低密度脂蛋白氧化方面的总体功效比NOC - 18低两个数量级。这些发现表明，即使在较低浓度下，持续产生的一氧化氮通量在保护低密度脂蛋白的脂质和蛋白质部分免受过氧化方面比以突发形式释放的高得多的剂量更有效。
