Dept. of Environmental and Occupational Health Sciences, University of Washington, 4225 Roosevelt Way NE, Seattle, WA 98105, USA.
Biochem Pharmacol. 2011 Feb 1;81(3):337-44. doi: 10.1016/j.bcp.2010.11.008. Epub 2010 Nov 18.
Paraoxonase 1 (PON1) is a high density lipoprotein (HDL)-associated enzyme displaying esterase and lactonase activity. PON1 hydrolyzes several organophosphorus (OP) insecticides and nerve agents, a number of exogenous and endogenous lactones, and metabolizes toxic oxidized lipids of low density lipoproteins (LDL) and HDL. As such, PON1 plays a relevant role in determining susceptibility to OP toxicity, cardiovascular diseases and several other diseases. Serum PON1 activity in a given population can vary by at least 40-fold. Most of this variation can be accounted for by genetic polymorphisms in the coding region (Q192R, L55M) and in the promoter region (T-108C). However, exogenous factors may also modulate PON1 activity and/or level of expression. This paper examines various factors that have been found to positively modulate PON1. Certain drugs (e.g. hypolipemic and anti-diabetic compounds), dietary factors (antioxidants, polyphenols), and life-style factors (moderate alcohol consumption) appear to increase PON1 activity. Given the relevance of PON1 in protecting from certain environmental exposure and from cardiovascular and other diseases, there is a need for further mechanistic, animal, and clinical research in this area, and for consideration of possible alternative strategies for increasing the levels and activity of PON1.
对氧磷酶 1（PON1）是一种高密度脂蛋白（HDL）相关的酶，具有酯酶和内酯酶活性。PON1 可以水解多种有机磷（OP）杀虫剂和神经毒剂、许多外源性和内源性内酯，以及代谢 LDL 和 HDL 中有毒的氧化脂质。因此，PON1 在确定对 OP 毒性、心血管疾病和其他几种疾病的易感性方面发挥着重要作用。在给定人群中，血清 PON1 活性的差异至少可达 40 倍。这种差异的大部分可以用编码区（Q192R、L55M）和启动子区（T-108C）的遗传多态性来解释。然而，外源性因素也可能调节 PON1 的活性和/或表达水平。本文研究了已发现可正向调节 PON1 的各种因素。某些药物（如降脂和抗糖尿病化合物）、饮食因素（抗氧化剂、多酚）和生活方式因素（适度饮酒）似乎可以增加 PON1 的活性。鉴于 PON1 在保护人体免受某些环境暴露和心血管疾病及其他疾病方面的重要性，需要在这一领域进行进一步的机制、动物和临床研究，并考虑提高 PON1 水平和活性的可能替代策略。
