Hepatocyte-secreted extracellular vesicles modify blood metabolome and endothelial function by an arginase-dependent mechanism

Scientific Reports

Volumn 7, Issue , 2017, Pages

  Royo, Felix ^a   Moreno, Laura ^b   Mleczko, Justyna ^a   Palomo, Laura ^a   Gonzalez, Esperanza ^a   Cabrera, Diana ^a   Cogolludo, Angel ^b   Vizcaino, Francisco Perez ^b   Van Liempd, Sebastiaan ^a   Falcon Perez, Juan M ^a,c  

^a INSTITUTO DE SALUD CARLOS III   (Spain)

^b UNIVERSIDAD COMPLUTENSE DE MADRID   (Spain)

^c BASQUE FOUNDATION FOR SCIENCE   (Spain)

Author keywords

[No Author keywords available]

Indexed keywords

ACETYLCHOLINE; ARGINASE; CD63 ANTIGEN; CD63 PROTEIN, RAT; CD81 ANTIGEN; CD81 PROTEIN, RAT;

ANIMAL; BLOOD; CELL CULTURE; CYTOLOGY; DRUG EFFECT; ENZYMOLOGY; EXOSOME; LIVER CELL; MALE; METABOLISM; METABOLOMICS; PHYSIOLOGY; PROCEDURES; RAT; SECRETION (PROCESS); VASCULAR ENDOTHELIUM;

ACETYLCHOLINE; ANIMALS; ARGINASE; BLOOD; CELLS, CULTURED; ENDOTHELIUM, VASCULAR; EXTRACELLULAR VESICLES; HEPATOCYTES; MALE; METABOLOMICS; RATS; TETRASPANIN 28; TETRASPANIN 30;

EID: 85013191719     PISSN: None     EISSN: 20452322     Source Type: Journal    
DOI: 10.1038/srep42798     Document Type: Article

References (56)

1. Conde-Vancells, J., et al. Characterization and comprehensive proteome profiling of exosomes secreted by hepatocytes. Journal of proteome research 7, 5157-5166 (2008).
2. Gonzalez, E., Falcon-Perez, J. M. Cell-derived extracellular vesicles as a platform to identify low-invasive disease biomarkers. Expert review of molecular diagnostics 15, 907-923, doi: 10.1586/14737159.2015.1043272 (2015).
3. Herrera, M. B., et al. Human liver stem cells improve liver injury in a model of fulminant liver failure. Hepatology 57, 311-319, doi: 10.1002/hep.25986 (2013).
4. Herrera, M. B., et al. Human liver stem cell-derived microvesicles accelerate hepatic regeneration in hepatectomized rats. Journal of cellular and molecular medicine 14, 1605-1618, doi: 10.1111/j.1582-4934.2009.00860.x (2010).
5. Herrera Sanchez, M. B., et al. Human liver stem cells and derived extracellular vesicles improve recovery in a murine model of acute kidney injury. Stem cell research & therapy 5, 124, doi: 10.1186/scrt514 (2014).
6. Nojima, H., et al. Hepatocyte exosomes mediate liver repair and regeneration via sphingosine-1-phosphate. Journal of hepatology, doi: 10.1016/j.jhep.2015.07.030 (2015).
7. Hirsova, P., et al. Lipid-Induced Signaling Causes Release of Inflammatory Extracellular Vesicles From Hepatocytes. Gastroenterology 150, 956-967, doi: 10.1053/j.gastro.2015.12.037 (2016).
8. Conde-Vancells, J., Gonzalez, E., Lu, S. C., Mato, J. M., Falcon-Perez, J. M. Overview of extracellular microvesicles in drug metabolism. Expert opinion on drug metabolism & toxicology 6, 543-554, doi: 10.1517/17425251003614766 (2010).
9. Holman, N. S., Mosedale, M., Wolf, K. K., LeCluyse, E. L., Watkins, P. B. Sub-toxic alterations in hepatocyte-derived exosomes: an early step in drug-induced liver injury Toxicological sciences: an official journal of the Society of Toxicology, doi: 10.1093/toxsci/kfw047 (2016).
10. Yanez-Mo, M., et al. Biological properties of extracellular vesicles and their physiological functions. Journal of extracellular vesicles 4, 27066, doi: 10.3402/jev.v4.27066 (2015).
11. Rodriguez-Suarez, E., et al. Quantitative proteomic analysis of hepatocyte-secreted extracellular vesicles reveals candidate markers for liver toxicity. Journal of proteomics 103, 227-240, doi: 10.1016/j.jprot.2014.04.008 (2014).
12. Gonzalez, E., et al. Serum UPLC-MS/MS metabolic profiling in an experimental model for acute-liver injury reveals potential biomarkers for hepatotoxicity. Metabolomics: Official journal of the Metabolomic Society 8, 997-1011, doi: 10.1007/s11306-011-0329-9 (2012).
13. Weckwerth, W. Metabolomics: an integral technique in systems biology. Bioanalysis 2, 829-836, doi: 10.4155/bio.09.192 (2010).
14. Royo, F., et al. Metabolically active extracellular vesicles released from hepatocytes under drug-induced liver-damaging conditions modify serum metabolome and might affect different pathophysiological processes. European journal of pharmaceutical sciences: official journal of the European Federation for Pharmaceutical Sciences, doi: 10.1016/j.ejps.2016.10.020 (2016).
15. Caldwell, R. B., Toque, H. A., Narayanan, S. P., Caldwell, R. W. Arginase: an old enzyme with new tricks. Trends Pharmacol Sci 36, 395-405, doi: 10.1016/j.tips.2015.03.006 (2015).
16. Durante, W., Johnson, F. K., Johnson, R. A. Arginase: a critical regulator of nitric oxide synthesis and vascular function. Clinical and experimental pharmacology & physiology 34, 906-911, doi: 10.1111/j.1440-1681.2007.04638.x (2007).
17. Boucher, J. L., Moali, C., Tenu, J. P. Nitric oxide biosynthesis, nitric oxide synthase inhibitors and arginase competition for L-arginine utilization. Cell Mol Life Sci 55, 1015-1028 (1999).
18. Pernow, J., Kiss, A., Tratsiakovich, Y., Climent, B. Tissue-specific up-regulation of arginase I and II induced by p38 MAPK mediates endothelial dysfunction in type 1 diabetes mellitus. British journal of pharmacology 172, 4684-4698, doi: 10.1111/bph.13242 (2015).
19. Johnstone, R. M., Adam, M., Hammond, J. R., Orr, L., Turbide, C. Vesicle formation during reticulocyte maturation. Association of plasma membrane activities with released vesicles (exosomes). The Journal of biological chemistry 262, 9412-9420 (1987).
20. Clayton, A., Al-Taei, S., Webber, J., Mason, M. D., Tabi, Z. Cancer exosomes express CD39 and CD73, which suppress T cells through adenosine production. Journal of immunology 187, 676-683, doi: 10.4049/jimmunol.1003884 (2011).
21. Royo, F., et al. Transcriptome of extracellular vesicles released by hepatocytes. PloS one 8, e68693, doi: 10.1371/journal.pone.0068693 (2013).
22. Lotvall, J., et al. Minimal experimental requirements for definition of extracellular vesicles and their functions: a position statement from the International Society for Extracellular Vesicles. J Extracell Vesicles 3, 26913, doi: 10.3402/jev.v3.26913 (2014).
23. Shin, C. Y., et al. Adenosine and purine nucleosides protect rat primary astrocytes from peroxynitrite-potentiated, glucose deprivation-induced death: preservation of intracellular ATP level. Exp Neurol 176, 175-182 (2002).
24. Szoleczky, P., et al. Identification of agents that reduce renal hypoxia-reoxygenation injury using cell-based screening: purine nucleosides are alternative energy sources in LLC-PK1 cells during hypoxia. Arch Biochem Biophys 517, 53-70, doi: 10.1016/j. abb.2011.11.005 (2012).
25. Balestri, F., et al. Purine and pyrimidine nucleosides preserve human astrocytoma cell adenylate energy charge under ischemic conditions. Neurochem Int 50, 517-523, doi: 10.1016/j.neuint.2006.10.005 (2007).
26. Salleron, L., et al. DERA is the human deoxyribose phosphate aldolase and is involved in stress response. Biochim Biophys Acta 1843, 2913-2925, doi: 10.1016/j.bbamcr.2014.09.007 (2014).
27. Yanai, N., Shiotani, S., Hagiwara, S., Nabetani, H., Nakajima, M. Antioxidant combination inhibits reactive oxygen species mediated damage. Biosci Biotechnol Biochem 72, 3100-3106, doi: 10.1271/bbb.80159 (2008).
28. Hanigan, M. H. Gamma-glutamyl transpeptidase: redox regulation and drug resistance. Adv Cancer Res 122, 103-141, doi: 10.1016/B978-0-12-420117-0.00003-7 (2014).
29. Bielli, A., Scioli, M. G., Mazzaglia, D., Doldo, E., Orlandi, A. Antioxidants and vascular health. Life Sci 143, 209-216, doi: 10.1016/j. lfs.2015.11.012 (2015).
30. Jiang, M., et al. Arginase-flotillin interaction brings arginase to red blood cell membrane. FEBS letters 580, 6561-6564, doi: 10.1016/j. febslet.2006.11.003 (2006).
31. Bailey, W. J., et al. A performance evaluation of three drug-induced liver injury biomarkers in the rat: alpha-glutathione S-transferase, arginase 1, and 4-hydroxyphenyl-pyruvate dioxygenase. Toxicological sciences: an official journal of the Society of Toxicology 130, 229-244, doi: 10.1093/toxsci/kfs243 (2012).
32. Ozcelik, E., Uslu, S., Burukoglu, D., Musmul, A. Chitosan and blueberry treatment induces arginase activity and inhibits nitric oxide production during acetaminophen-induced hepatotoxicity. Pharmacognosy magazine 10, S217-224, doi: 10.4103/0973-1296.133234 (2014).
33. Brodsky, S. V., et al. Dynamics of circulating microparticles in liver transplant patients. Journal of gastrointestinal and liver diseases: JGLD 17, 261-268 (2008).
34. Jeyabalan, G., et al. Arginase blockade protects against hepatic damage in warm ischemia-reperfusion. Nitric oxide: biology and chemistry/official journal of the Nitric Oxide Society 19, 29-35, doi: 10.1016/j.niox.2008.04.002 (2008).
35. Matuschak, G. M. Liver-lung interactions in critical illness. New Horiz 2, 488-504 (1994).
36. Rodriguez-Roisin, R., Krowka, M. J., Herve, P., Fallon, M. B., Committee, E. R. S. T. F. P.-H. V. D. S. Pulmonary-Hepatic vascular Disorders (PHD). Eur Respir J 24, 861-880, doi: 10.1183/09031936.04.00010904 (2004).
37. Baudouin, S. V., Howdle, P., O'Grady, J. G., Webster, N. R. Acute lung injury in fulminant hepatic failure following paracetamol poisoning. Thorax 50, 399-402 (1995).
38. Rautou, P. E., et al. Abnormal plasma microparticles impair vasoconstrictor responses in patients with cirrhosis. Gastroenterology 143, 166-176 e166, doi: 10.1053/j.gastro.2012.03.040 (2012).
39. Amabile, N., et al. Cellular microparticles in the pathogenesis of pulmonary hypertension. Eur Respir J 42, 272-279, doi: 10.1183/09031936.00087212 (2013).
40. Tual-Chalot, S., et al. Circulating microparticles from pulmonary hypertensive rats induce endothelial dysfunction. Am J Respir Crit Care Med 182, 261-268, doi: 10.1164/rccm.200909-1347OC (2010).
41. McVey, M., Tabuchi, A., Kuebler, W. M. Microparticles and acute lung injury. Am J Physiol Lung Cell Mol Physiol 303, L364-381, doi: 10.1152/ajplung.00354.2011 (2012).
42. Klinger, J. R., Abman, S. H., Gladwin, M. T. Nitric oxide deficiency and endothelial dysfunction in pulmonary arterial hypertension. Am J Respir Crit Care Med 188, 639-646, doi: 10.1164/rccm.201304-0686PP (2013).
43. Shemyakin, A., et al. Arginase inhibition improves endothelial function in patients with coronary artery disease and type 2 diabetes mellitus. Circulation 126, 2943-2950, doi: 10.1161/CIRCULATIONAHA.112.140335 (2012).
44. Tsikas, D., Boger, R. H., Sandmann, J., Bode-Boger, S. M., Frolich, J. C. Endogenous nitric oxide synthase inhibitors are responsible for the L-arginine paradox. FEBS Lett 478, 1-3 (2000).
45. Aliotta, J. M., et al. Exosomes induce and reverse monocrotaline-induced pulmonary hypertension in mice. Cardiovasc Res 110, 319-330, doi: 10.1093/cvr/cvw054 (2016).
46. Saitoh, W., Yamauchi, S., Watanabe, K., Takasaki, W., Mori, K. Metabolomic analysis of arginine metabolism in acute hepatic injury in rats. J Toxicol Sci 39, 41-50 (2014).
47. Sasaki, A., Doi, S., Mizutani, S., Azuma, H. Roles of accumulated endogenous nitric oxide synthase inhibitors, enhanced arginase activity, and attenuated nitric oxide synthase activity in endothelial cells for pulmonary hypertension in rats. Am J Physiol Lung Cell Mol Physiol 292, L1480-1487, doi: 10.1152/ajplung.00360.2006 (2007).
48. Nara, A., et al. Pulmonary arterial hypertension in rats due to age-related arginase activation in intermittent hypoxia. Am J Respir Cell Mol Biol 53, 184-192, doi: 10.1165/rcmb.2014-0163OC (2015).
49. Stenmark, K. R., Tuder, R. M., El Kasmi, K. C. Metabolic reprogramming and inflammation act in concert to control vascular remodeling in hypoxic pulmonary hypertension. J Appl Physiol (1985) 119, 1164-1172, doi: 10.1152/japplphysiol.00283.2015 (2015).
50. Grasemann, H., et al. Arginase inhibition prevents bleomycin-induced pulmonary hypertension, vascular remodeling, and collagen deposition in neonatal rat lungs. Am J Physiol Lung Cell Mol Physiol 308, L503-510, doi: 10.1152/ajplung.00328.2014 (2015).
51. Hsu, L. L., et al. Hemolysis in sickle cell mice causes pulmonary hypertension due to global impairment in nitric oxide bioavailability. Blood 109, 3088-3098, doi: 10.1182/blood-2006-08-039438 (2007).
52. Kao, C. C., et al. Arginine metabolic endotypes in pulmonary arterial hypertension. Pulm Circ 5, 124-134, doi: 10.1086/679720 (2015).
53. Morris, C. R., et al. Dysregulated arginine metabolism, hemolysis-associated pulmonary hypertension, and mortality in sickle cell disease. JAMA 294, 81-90, doi: 10.1001/jama.294.1.81 (2005).
54. Thery, C., Amigorena, S., Raposo, G., Clayton, A. Isolation and characterization of exosomes from cell culture supernatants and biological fluids. Current protocols in cell biology/editorial board, Juan S. Bonifacino ... [et al.] Chapter 3, Unit 3 22, doi: 10.1002/0471143030.cb0322s30 (2006).
55. Raposo, G., et al. B lymphocytes secrete antigen-presenting vesicles. J Exp Med 183, 1161-1172 (1996).
56. Moral-Sanz, J., et al. Different patterns of pulmonary vascular disease induced by type 1 diabetes and moderate hypoxia in rats. Experimental physiology 97, 676-686, doi: 10.1113/expphysiol.2011.062257 (2012).