Departament de Farmacologia, Universitat de València, València, Spain.
Departament de Farmacologia. Universitat de València, Facultat de Farmàcia, Avinguda Vicent Andrés Estellés s/n, 46100 Burjassot, Spain.
Naunyn Schmiedebergs Arch Pharmacol. 2018 Apr;391(4):349-359. doi: 10.1007/s00210-018-1473-9. Epub 2018 Feb 6.
Atherosclerosis is one of the leading causes of death in Western countries, with high-density lipoproteins (HDL) playing an important protective role due to their ability to inhibit oxidation of low-density lipoproteins (LDL), thus relieving vascular subendothelial damage. One of the proteins constituting HDL particles is paraoxonase-1 (PON1), an enzyme able to hydrolyze aryl esters, lactones, and organophosphates. Other closely related paraoxonases are designated as PON2, which is a protein localized inside many different kinds of cells, and PON3, not only present in HDL but also in mitochondria and endoplasmic reticulum, as well. Given that the amount and the activity of PON1 in human serum are significantly lower in people suffering from cardiovascular diseases, enhancing both parameters might contribute to their treatment and prevention. One of the physiologically interesting substrates for the abovementioned hydrolytic cleavage is homocysteine thiolactone (HTL), an atherothrombotic active form of homocysteine. Although it was therefore postulated that PON1 would participate in preventing the HTL-mediated lipid peroxidation, some attention is recently paid to other enzymes, like biphenyl hydrolase-like protein, that seem to more selectively involved in lowering this risk factor. The aim of this paper is to elucidate the role of paraoxonases, especially PON1, by reviewing the latest studies in order to understand both its physiological role and modulation by drugs, nutrients, and plant extracts.
动脉粥样硬化是西方国家的主要死亡原因之一，高密度脂蛋白（HDL）因其能够抑制低密度脂蛋白（LDL）的氧化作用，从而减轻血管内皮下损伤，发挥着重要的保护作用。HDL 颗粒的组成蛋白之一是对氧磷酶-1（PON1），它是一种能够水解芳基酯、内酯和有机磷酸酯的酶。其他密切相关的对氧磷酶被指定为 PON2，它是一种定位于许多不同类型细胞内的蛋白质，而 PON3 不仅存在于 HDL 中，也存在于线粒体和内质网中。由于患有心血管疾病的人体内血清中 PON1 的数量和活性明显降低，因此提高这两个参数可能有助于治疗和预防心血管疾病。上述水解裂解的生理上有趣的底物之一是同型半胱氨酸硫内酯（HTL），它是同型半胱氨酸的一种动脉血栓形成活性形式。尽管因此推测 PON1 将参与预防 HTL 介导的脂质过氧化作用，但最近人们开始关注其他酶，如联苯水解酶样蛋白，这些酶似乎更选择性地参与降低这种风险因素。本文的目的是通过回顾最新的研究来阐明对氧磷酶，特别是 PON1 的作用，以了解其生理作用以及药物、营养物质和植物提取物对其的调节作用。
