Miyamoto Sayuri, Dupas Coralie, Murota Kaeko, Terao Junji
Department of Nutrition, School of Medicine, The University of Tokushima, Tokushima 770-8503, Japan.
Lipids. 2003 Jun;38(6):641-9. doi: 10.1007/s11745-003-1109-6.
The aim of this study was to determine the metabolic fate of phospholipid hydroperoxides (PLOOH) in rat gastric mucosa. Here we report evidence concerning the mechanism for PLOOH detoxification in gastric mucosa homogenate. Analysis by the TLC blot technique showed that the gastric mucosa has the highest potential to eliminate 1-palmitoyl-2-linoleoyl-phosphatidylcholine hydroperoxides (PL-PtdChoOOH) compared with the intestinal mucosa and liver. Major products detected after incubation with gastric mucosa were the partially reduced linoleic acid hydroperoxides (LAOOH) and lysophosphatidylcholine, indicating the involvement of phospholipase A2 (PLA2) in the elimination pathway. Using unilamellar vesicles, we demonstrated that gastric mucosal PLA2 does not distinguish between PLOOH and intact phospholipids. Although gastric mucosal PLA2 activity efficiently eliminated excess amounts of PLOOH, the complete reduction of LAOOH was dependent on the supply of exogenous GSH. In a separate experiment, administration of egg yolk PtdChoOOH to rats for 6 d significantly elevated GSH peroxidase (GPx) activity in the gastric mucosa. We concluded that excess amounts of PLOOH are efficiently eliminated through the hydrolysis by PLA2, and the subsequent reduction of FA hydroperoxide by GPx is the critical step for complete detoxification of oxidized phospholipids in the stomach.
本研究的目的是确定磷脂氢过氧化物（PLOOH）在大鼠胃黏膜中的代谢命运。在此，我们报告有关胃黏膜匀浆中PLOOH解毒机制的证据。通过薄层层析印迹技术分析表明，与肠黏膜和肝脏相比，胃黏膜消除1-棕榈酰-2-亚油酰磷脂酰胆碱氢过氧化物（PL-PtdChoOOH）的潜力最高。与胃黏膜孵育后检测到的主要产物是部分还原的亚油酸氢过氧化物（LAOOH）和溶血磷脂酰胆碱，表明磷脂酶A2（PLA2）参与了消除途径。使用单层囊泡，我们证明胃黏膜PLA2不能区分PLOOH和完整的磷脂。尽管胃黏膜PLA2活性有效地消除了过量的PLOOH，但LAOOH的完全还原依赖于外源性谷胱甘肽（GSH）的供应。在另一项实验中，给大鼠连续6天喂食蛋黄PtdChoOOH可显著提高胃黏膜中谷胱甘肽过氧化物酶（GPx）的活性。我们得出结论，过量的PLOOH通过PLA2水解被有效消除，随后GPx将脂肪酸氢过氧化物还原是胃中氧化磷脂完全解毒的关键步骤。
