Rao Manjunath N, Marmillot Philippe, Gong Maoka, Palmer David A, Seeff Leonard B, Strader Doris B, Lakshman M Raj
Lipid Research Laboratory and Gastrointestinal and Hepatology Section, Veterans Affairs Medical Center, Washington DC 20422, USA.
Metabolism. 2003 Oct;52(10):1287-94. doi: 10.1016/s0026-0495(03)00191-4.
Paraoxonase 1 (PON) may contribute to the cardioprotective action of high-density lipoprotein (HDL) because it inhibits low-density lipoprotein (LDL) oxidation, a prerequisite for the onset of atherosclerosis. Because light drinking and heavy drinking have diametrically opposite effects on cardioprotection, we have determined the effects of ethanol dosage on rat serum PON activity and its hepatic expression. Furthermore, we have investigated PON activity and polymorphism in human light and heavy drinkers. Our results confirm that HDL-PON inhibited LDL oxidation, destroyed oxidized LDL, and inhibited its uptake by macrophages. Light ethanol feeding caused a 20% to 25% (P <.05) increase in PON activity in both serum and liver and a 59% (P <.001) increase in the level of liver PON mRNA compared with pair-fed control rats. In contrast, heavy ethanol feeding caused a 25% (P <.05) decrease in serum and liver PON activities with a 51% (P <.01) decrease in liver PON mRNA level. Light drinkers had a 395% (P <.001) higher, whereas heavy drinkers had a 45% (P <.001) lower serum PON activity compared with nondrinkers. Significantly, the number of homozygotes versus heterozygotes with respect to high or low activity PON phenotype was similar in all the groups. Therefore, we conclude that light drinking upregulates, whereas heavy drinking downregulates PON activity and its expression, irrespective of its genetic polymorphism.
对氧磷酶1（PON）可能有助于高密度脂蛋白（HDL）的心脏保护作用，因为它能抑制低密度脂蛋白（LDL）氧化，而LDL氧化是动脉粥样硬化发生的一个前提条件。由于少量饮酒和大量饮酒对心脏保护有截然相反的作用，我们已经确定了乙醇剂量对大鼠血清PON活性及其肝脏表达的影响。此外，我们还研究了少量饮酒者和大量饮酒者的PON活性及基因多态性。我们的结果证实，HDL-PON抑制LDL氧化，破坏氧化型LDL，并抑制巨噬细胞对其摄取。与配对喂食的对照大鼠相比，少量喂食乙醇导致血清和肝脏中的PON活性增加20%至25%（P<.05），肝脏PON mRNA水平增加59%（P<.001）。相反，大量喂食乙醇导致血清和肝脏中的PON活性降低25%（P<.05），肝脏PON mRNA水平降低51%（P<.01）。与不饮酒者相比，少量饮酒者的血清PON活性高395%（P<.001），而大量饮酒者的血清PON活性低45%（P<.001）。值得注意的是，在所有组中，高活性或低活性PON表型的纯合子与杂合子数量相似。因此，我们得出结论，少量饮酒会上调PON活性及其表达，而大量饮酒则会下调PON活性及其表达，与基因多态性无关。
