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Physiological importance of polyamines

  • Yasser Y. Lenis (a1) (a2) (a3) (a4), Mohammed A. Elmetwally (a2) (a3) (a5), Juan G. Maldonado-Estrada (a3) and Fuller W. Bazer (a2) (a3)

Summary

Polyamines are polycationic molecules that contain two or more amino groups (–NH3 +) and are present in all eukaryotic and prokaryotic cells. Polyamines are synthesized from arginine, ornithine, and proline, and from methionine as the methyl-group donor. In the traditional pathway for polyamine synthesis, arginase converts arginine into ornithine, which is decarboxylated by ornithine decarboxylase (ODC1) to generate putrescine. The latter is converted to spermidine and spermine. Recent studies have indicated the existence of ‘non-classical pathways’ for the generation of putrescine from arginine and proline in animal cells. Specifically, arginine decarboxylase (ADC) catalyzes the conversion of arginine into agmatine, which is hydrolyzed by agmatinase (AGMAT) to form putrescine. Additionally, proline is oxidized by proline oxidase to yield pyrroline-5-carboxylate, which undergoes transamination with glutamate to produce ornithine for decarboxylation by ODC1. Intracellular production of polyamines is controlled by antizymes binding to and inactivating ODC1. Polyamines exert effects that include stimulation of cell division and proliferation, gene expression for the survival of cells, DNA and protein synthesis, regulation of apoptosis, oxidative stress, angiogenesis, and cell–cell communication activity. Accordingly, polyamines are essential for early embryonic development and successful pregnancy outcome in mammals. In this paper the main concepts on the history, structure and molecular pathways of polyamines as well as their physiological role on angiogenesis, and reproductive physiology are reviewed.

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Corresponding author

All correspondence to: Yasser Y. Lenis. Research Group in Animal Science, Faculty of Agricultural Sciences, University of Applied and Environmental Sciences, Calle 222 #55–37, Bogota, Colombia. E-mail: yasser.lenis@udea.edu.co

References

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Allen, R.G. & Tresini, M. (2000). Oxidative stress and gene regulation. Free Radic. Biol. Med. 28, 463–99.
Ames, B.N., Donald, T.D. & Sanford, M.R. (1958). Presence of polyamines in certain bacterial viruses. Science 127, 814.
Arısan, E.D., Ajda, Ç. & Narçin, P.Ü. (2012). Polyamine depletion enhances the roscovitine-induced apoptosis through the activation of mitochondria in HCT116 colon carcinoma cells. Amino Acids 42, 655–65.
Bachrach, U. (2010). The early history of polyamine research. Plant Physiol. Biochem. 48, 490–5.
Bazer, F.W., Wu, G., Johnson, G.A., Kim, J. & Song, G. (2011). Uterine histotroph and conceptus development: select nutrients and secreted phosphoprotein 1 affect mechanistic target of rapamycin cell signaling in ewes. Biol. Reprod. 85, 1094–107.
Billington, D.C. (1991). Angiogenesis and its inhibition: potential new therapies in oncology and non-neoplastic diseases. Drug Des. Discov. 8, 335.
Boettcher, A. (1865). Farblose Krystalle eines eiweissartigen Korpers aus dem menschlichen Sperma dargestellt. Virchows Arch. Pathol. Anat. Physiol. Klin. Med. 32, 525–35.
Codoñer, F.P., Valls, B.V., Codoñer, A.A. & Eulalia, A.I. (2011). Oxidant mechanisms in childhood obesity: the link between inflammation and oxidative stress. Transl. Res. 158, 369–84.
Coffino, P. (2001). Regulation of cellular polyamines by antizyme. Nat. Rev. Mol. Cell. Biol. 2,188–94.
Conway, E.M., Désiré, C. & Peter, C. (2001). Molecular mechanisms of blood vessel growth. Cardiovasc. Res. 49, 507–21.
Demircan, S.S., Küçük, M., Nergiz Avcıoğlu, S., Zafer, E., Altınkaya, S.Ö., Bıçakçı, B. & Kurt, Ö. (2015). Comparison of maternal and umbilical cord blood HIF-1α and nitric oxide levels in early and late onset preeclamptic pregnancies. Gynecol. Endocrinol. 25,14.
Drolet, G., Dumbroff, E.B., Legge, R.L. & Thompson, J.E. (1986). Radical scavenging properties of polyamines. Phytochemistry 25, 367–71.
Dudley, H.W., Rosenheim, M.C. & Rosenheim, O. (1924). The chemical constitution of spermine. I. The isolation of spermine from animal tissues, and the preparation of its salts. Biochem. J. 18, 1263–72.
Finkel, T. & Nikki, J.H. (2000). Oxidants, oxidative stress and the biology of ageing. Nature 408, 239–47.
Grancara, S., Zonta, F., Ohkubo, S., Brunati, A.M., Agostinelli, E. & Toninello, A. (2015). Pathophysiological implications of mitochondrial oxidative stress mediated by mitochondriotropic agents and polyamines: the role of tyrosine phosphorylation. Amino Acids 47, 869–83.
Gray, C.A., Taylor, K.M., Ramsey, W.S. Hill, J.R., Bazer, F.W., Bartol, F.F. & Spencer, T.E. (2001). Endometrial glands are required for preimplantation conceptus elongation and survival. Biol. Reprod. 1, 1608–13.
Grillo, M.A. & Colombatto, S. (2004). Arginine revisited: minireview article. Amino Acids 26, 345–51.
Harari, P.M., Fuller, D.J. & Eugene, W.G. (1989). Heat shock stimulates polyamine oxidation by two distinct mechanisms in mammalian cell cultures. Int. J. Radiat. Oncol. Biol. Phys. 16, 451–7.
Herbst, E.J. & Esmond, E. S. (1948). Putrescine as a growth factor for Hemophilus parainfluenzae . J. Biol. Chem. 176, 989–90.
Hirst, D.G. & Flitney, F.W. (1997). The physiological importance and therapeutic potential of nitric oxide in the tumour-associated vasculature. In Bicknell, R., Lewis, C.E. & Ferrara, N. (eds), Tumor Angiogenesis. vol. 153–7, Oxford University Press.
Igarashi, K. & Kashiwagi, K. (2000). Polyamines: mysterious modulators of cellular functions. Biochem. Biophys. Res. Commun. 271, 559–64.
Igarashi, K. & Kashiwagi, K. (2015). Modulation of protein synthesis by polyamines. IUBMB Life 67, 160–9.
Jasnis, M.A., Klein, S., Monte, M., Davel, L., de Lustig, E.S. & Algranati, I.D. (1994). Polyamines prevent DFMO-mediated inhibition of angiogenesis. Cancer Lett. 79, 3943.
Joshi, M. (1997). The importance of l-arginine metabolism in melanoma: an hypothesis for the role of nitric oxide and polyamines in tumor angiogenesis. Free Radic. Biol. Med. 22, 573–8.
Kalač, P. (2013). Health effects and occurrence of dietary polyamines: a review for the period 2005–mid 2013. Food Chem. 161, 2739.
Kim, J.Y., Burghardt, R.C., Wu, G., Johnson, G.A., Spencer, T.E. & Bazer, F.W. (2011). Select nutrients in the ovine uterine lumen. VIII. Arginine stimulates proliferation of ovine trophectoderm cells through MTOR–RPS6K–RPS6 signaling cascade and synthesis of nitric oxide and polyamines. Biol. Reprod. 84, 70–8.
Knowles, R.G. & Salvador, M. (1994). Nitric oxide synthases in mammals. Biochem. J. 298, 249–58.
Kwon, H, Wu, G., Bazer, F.W. & Spencer, T.E. (2003). Developmental changes in polyamine levels and synthesis in the ovine conceptus. Biol. Reprod. 69, 16261634.
Ladenburg, A. & Abel, J. (1888). Ueber das Aethylenimin (Spermin?). Ber Deutsch Chem. Ges. 21, 758–66.
Lefèvre, P.L., Palin, M.F. & Murphy, B.D. (2011). Polyamines on the reproductive landscape. Endocr. Rev. 32, 694712.
Lenis, Y.Y., Olivera, M.A. & Tarazona, A.M. (2010). Molecular signals affecting PGF2α and PGE2 synthesis in bovine endometrium. Rev. Colomb. Cienc. Pecu. 23, 377–89.
Li, H., Meininger, C.J., Kelly, K.A., Hawker, J.R., Morris, S.M. & Wu, G. (2002). Activities of arginase I and II are limiting for endothelial cell proliferation. Am. J. Physiol. Regul. Integr. Comp. Physiol. 282, 64–9.
Li, X., Fan, X., Zheng, Z.H., Yang, X., Liu, Z., Gong, J.P. & Liang, H.P. (2013). [Protective effects of agmatine on lipopolysaccharide-induced acute hepatic injury in mice]. Zhonghua Wei Zhong Bing Ji Jiu Yi Xue [In Chinese] 25, 720–4.
Liu, Z., Hou, F., Jin, H., Xiao, Y., Fan, X., Yang, X., Yan, J. & Liang, H. (2015). [Effects of agmatine on excessive inflammatory reaction and proliferation of splenic cells in mice with trauma]. Zhonghua Wei Zhong Bing Ji Jiu Yi Xue [In Chinese] 27,110–4.
Medina, M.A., Quesada, A.R., de Castro, I.N. & Sánchez, J.F. (1999). Histamine, polyamines, and cancer. Biochem. Pharmacol. 57, 1341–4.
Moinard, C., Cynober, L. & de Bandt, J.P. (2005). Polyamines: metabolism and implications in human diseases. Clin. Nutr. 24, 184–97.
Morbidelli, L.U., Chang, C.H., Douglas, J.G., Granger, H.J., Ledda, F.A. & Ziche, M.A. (1996). Nitric oxide mediates mitogenic effect of VEGF on coronary venular endothelium. Am. J. Physiol. Heart Circ. Physiol. 270, 411–5.
Neufeld, G., Cohen, T., Gengrinovitch, S. & Poltorak, Z. (1999). Vascular endothelial growth factor (VEGF) and its receptors. FASEB J. 13, 922.
Papapetropoulos, A., García, C.G., Madri, J.A. & Sessa, W.C. (1997). Nitric oxide production contributes to the angiogenic properties of vascular endothelial growth factor in human endothelial cells. J. Clin. Invest. 100, 3131–9.
Pegg, A.E. (2009). Mammalian polyamine metabolism and function. IUBMB Life 61, 880–94.
Pipili, S.E., Sakkoula, E., Haralabopoulos, G., Andriopoulou, P., Peristeris, P. & Maragoudakis, M.E. (1994). Evidence that nitric oxide is an endogenous antiangiogenic mediator. Br. J. Pharmacol. 111, 894902.
Rhee, H.J., Kim, E.J. & Lee, J.K. (2007). Physiological polyamines: simple primordial stress molecules. J. Cell. Mol. Med. 11, 685703.
Rider, J.E., Hacker, A., Mackintosh, C.A., Pegg, A.E., Woster, P.M. & Casero, J.R. (2007). Spermine and spermidine mediate protection against oxidative damage caused by hydrogen peroxide. Amino Acids 33, 231–40.
Tabor, H., Celia, W. & Sanford, M. (1961). Rosenthal. The biochemistry of the polyamines: spermidine and spermine. Annu. Rev. Biochem. 30, 579604.
Tadolini, B., Cabrini, L., Landi, L., Varani, E. & Pasquali, P. (1984). Polyamine binding to phospholipid vesicles and inhibition of lipid peroxidation. Biochem. Biophys. Res. Commun. 122, 550–5.
Takahashi, Y., Mai, M. & Nishioka, K. (2000). α-Difluoromethylornithine induces apoptosis as well as anti-angiogenesis in the inhibition of tumor growth and metastasis in a human gastric cancer model. Int. J. Cancer 85, 243–7.
Takigawa, M., Enomoto, M., Nishida, Y., Pan, H.O., Kinoshita, A. & Suzuki, F. (1990a). Tumor angiogenesis and polyamines: α-difluoromethylornithine, an irreversible inhibitor of ornithine decarboxylase, inhibits B16 melanoma-induced angiogenesis in ovo and the proliferation of vascular endothelial cells in vitro . Cancer Res. 50, 4131–8.
Takigawa, M., Nishida, Y., Suzuki, F., Kishi, J.I., Yamashita, K. & Hayakawa, T. (1990b). Induction of angiogenesis in chick yolk-sac membrane by polyamines and its inhibition by tissue inhibitors of metalloproteinases (TIMP and TIMP-2). Biochem. Biophys. Res. Commun. 171, 1264–71.
Tarazona, A.M., Olivera, M.A., Lenis, Y.Y. (2010). Rol de la mitocondria y el estrés oxidativo en el bloqueo del desarrollo de embriones bovinos producidos in vitro . Arch. Med. Vet. 42, 125–33.
Tiburcio, A.F., Altabella, T., Bitrián, M., Alcázar, R. (2014). The roles of polyamines during the lifespan of plants: from development to stress. Planta 240, 118.
Tkachenko, A., Nesterova, L. & Pshenichnov, M. (2001). The role of the natural polyamine putrescine in defense against oxidative stress in Escherichia coli . Arch. Microbiol. 176, 155–7.
Vauquelin, L.N. (1791). Experiences sur le sperme humain. Ann. Chim. 9, 6480.
Venuti, A., Paolini, F., Nasir, L., Corteggio, A., Roperto, S., Campo, M.S. & Borzacchiello, G. (2011). Papillomavirus E5: the smallest oncoprotein with many functions. Mol. Cancer 10, 140.
Wang, X., Ikeguchi, Y., McCloskey, D.E., Nelson, P. & Pegg, A.E. (2004). Spermine synthesis is required for normal viability, growth, and fertility in the mouse. J. Biol. Chem. 279, 51370–5.
Wang, J.F., Su, R.B., Wu, N., Xu, B., Lu, X.Q., Liu, Y. & Li, J. (2005). Inhibitory effect of agmatine on proliferation of tumor cells by modulation of polyamine metabolism. Acta Pharmacol. Sin. 26, 616–22.
Wang, X., Wei, Y., Dunlap, K.A., Lin, G., Satterfield, M.C., Burghardt, R.C., Wu, G. & Bazer, F.W. (2014). Arginine decarboxylase and agmatinase: an alternative pathway for de novo biosynthesis of polyamines for development of mammalian conceptuses. Biol. Reprod. 90, 84.
Weis, S.M. & Cheresh, D.A. (2011). Tumor angiogenesis: molecular pathways and therapeutic targets. Nature Med. 17, 1359–70.
Wu, G., Pond, W.G., Flynn, S.P., Ott, T.L. & Bazer, F.W. (1998). Maternal dietary protein deficiency decreases nitric oxide synthase and ornithine decarboxylase activities in placenta and endometrium of pigs during early gestation. J. Nutr. 128, 2395–402.
Zauberman, H., Michaelson, I.C., Bergmann, F. & Maurice, D.M. (1969). Stimulation of neovascularization of the cornea by biogenic amines. Exp. Eye Res. 8, 7783.
Ziche, M., Morbidelli, L., Masini, E., Amerini, S., Granger, H.J., Maggi, C.A., Geppetti, P. & Ledda, F. (1994). Nitric oxide mediates angiogenesis in vivo and endothelial cell growth and migration in vitro promoted by substance P. J. Clin. Invest. 94, 2036–44.

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Physiological importance of polyamines

  • Yasser Y. Lenis (a1) (a2) (a3) (a4), Mohammed A. Elmetwally (a2) (a3) (a5), Juan G. Maldonado-Estrada (a3) and Fuller W. Bazer (a2) (a3)

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