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LPS-squalene interaction on d-galactose intestinal absorption

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Abstract

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.

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References

  1. Al-Sadi R, Guo S, Dokladny K, Smith MA, Ye D, Kaza A, Watterson DM, Ma TY (2012) Mechanism of interleukin-1beta induced-increase in mouse intestinal permeability in vivo. J Interf Cytokine Res 32:474–484. https://doi.org/10.1089/jir.2012.0031

    Article  CAS  Google Scholar 

  2. Al-Sadi R, Guo S, Ye D, Rawat M, Ma TY (2016) TNF-alpha modulation of intestinal tight junction permeability is mediated by NIK/IKK-alpha axis activation of the canonical NF-kappaB pathway. Am J Pathol 186:1151–1165. https://doi.org/10.1016/j.ajpath.2015.12.016

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Amador P, Garcia-Herrera J, Marca MC, de la Osada J, Acin S, Navarro MA, Salvador MT, Lostao MP, Rodriguez-Yoldi MJ (2007) Inhibitory effect of TNF-alpha on the intestinal absorption of galactose. J Cell Biochem 101:99–111. https://doi.org/10.1002/jcb.21168

    Article  CAS  PubMed  Google Scholar 

  4. Amador P, Garcia-Herrera J, Marca MC, de la Osada J, Acin S, Navarro MA, Salvador MT, Lostao MP, Rodriguez-Yoldi MJ (2007) Intestinal D-galactose transport in an endotoxemia model in the rabbit. J Membr Biol 215:125–133. https://doi.org/10.1007/s00232-007-9012-5

    Article  CAS  PubMed  Google Scholar 

  5. Amador P, Marca MC, Garcia-Herrera J, Lostao MP, Guillen N, de la Osada J, Rodriguez-Yoldi MJ (2008) Lipopolysaccharide induces inhibition of galactose intestinal transport in rabbits in vitro. Cell Physiol Biochem 22:715–724. https://doi.org/10.1159/000185555

    Article  CAS  PubMed  Google Scholar 

  6. Berkes J, Viswanathan VK, Savkovic SD, Hecht G (2003) Intestinal epithelial responses to enteric pathogens: effects on the tight junction barrier, ion transport, and inflammation. Gut 52:439–451

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Cardeno A, Magnusson MK, Strid H, Alarcon de La Lastra C, Sanchez-Hidalgo M, Ohman L (2014) The unsaponifiable fraction of extra virgin olive oil promotes apoptosis and attenuates activation and homing properties of T cells from patients with inflammatory bowel disease. Food Chem 161:353–360. https://doi.org/10.1016/j.foodchem.2014.04.016

    Article  CAS  PubMed  Google Scholar 

  8. Clayburgh DR, Rosen S, Witkowski ED, Wang F, Blair S, Dudek S, Garcia JG, Alverdy JC, Turner JR (2004) A differentiation-dependent splice variant of myosin light chain kinase, MLCK1, regulates epithelial tight junction permeability. J Biol Chem 279:55506–55513. https://doi.org/10.1074/jbc.M408822200

    Article  CAS  PubMed  Google Scholar 

  9. Chantret I, Rodolosse A, Barbat A, Dussaulx E, Brot-Laroche E, Zweibaum A, Rousset M (1994) Differential expression of sucrase-isomaltase in clones isolated from early and late passages of the cell line Caco-2: evidence for glucose-dependent negative regulation. J Cell Sci 107(Pt 1):213–225

    CAS  PubMed  Google Scholar 

  10. Choudhry N, Bajaj-Elliott M, McDonald V (2008) The terminal sialic acid of glycoconjugates on the surface of intestinal epithelial cells activates excystation of Cryptosporidium parvum. Infect Immun 76:3735–3741. https://doi.org/10.1128/IAI.00362-08

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Dawson DJ, Burrows PC, Lobley RW, Holmes R (1987) The kinetics of monosaccharide absorption by human jejunal biopsies: evidence for active and passive processes. Digestion 38:124–132. https://doi.org/10.1159/000199581

    Article  CAS  PubMed  Google Scholar 

  12. DeLuca S, Khar K, Meiler J (2015) Fully flexible docking of medium sized ligand libraries with RosettaLigand. PLoS One 10:e0132508. https://doi.org/10.1371/journal.pone.0132508

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Ferraris RP, Diamond J (1997) Regulation of intestinal sugar transport. Physiol Rev 77:257–302. https://doi.org/10.1152/physrev.1997.77.1.257

    Article  CAS  PubMed  Google Scholar 

  14. Garcia-Barrios A, Guillen N, Gascon S, Osada J, Vazquez CM, Miguel-Carrasco JL, Rodriguez-Yoldi MJ (2010) Nitric oxide involved in the IL-1beta-induced inhibition of fructose intestinal transport. J Cell Biochem 111:1321–1329. https://doi.org/10.1002/jcb.22859

    Article  CAS  PubMed  Google Scholar 

  15. Grosdidier A, Zoete V, Michielin O (2011) Fast docking using the CHARMM force field with EADock DSS. J Comput Chem 32:2149–2159. https://doi.org/10.1002/jcc.21797

    Article  CAS  PubMed  Google Scholar 

  16. Guo S, Al-Sadi R, Said HM, Ma TY (2012) Lipopolysaccharide causes an increase in intestinal tight junction permeability in vitro and in vivo by inducing enterocyte membrane expression and localization of TLR-4 and CD14. Am J Pathol 182:375–387. https://doi.org/10.1016/j.ajpath.2012.10.014

    Article  CAS  PubMed  Google Scholar 

  17. Hecht G, Koutsouris A (1999) Enteropathogenic E. coli attenuates secretagogue-induced net intestinal ion transport but not Cl- secretion. Am J Phys 276:G781–G788

    CAS  Google Scholar 

  18. Helliwell PA, Richardson M, Affleck J, Kellett GL (2000) Regulation of GLUT5, GLUT2 and intestinal brush-border fructose absorption by the extracellular signal-regulated kinase, p38 mitogen-activated kinase and phosphatidylinositol 3-kinase intracellular signalling pathways: implications for adaptation to diabetes. Biochem J 350(Pt 1):163–169

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Khoursandi S, Scharlau D, Herter P, Kuhnen C, Martin D, Kinne RK, Kipp H (2004) Different modes of sodium-D-glucose cotransporter-mediated D-glucose uptake regulation in Caco-2 cells. Am J Physiol Cell Physiol 287:C1041–C1047. https://doi.org/10.1152/ajpcell.00197.2004

    Article  CAS  PubMed  Google Scholar 

  20. Krimi RB, Letteron P, Chedid P, Nazaret C, Ducroc R, Marie JC (2009) Resistin-like molecule-beta inhibits SGLT-1 activity and enhances GLUT2-dependent jejunal glucose transport. Diabetes 58:2032–2038. https://doi.org/10.2337/db08-1786

    Article  PubMed  PubMed Central  Google Scholar 

  21. Lou-Bonafonte JM, Martinez-Beamonte R, Sanclemente T, Surra JC, Herrera-Marcos LV, Sanchez-Marco J, Arnal C, Osada J (2018) Current insights into the biological action of squalene. Mol Nutr Food Res 62:e1800136. https://doi.org/10.1002/mnfr.201800136

    Article  CAS  Google Scholar 

  22. Ma TY, Anderson JM (2012) Tight Junctions and the intestinal barrier. Inc: Physiology of the Gastrointestinal Tract. Elsevier Academic Press, Burlingtong, MA

    Google Scholar 

  23. Nighot M, Al-Sadi R, Guo S, Rawat M, Nighot P, Watterson MD, Ma TY (2017) Lipopolysaccharide-induced increase in intestinal epithelial tight permeability is mediated by toll-like receptor 4/myeloid differentiation primary response 88 (MyD88) activation of myosin light chain kinase expression. Am J Pathol 187:2698–2710. https://doi.org/10.1016/j.ajpath.2017.08.005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Pettersen EF, Goddard TD, Huang CC, Couch GS, Greenblatt DM, Meng EC, Ferrin TE (2004) UCSF chimera--a visualization system for exploratory research and analysis. J Comput Chem 25:1605–1612. https://doi.org/10.1002/jcc.20084

    Article  CAS  PubMed  Google Scholar 

  25. Reboredo-Rodriguez P, Varela-Lopez A, Forbes-Hernandez TY, Gasparrini M, Afrin S, Cianciosi D, Zhang J, Manna PP, Bompadre S, Quiles JL, Battino M, Giampieri F (2018) Phenolic compounds isolated from olive oil as nutraceutical tools for the prevention and management of cancer and cardiovascular diseases. Int J Mol Sci 19. https://doi.org/10.3390/ijms19082305

  26. Sanchez-Fidalgo S, Villegas I, Aparicio-Soto M, Cardeno A, Rosillo MA, Gonzalez-Benjumea A, Marset A, Lopez O, Maya I, Fernandez-Bolanos JG, Alarcon de la Lastra C (2015) Effects of dietary virgin olive oil polyphenols: hydroxytyrosyl acetate and 3, 4-dihydroxyphenylglycol on DSS-induced acute colitis in mice. J Nutr Biochem 26:513–520. https://doi.org/10.1016/j.jnutbio.2014.12.001

    Article  CAS  PubMed  Google Scholar 

  27. Sanchez-Fidalgo S, Villegas I, Rosillo MA, Aparicio-Soto M, de la Lastra CA (2014) Dietary squalene supplementation improves DSS-induced acute colitis by downregulating p38 MAPK and NFkB signaling pathways. Mol Nutr Food Res 59:284–292. https://doi.org/10.1002/mnfr.201400518

    Article  CAS  PubMed  Google Scholar 

  28. Shirazi-Beechey SP (1995) Molecular biology of intestinal glucose transport. Nutr Res Rev 8:27–41. https://doi.org/10.1079/NRR19950005

    Article  CAS  PubMed  Google Scholar 

  29. Simons KT, Kooperberg C, Huang E, Baker D (1997) Assembly of protein tertiary structures from fragments with similar local sequences using simulated annealing and Bayesian scoring functions. J Mol Biol 268:209–225. https://doi.org/10.1006/jmbi.1997.0959

    Article  CAS  PubMed  Google Scholar 

  30. Song Y, DiMaio F, Wang RY, Kim D, Miles C, Brunette T, Thompson J, Baker D (2013) High-resolution comparative modeling with RosettaCM. Structure 21:1735–1742. https://doi.org/10.1016/j.str.2013.08.005

    Article  CAS  PubMed  Google Scholar 

  31. Tsukita S, Furuse M, Itoh M (2001) Multifunctional strands in tight junctions. Nat Rev Mol Cell Biol 2:285–293. https://doi.org/10.1038/35067088

    Article  CAS  PubMed  Google Scholar 

  32. Turner JR (2009) Intestinal mucosal barrier function in health and disease. Nat Rev Immunol 9:799–809. https://doi.org/10.1038/nri2653

    Article  CAS  PubMed  Google Scholar 

  33. van Meerloo J, Kaspers GJ, Cloos J (2011) Cell sensitivity assays: the MTT assay. Methods Mol Biol 731:237–245. https://doi.org/10.1007/978-1-61779-080-5_20

    Article  CAS  PubMed  Google Scholar 

  34. Vayro S, Wood IS, Dyer J, Shirazi-Beechey SP (2001) Transcriptional regulation of the ovine intestinal Na+/glucose cotransporter SGLT1 gene. Role of HNF-1 in glucose activation of promoter function. Eur J Biochem 268:5460–5470

    Article  CAS  PubMed  Google Scholar 

  35. Veyhl M, Keller T, Gorboulev V, Vernaleken A, Koepsell H (2006) RS1 (RSC1A1) regulates the exocytotic pathway of Na+−D-glucose cotransporter SGLT1. Am J Physiol Renal Physiol 291:F1213–F1223. https://doi.org/10.1152/ajprenal.00068.2006

    Article  CAS  PubMed  Google Scholar 

  36. Vinuales C, Gascon S, Barranquero C, Osada J, Rodriguez-Yoldi MJ (2012) Inhibitory effect of IL-1beta on galactose intestinal absorption in rabbits. Cell Physiol Biochem 30:173–186. https://doi.org/10.1159/000339056

    Article  CAS  PubMed  Google Scholar 

  37. Vinuales C, Gascon S, Barranquero C, Osada J, Rodriguez-Yoldi MJ (2013) Interleukin-1beta reduces galactose transport in intestinal epithelial cells in a NF-kB and protein kinase C-dependent manner. Vet Immunol Immunopathol 155:171–181. https://doi.org/10.1016/j.vetimm.2013.06.016

    Article  CAS  PubMed  Google Scholar 

  38. Warleta F, Campos M, Allouche Y, Sanchez-Quesada C, Ruiz-Mora J, Beltran G, Gaforio JJ (2010) Squalene protects against oxidative DNA damage in MCF10A human mammary epithelial cells but not in MCF7 and MDA-MB-231 human breast cancer cells. Food Chem Toxicol 48:1092–1100. https://doi.org/10.1016/j.fct.2010.01.031

    Article  CAS  PubMed  Google Scholar 

  39. Watanabe A, Choe S, Chaptal V, Rosenberg JM, Wright EM, Grabe M, Abramson J (2010) The mechanism of sodium and substrate release from the binding pocket of vSGLT. Nature 468:988–991. https://doi.org/10.1038/nature09580

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Wiederstein M, Sippl MJ (2007) ProSA-web: interactive web service for the recognition of errors in three-dimensional structures of proteins. Nucleic Acids Res 35:W407–W410. https://doi.org/10.1093/nar/gkm290

    Article  PubMed  PubMed Central  Google Scholar 

  41. Xu J, Liu Z, Zhan W, Jiang R, Yang C, Zhan H, Xiong Y (2018) Recombinant TsP53 modulates intestinal epithelial barrier integrity via upregulation of ZO1 in LPSinduced septic mice. Mol Med Rep 17:1212–1218. https://doi.org/10.3892/mmr.2017.7946

    Article  CAS  PubMed  Google Scholar 

  42. Yu LC, Turner JR, Buret AG (2006) LPS/CD14 activation triggers SGLT-1-mediated glucose uptake and cell rescue in intestinal epithelial cells via early apoptotic signals upstream of caspase-3. Exp Cell Res 312:3276–3286. https://doi.org/10.1016/j.yexcr.2006.06.023

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

Molecular graphics and analyses were performed with the UCSF Chimera package. Chimera is developed by the Resource for Biocomputing, Visualization, and Informatics at the University of California, San Francisco (supported by NIGMS P41-GM103311).

Funding

This work was supported by grants from Grants from Ministerio de Economia y Competitividad, Gobierno de España (SAF2016-75441-R), CIBERobn (CB06/03/1012), Gobierno de Aragón (B16-R17), and SUDOE (Redvalue, SOE1/PI/E0123).

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Correspondence to Ma Jesús Rodríguez-Yoldi.

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Felices, M.J., Escusol, S., Martinez-Beamonte, R. et al. LPS-squalene interaction on d-galactose intestinal absorption. J Physiol Biochem 75, 329–340 (2019). https://doi.org/10.1007/s13105-019-00682-8

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