Department of Pharmacology and Physiology, University of Zaragoza, 50013, Zaragoza, Spain.
Department of Biochemistry, Molecular and Cellular Biology, Veterinary Faculty, University of Zaragoza, 50013, Zaragoza, Spain.
J Physiol Biochem. 2019 Aug;75(3):329-340. doi: 10.1007/s13105-019-00682-8. Epub 2019 May 3.
The dynamic and complex interactions between enteric pathogens and the intestinal epithelium often lead to disturbances in the intestinal barrier, altered fluid, electrolyte, and nutrient transport and can produce an inflammatory response. Lipopolysaccharide (LPS) is a complex polymer forming part of the outer membrane of Gram-negative bacteria. On the other hand, squalene is a triterpene present in high levels in the extra-virgin olive oil that has beneficial effects against several diseases and it has also anti-oxidant and anti-inflammatory properties. The aim of this work was to study whether the squalene could eliminate the LPS effect on D-galactose intestinal absorption in rabbits and Caco-2 cells. The results have shown that squalene reduced the effects of LPS on sugar absorption. High LPS doses increased D-galactose uptake through via paracellular but also decreased the active sugar transport because the SGLT1 levels were diminished. However, the endotoxin effect on the paracellular way seemed to be more important than on the transcellular route. At the same time, an increased in RELM-β expression was observed. This event could be related to inflammation and cause a decrease in SGLT1 levels. In addition, MLCK protein is also increased by LPS which could lead to an increase in sugar transport through tight junctions. At low doses, the LPS could inhibit SGLT1 intrinsic activity. Bioinformatic studies by docking confirm the interaction between LPS-squalene as well as occur through MLCK and SGLT-1 proteins.
肠病原体与肠道上皮之间的动态和复杂相互作用通常会导致肠道屏障紊乱、改变液体、电解质和营养物质的转运，并产生炎症反应。脂多糖 (LPS) 是一种形成革兰氏阴性菌外膜一部分的复杂聚合物。另一方面，角鲨烯是一种在特级初榨橄榄油中含量很高的三萜烯，对多种疾病具有有益的作用，它还具有抗氧化和抗炎特性。这项工作的目的是研究角鲨烯是否可以消除 LPS 对兔和 Caco-2 细胞中 D-半乳糖肠吸收的影响。结果表明，角鲨烯降低了 LPS 对糖吸收的影响。高 LPS 剂量通过细胞旁途径增加 D-半乳糖摄取，但也降低了主动糖转运，因为 SGLT1 水平降低。然而，内毒素对细胞旁途径的影响似乎比细胞内途径更为重要。同时，观察到 RELM-β 的表达增加。这一事件可能与炎症有关，并导致 SGLT1 水平降低。此外，LPS 还会增加 MLCK 蛋白，这可能导致通过紧密连接增加糖转运。在低剂量下，LPS 可以抑制 SGLT1 的固有活性。通过对接进行的生物信息学研究证实了 LPS-角鲨烯的相互作用，以及通过 MLCK 和 SGLT-1 蛋白的相互作用。
