Pussinen Pirkko J, Metso Jari, Keva Ritva, Hirschmugl Birgit, Sattler Wolfgang, Jauhiainen Matti, Malle Ernst
Institute of Dentistry, University of Helsinki, P.O. Box 63, FIN-00014, Helsinki, Finland.
Int J Biochem Cell Biol. 2003 Feb;35(2):192-202. doi: 10.1016/s1357-2725(02)00130-9.
The two main functions of phospholipid transfer protein (PLTP) are the transfer of phospholipids between plasma lipoproteins and the conversion of high density lipoprotein (HDL), where prebeta-HDL particles are generated. HDL is considered an anti-atherogenic lipoprotein due to its function in the reverse cholesterol transport, where prebeta-HDL accepts cellular membrane cholesterol from peripheral tissues. However, the anti-atherogenic properties of native HDL may be abolished by oxidation/modification. Hypochlorous acid/hypochlorite (HOCl/OCl-)-a potent oxidant generated in vivo only by the myeloperoxidase-H2O2-chloride system of activated phagocytes-alters the physiological properties of HDL by generating a pro-atherogenic lipoprotein particle. Therefore, we have studied the effect of HOCl on the function of HDL subclass 3 (HDL3) and triglyceride-enriched HDL3 (TG-HDL3) in PLTP-mediated processes in vitro. Modification of HDL3 and TG-HDL3 with increasing HOCl concentrations (oxidant:lipoprotein molar ratio between 25:1 and 200:1) decreased the capacity of the corresponding lipoprotein particles to accept phospholipids. Although binding of PLTP to unmodified and HOCl-modified lipoprotein particles was similar, the degree of PLTP-mediated HDL conversion was decreased upon HOCl oxidation. PLTP released apolipoprotein A-I (apoA-I) from HOCl-modified HDL3, but the particles formed displayed no prebeta-mobility. Based on these findings, we conclude that the substrate properties of HOCl-modified HDL3 and TG-HDL3 in PLTP-mediated processes are impaired, which indicates that the anti-atherogenic properties of HDL are impaired.
磷脂转运蛋白（PLTP）的两个主要功能是在血浆脂蛋白之间转运磷脂以及生成前β-高密度脂蛋白（HDL）颗粒的高密度脂蛋白（HDL）的转化。由于HDL在逆向胆固醇转运中的作用，即前β-HDL从外周组织接受细胞膜胆固醇，因此被认为是一种抗动脉粥样硬化脂蛋白。然而，天然HDL的抗动脉粥样硬化特性可能会因氧化/修饰而丧失。次氯酸/次氯酸盐（HOCl/OCl-）——一种仅由活化吞噬细胞的髓过氧化物酶-H2O2-氯化物系统在体内产生的强效氧化剂——通过生成一种促动脉粥样硬化脂蛋白颗粒来改变HDL的生理特性。因此，我们研究了HOCl对体外PLTP介导过程中HDL亚类3（HDL3）和富含甘油三酯的HDL3（TG-HDL3）功能的影响。用浓度不断增加的HOCl（氧化剂与脂蛋白的摩尔比在25:1至200:1之间）修饰HDL3和TG-HDL3，会降低相应脂蛋白颗粒接受磷脂的能力。尽管PLTP与未修饰和HOCl修饰的脂蛋白颗粒的结合相似，但HOCl氧化后PLTP介导的HDL转化程度降低。PLTP从HOCl修饰的HDL3中释放载脂蛋白A-I（apoA-I），但形成的颗粒没有显示出前β迁移率。基于这些发现，我们得出结论，HOCl修饰的HDL3和TG-HDL3在PLTP介导过程中的底物特性受损，这表明HDL的抗动脉粥样硬化特性受损。
