Abstract
Embryonic survival requires histotrophic nutrition, including molecules secreted or transported into the uterine lumen by uterine epithelia. l-Arginine (Arg) is a common substrate for synthesis of nitric oxide, ornithine, proline, glutamate, creatinine, urea, polyamines and agmatine. Agmatine (Agm) is a product of arginine decarboxylation and it is a substrate for agmatinase for synthesis of putrescine and other polyamines in the ovine conceptus. Polyamines are essential for conceptus development. Therefore, this study compared effects of Arg and Agm on the behavior of ovine trophectoderm (oTr1) cells cultured in vitro. Arg, but not Agm, increased proliferation and migration of oTr1 cells, but neither Arg nor Agm affected cell adhesion. The total amount of IFNT in culture medium of oTr1 cells was increased by Arg, but Agm increased the IFNT production per oTr1 cell. Arg and Agm plus Arg decreased secretion of dopamine and norepinephrine by oTr1 cells. Agm upregulates expression of mRNAs SLC7A1, agmatinase and OAZ2 while the combination of Arg and Agm decreased expression of mRNAs for ODC1, SLC7A1, OAZ1 and OAZ3 by oTr1 cells. Although Agm does not stimulate proliferation, migration or adhesion of oTr1 cells or their secretion of catecholamines, Agm did increase transcription of SLC7A1, agmatinase and OAZ2 genes which would increase the capacity of oTr1 cells to produce polyamines. Collectively, our findings suggest a role for Arg and Agm in the regulation of transport of basic amino acids (including Arg), polyamine synthesis, and secretion of catecholamines by oTr1 cells.
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Abbreviations
- ADC:
-
Arginine decarboxylase
- AGMAT:
-
Agmatinase
- Arg:
-
l-Arginine
- Agm:
-
Agmatine
- OAZ:
-
Antienzyme
- CM:
-
Complete medium
- FBS:
-
Fetal bovine serum
- IFNT:
-
Interferon tau
- NO:
-
Nitric oxide
- ODC1:
-
Ornithine decarboxylase
- oTr1:
-
Ovine trophectoderm primary cell line
References
Bazer FW, Spencer TE, Ott TL (1997) Interferon tau: a novel pregnancy recognition signal. Am J Reprod Immunol 37:412–420
Bazer FW, Spencer TE, Johnson GA et al (2009) Comparative aspects of implantation. Reproduction 138:195–209
Bazer FW, Spencer TE, Johnson GA et al (2010a) Uterine receptivity to implantation of blastocysts in mammals. Front Biosci (Schol Ed) 3:745–767
Bazer FW, Wu G, Spencer TE et al (2010b) Novel pathways for implantation and establishment and maintenance of pregnancy in mammals. Mol Hum Reprod 16:135–152
Bazer FW, Song G, Kim J et al (2012) Mechanistic mammalian target of rapamycin (MTOR) cell signaling: effects of select nutrients and secreted phosphoprotein 1 on development of mammalian conceptuses. Mol Cell Endocrinol 354:22–33
Bazer FW, Johnson GA, Wu G (2015a) Amino acids and conceptus development during the peri-implantation period of pregnancy. Adv Exp Med Biol 843:23–52
Bazer FW, Ying W, Wang XQ et al (2015b) The many faces of interferon tau. Amino Acids 47:449–460
Coffino P (2001) Regulation of cellular polyamines by antizyme. Nat Rev Mol Cell Biol 2:188–194
Dudkowska M, Lai J, Gardini G et al (2003) Agmatine modulates the in vivo biosynthesis and interconversion of polyamines and cell proliferation. Biochim Biophys Acta 1619:159–166
Farmer JL, Burghardt RC, Jousan FD et al (2008) Galectin 15 (LGALS15) functions in trophectoderm migration and attachment. FASEB J 22:548–560
Gao H, Wu G, Spencer TE et al (2009a) Select nutrients in the ovine uterine lumen. I. Amino acids, glucose, and ions in uterine luminal flushings of cyclic and pregnant ewes. Biol Reprod 80:86–93
Gao H, Wu G, Spencer TE et al (2009b) Select nutrients in the ovine uterine lumen. III. Cationic amino acid transporters in the ovine uterus and peri-implantation conceptuses. Biol Reprod 80:602–609
Gardini G, Cravanzola C, Autelli R et al (2003) Agmatine inhibits the proliferation of rat hepatoma cells by modulation of polyamine metabolism. J Hepatol 39:793–799
Gründemann D, Hahne C, Berkels R et al (2003) Agmatine is efficiently transported by non-neuronal monoamine transporters extraneuronal monoamine transporter (EMT) and organic cation transporter 2 (OCT2). J Pharmacol Exp Ther 304:810–817
Isome M, Lortie MJ, Murakami Y et al (2007) The antiproliferative effects of agmatine correlate with the rate of cellular proliferation. Am J Physiol Cell Physiol 293:705–711
Kim J, Song G, Gao H et al (2008) Insulin-like growth factor II activates phosphatidylinositol 3-kinase-protooncogenic protein kinase 1 and mitogen-activated protein kinase cell signaling pathways, and stimulates migration of ovine trophectoderm cells. Endocrinology 149:3085–3094
Kim JY, Burghardt RC, Wu G et al (2011a) Select nutrients in the ovine uterine lumen. VII. Effects of arginine, leucine, glutamine, and glucose on trophectoderm cell signaling, proliferation, and migration. Biol Reprod 84:62–69
Kim JY, Burghardt RC, Wu G et al (2011b) Select nutrients in the ovine uterine lumen. VII. Effects of arginine, leucine, glutamine, and glucose on trophectoderm cell signaling, proliferation, and migration. Biol Reprod 84:62–69
Kwon H, Spencer TE, Bazer FW et al (2003a) Developmental changes of amino acids in ovine fetal fluids. Biol Reprod 68:1813–1820
Kwon H, Wu G, Bazer FW et al (2003b) Developmental changes in polyamine levels and synthesis in the ovine conceptus. Biol Reprod 69:1626–1634
Lee HY, Mohammed KA, Goldberg EP et al (2013) Arginine-conjugated albumin microspheres inhibits proliferation and migration in lung cancer cells. Am J Cancer Res 3:266–277
Li G, Regunathan S, Barrow CJ et al (1994) Agmatine: an endogenous clonidine-displacing substance in the brain. Science 263:966–969
Li G, Regunathan S, Reis DJ (1995) Agmatine is synthesized by a mitochondrial arginine decarboxylase in rat brain. Ann N Y Acad Sci 763:325–329
López C, Ramos MB, Cremades A et al (2010) Antizyme inhibitor 2: molecular, cellular and physiological aspects. Amino Acids 38:603–611
Mangold U (2005) The antizyme family: polyamines and beyond. IUBMB Life 57:671–676
Mateo RD, Wu G, Bazer FW et al (2007) Dietary l-arginine supplementation enhances the reproductive performance of gilts. J Nutr 137:652–656
Mistry SK, Burwell TJ, Chambers RM et al (2002) Cloning of human agmatinase. An alternate path for polyamine synthesis induced in liver by hepatitis B virus. Am J Physiol Gastrointest Liver Physiol 282:375–381
Molderings G, Bönisch H, Göthert M et al (2001) Agmatine and putrescine uptake in the human glioma cell line SK-MG-1. Naunyn Schmiedebergs Arch Pharmacol 363:671–679
Palomba L, Persichini T, Mazzone V et al (2004) Inhibition of nitric-oxide synthase-I (NOS-I)-dependent nitric oxide production by lipopolysaccharide plus interferon-γ is mediated by arachidonic acid. Effects on NFΚB activation and late inducible NOS expression. J Biol Chem 279:29895–29901
Piletz JE, Aricioglu F, Cheng JT et al (2013) Agmatine: clinical applications after 100 years in translation. Drug Discov Today 18:880–893
Raspotnig G, Fauler G, Jantscher A et al (1999) Colorimetric determination of cell numbers by Janus green staining. Anal Biochem 275:74–83
Regunathan S, Piletz J (2003) Regulation of inducible nitric oxide synthase and agmatine synthesis in macrophages and astrocytes. Ann N Y Acad Sci 1009:20–29
Reis DJ, Regunathan S (1999) Agmatine: an endogenous ligand at imidazoline receptors is a novel neurotransmitter. Ann N Y Acad Sci 881:65–80
Renzo GC, Clerici G, Neri I et al (2005) Potential effects of nutrients on placental function and fetal growth. Nestle Nutr Workshop Ser Pediatr Program 55:73–78
Rezaei R, Knabe DA, Tekwe CD et al (2013) Dietary supplementation with monosodium glutamate is safe and improves growth performance in postweaning pigs. Amino Acids 44:911–923
Sala RM, Li DC, Dake GR et al (2013) Polyamine transport by the polyspecific organic cation transporters OCT1, OCT2, and OCT3. Mol Pharmacol 10:1450–1458
Satriano J, Matsufuji S, Murakami Y et al (1998) Agmatine suppresses proliferation by frameshift induction of antizyme and attenuation of cellular polyamine levels. J Biol Chem 273:15313–15316
Satriano J, Isome M, Casero RA (2001) Polyamine transport system mediates agmatine transport in mammalian cells. Am J Physiol Cell Physiol 281:329–334
Tabor CW, Tabor H (1984) Polyamines. Ann Rev Biochem 53:749–790
Tapella L, Stravalaci M, Bastone A et al (2013) Epitope scanning indicates structural differences in brain-derived monomeric and aggregated mutant prion proteins related to genetic prion diseases. Biochem J 454:417–425
Tian H, Hammer RE, Matsumoto AM et al (1998) The hypoxia-responsive transcription factor EPAS1 is essential for catecholamine homeostasis and protection against heart failure during embryonic development. Genes Dev 12:3320–3324
Toninello A, Battaglia V, Salvi M et al (2006) Structural characterization of agmatine at physiological conditions. Struct Chem 17:163–175
Wang JF, Su RB, Wu N et al (2005) Inhibitory effect of agmatine on proliferation of tumor cells by modulation of polyamine metabolism. Acta Pharmacol Sin 26:616–622
Wang X, Wei Y, Dunlap KA et al (2014) Arginine decarboxylase and agmatinase: an alternative pathway for de novo biosynthesis of polyamines for development of mammalian conceptuses. Biol Reprod 90:84
Wang X, Burghardt RC, Romero JJ et al (2015) Functional roles of arginine during the peri-implantation period of pregnancy. III. Arginine stimulates proliferation and interferon tau production by ovine trophectoderm cells via nitric oxide and polyamine-TSC2-MTOR signaling pathways. Biol Reprod 92:75
Wolf C, Bruess M, Haenisch B et al (2007) Molecular basis for the antiproliferative effect of agmatine in tumor cells of colonic, hepatic, and neuronal origin. Mol Pharmacol 71:276–283
Wu G (2009) Amino acids: metabolism, functions, and nutrition. Amino Acids 37:1–17
Wu G, Flynn NE, Knabe DA (2000) Enhanced intestinal synthesis of polyamines from proline in cortisol-treated piglets. Am J Physiol Endocrinol Metab 279:395–402
Wu N, Xu B, Liu Y et al (2005) Inhibitory effect of agmatine on proliferation of tumor cells by modulation of polyamine metabolism. Acta Pharmacol Sin 26:616–622
Wu G, Bazer FW, Davis TA et al (2009) Arginine metabolism and nutrition in growth, health and disease. Amino Acids 37:153–168
Wu G, Bazer FW, Satterfield MC et al (2013) Impacts of arginine nutrition on embryonic and fetal development in mammals. Amino Acids 45:241–256
Xiao XM, Li LP (2005) l-Arginine treatment for asymmetric fetal growth restriction. Int J Gynaecol Obstet 88:15–18
Young KH, Bazer FW, Simpkins JW et al (1987) Effects of early pregnancy and acute 17β-estradiol administration on porcine uterine secretion, cyclic nucleotides, and catecholamines. Endocrinology 120:254–263
Zeng X, Wang F, Fan X et al (2008) Dietary arginine supplementation during early pregnancy enhances embryonic survival in rats. J Nutr 138:1421–1425
Acknowledgments
This work was supported by Sustainability Strategy 2013–2014, from CODI University of Antioquia (UdeA), Medellín, Colombia Scholarship “Becas Doctorado UdeA 2014” (to YYL; PhD student in Veterinary Science, Faculty of Agrarian Science, Antioquia University) and by Agriculture and Food Research Initiative Competitive Grants (2011-67015-20028 and 2015-67015-23276) from the USDA National Institute of Food and Agriculture (to FWB and GW). Yasser Lenis is also a Research Fellow in the Department of Animal Science, Texas A&M University.
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This study involved an established cell line and did not require the use of animals.
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Lenis, Y.Y., Wang, X., Tang, W. et al. Effects of agmatine on secretion of interferon tau and catecholamines and expression of genes related to production of polyamines by ovine trophectoderm cells. Amino Acids 48, 2389–2399 (2016). https://doi.org/10.1007/s00726-016-2216-1
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DOI: https://doi.org/10.1007/s00726-016-2216-1