Noto H, Hashimoto Y, Satoh H, Hara M, Iso-o N, Togo M, Kimura S, Tsukamoto K
Department of Metabolic Diseases, University of Tokyo, Tokyo, Japan.
Biochem Biophys Res Commun. 2001 Nov 30;289(2):395-401. doi: 10.1006/bbrc.2001.5985.
Paraoxonase1 (PON1) is a high-density lipoprotein (HDL)-associated protein which removes peroxidized lipids from lipoproteins. It has been proposed that apolipoprotein A-I (apoA-I) is an important determinant for its stabilization on HDL. However, little is known about its existence and activity in an apoA-I-deficient state in humans. To characterize the nature of PON1 in apoA-I deficiency, we investigated PON1 in an apoA-I-deficient patient. When serum was analyzed on fast protein liquid chromatography, PON1 protein was distributed almost exclusively on HDL despite the absence of apoA-I; on the other hand, 38.5% of PON1 protein was found in the lipoprotein-free fraction when the lipoproteins were fractionated through ultracentrifugation. The stability of PON1 activity in the patient serum was almost the same as in the normal control sera throughout incubation at 14 degrees C for 7 days. However, when the sera were incubated at 37 degrees C for 24 h, its activity declined more than those in the normal controls (19% versus 4% reduction of the initial values). Our results demonstrated that PON1 protein possesses a preferential association with HDL even in the absence of apoA-I, although apoA-I is a crucial factor for the maximal activity and stabilization of PON1.
对氧磷酶1(PON1)是一种与高密度脂蛋白(HDL)相关的蛋白质,可从脂蛋白中去除过氧化脂质。有人提出,载脂蛋白A-I(apoA-I)是其在HDL上稳定存在的重要决定因素。然而,关于其在人类apoA-I缺乏状态下的存在和活性知之甚少。为了表征apoA-I缺乏时PON1的性质,我们对一名apoA-I缺乏患者的PON1进行了研究。当通过快速蛋白质液相色谱分析血清时,尽管缺乏apoA-I,但PON1蛋白几乎完全分布在HDL上;另一方面,当通过超速离心对脂蛋白进行分级分离时,发现38.5%的PON1蛋白存在于无脂蛋白组分中。在14℃下孵育7天的整个过程中,患者血清中PON1活性的稳定性与正常对照血清几乎相同。然而,当血清在37℃下孵育24小时时,其活性下降幅度大于正常对照(初始值分别降低19%和4%)。我们的结果表明,即使在没有apoA-I的情况下,PON1蛋白也与HDL具有优先结合,尽管apoA-I是PON1最大活性和稳定性的关键因素。