Abstract
The polyamines putrescine, spermidine and spermine are natural components of all living cells. Although their exact cellular functions are still largely unknown, a constant supply of these compounds is required for mammalian cell proliferation to occur. Studies with animals displaying genetically altered polyamine metabolism have shown that polymines are intimately involved in the development of diverse tumors, putrescine apparently has specific role in skin physiology and neuroprotection and the higher polyamines spermidine and spermine are required for the maintenance of pancreatic integrity and liver regeneration. In the absence of ongoing polyamine biosynthesis, murine embryogenesis does not proceed beyond the blastocyst stage. The last years have also witnessed the appearance of the first reports linking genetically altered polyamine metabolism to human diseases.
Keywords: Polyamines, transgenic, mouse, rat, knockout
References
- 1. Jänne, J , Alhonen, L , Pietilä, M , Keinänen, TA . Genetic approaches to the cellular functions of polyamines in mammals. Eur J Biochem. 2004; 271: 877–94. [DOI] [PubMed] [Google Scholar]
- 2. Thomas, T , Thomas, TJ . Polyamine metabolism and cancer. J Cell Mol Med. 2003; 7: 113–26. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3. Pless, M , Belhadj, K , Menssen, HD , Kern, W , Coiffier, B , Wolf, J , Herrmann, R , Thiel, E , Bootle, D , Sklenar, I , Muller, C , Choi, L , Porter, C , Capdeville, R . Clinical efficacy, tolerability, and safety of SAM486A, a novel polyamine biosynthesis inhibitor, in patients with redlapsed or refractory non‐Hodgkin's lymphoma: results from a phase II multicenter study. Clin Cancer Res. 2004; 10: 1299–305. [DOI] [PubMed] [Google Scholar]
- 4. Wolff, AC , Armstrong, DK , Casero, RA Jr , Davidson, NE . A Phase II study of the polyamine analog N1, N11‐diethyl‐norspermine (DENSpm) daily for five days every 21 days in patients with previously treated metastatic breast cancer. Clin Cancer Res. 2003; 9: 5922–8. [PubMed] [Google Scholar]
- 5. Russell, D , Snyder, SH . Amine synthesis in rapidly growing tissues: ornithine decarboxylase activity in regenerating rat liver, chick embryo, and various tumors. Proc Natl Acad Sci USA. 1968; 60: 1420–7. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6. Jänne, J , Raina, A . Stimulation of spermidine synthesis in the regenerating rat liver: relation to increased ornithine decarboxylase activity. Acta Chemd Scand. 1968; 22: 1349–51. [DOI] [PubMed] [Google Scholar]
- 7. Casero, RA , Pegg, AE . Spermidine/spermine N1‐acetyl‐transferase the turning point in polyamine metabolism. FASEB J. 1993; 7: 653–61. [PubMed] [Google Scholar]
- 8. Hölttä, E . Oxidation of spermidine and spermine in rat liver: purification and properties of polyamine oxidase. Biochemistry 1977; 16: 91–100. [DOI] [PubMed] [Google Scholar]
- 9. Wang, Y , de Vereux, W , Woster, PM , Stewart, TM , Hacker, A , Casero, RA Jr . Colning and characterization of a human polyamine oxidase that is inducible by polyamine analogue exposure. Cancer Res. 2001; 61: 5370–3. [PubMed] [Google Scholar]
- 10. Vujcic, S , Diegelman, P , Bacchi, CJ , Kramer, DL , Porter, CW . Identification and characterization of a novel flavincontaining spermine oxidase of mammalian cell origin, Biochem J. 2002; 367: 665–75. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11. Heller, JS , Fong, WF , Canellakis, ES . Induction of a protein inhibitor to ornithine decarboxylase by the end products of its reaction. Proc Natl Acad Sci USA. 1976; 73: 1858–62. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 12. Hayashi, S , Murakami, Y , Matsufuji, S . Ornithine decarboxylase antizyme: a novel type of regulatory protein, Trends Biochem Sci. 1996; 21: 27–30. [PubMed] [Google Scholar]
- 13. Howell, ML , Schroth, GP , Ho, PS . Sequence‐dependent effects of spermine on the thermodynamics of the B‐DNA to Z‐DNA transition. Biochemistry 1996; 35: 15373–82. [DOI] [PubMed] [Google Scholar]
- 14. Matsufuji, S , Matsufuji, T , Miyazaki, Y , Murakami, Y , Atkins, JF , Gesteland, RF , Hayashi, S‐I . Autoregulatory frameshifting in decoding mammalian ornithine decarboxylase antizyme. Cell 1995; 80: 51–60. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 15. Park, MH , Cooper, HL , Folk, JE . Identification of hypusine, an unusual amino acid, in protein from human lymphocytes and of spermidine as its biosynthetic precrusor, Proc Natl Acad Sci USA. 1981; 78: 2869–73. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 16. Park, MH , Wolff, EC , Folk, JE . Is hypusine essential for eukaryotic cell proliferation Trends Biochem Sci. 1993; 18: 475–479. [DOI] [PubMed] [Google Scholar]
- 17. Järvinen, A , Grigorenko, N , Khomutov, AR , Hyvönen, MT , Vimari, A , Vepsäläinen, J , Sinervirta, R , Keinänen, TA , Vujcic, S , Alhonen, L , Porter, CW , Jänne, J . Metabolic stability of α ‐Methylated Polyamine Derivatives and their use as substitutes for the natural polyamines. J Biol Chem. 2005; 280: 6595–601. [DOI] [PubMed] [Google Scholar]
- 18. Wallace, HM , Fraser, AV , Hughes, A . A Perspective of polyamine metabolism. Biochem J. 2003; 376: 1–14. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 19. Halmekytö, M , Alhonen, L , Wahlfors, J , Sinervirta, R , Eloranta, T , Jänne, J . Characterization of a transgenic mice aberrantly expressing human ornithine decarboxylase gene. J Biol Chem 1991; 278: 895–8. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 20. Halmekytö, M , Hyttinen, J‐M , Sinervirta, R , Utriainen, M , Myöhänen, S , Voipio, H‐M , Wahlfors, J , Syrjänen, S , Syrjänen, K , Alhonen, L , Jänne, J . Transgenic mice aberrantly expressing human ornithine decarboxylase gene. J Biol Chem. 1991; 266: 19746–51. [PubMed] [Google Scholar]
- 21. Moshier, JA , Dosescu, J , Skunca, M , Luk, GD . Transformation of NIH/3T3 cells by ornithine decarboxylase overexpression. Cancer Res. 1993; 53: 2618–22. [PubMed] [Google Scholar]
- 22. Alhonen, L , Halmekytö, M , Kosma, V‐M , Wahlfors, J , Kauppinen, R , Jänne, J . Life‐long over‐expression of ornithine decarboxylase (ODC) gene in transgenic mice does not lead to generally enhanced tumorigenesis or neuronal degeneration. Int J Cancer 1995; 63: 402–4. [DOI] [PubMed] [Google Scholar]
- 23. Halmekytö, M , Alhonen, L , Alakuijala, L , Jänne, J . Transgenic mice overproducing putrescine in their tissues do not convert the diamine into higher polyamines. Biochem J. 1993; 291: 505–8. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 24. Gritli‐Linde, A , Björkman, U , Holm, I , Törnell, J , Linde, A . Effects of chronically elevated growth hormone levels on polyamine metabolism in elderly transgenic mice. Mol Cell Endocrinol. 1997; 126: 49–58. [DOI] [PubMed] [Google Scholar]
- 25. Kilpeläinen, PT , Saarimies, J , Kontusaari, SI , Järvinen, MJ , Soler, AP , Kallioinen, MJ , Hietala, OA . Abnormal ornithine decarboxylase activity in transgenic mice increases tumor formation and infertility. Int J Biochem Cell Biol. 2001; 33: 507–20. [DOI] [PubMed] [Google Scholar]
- 26. Halmekytö, M , Syrjänen, K , Jänne, J , Alhonen, L . Enhanced papilloma formation in response to skin tumor promotion in transgenic mice overexpressing the human ornithine decarboxylase gene. Biochem Biophys Res Commun. 1992; 187: 493–7. [DOI] [PubMed] [Google Scholar]
- 27. Megosh, L , Gilmour, SK , Rosson, D , Soler, AP , Blessing, M , Sawicki, JA , O'Brien, TG . Increased frequency of spontaneous skin tumors in transgenic mice which overexpress ornithine decarboxylase. Cancer Res. 1995; 55: 4205–9. [PubMed] [Google Scholar]
- 28. O'Brien, TG , Megosh, LC , Gilliard, G , Soler, AP . Ornithine decarboxylase overexpression is a sufficient condition for tumor promotion in mouse skin. Cancer Res. 1997; 57: 2630–7. [PubMed] [Google Scholar]
- 29. Soler, AP , Gilliard, G , Megosh, L , George K, TG OB . Polyamines regulate expression of the neoplastic phenotype in mouse skin. Cancer Res. 1998; 58: 1654–9. [PubMed] [Google Scholar]
- 30. Smith, MK , Trempus, CS , Gilmour, SK . Co‐operation between follicular ornithine decarboxylase and v‐Ha‐ras induces spontaneous papillomas and malignant conversion in transgenic skin. Carcinogenesis 1998; 19: 1409–15. [DOI] [PubMed] [Google Scholar]
- 31. Ahmad, N , Gilliam, AC , Katiyar, SK , O'Brien, TG , Mukhtar, H . A definitive role of ornithine decarboxylase in photocarcinogenesis. Am J Pathol. 2001; 159: 885–92. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 32. Guo, Y , Cleveland, JL , O'Brien, TG . Haploinsufficiency for odc modifies mouse skin tumor susceptibility. Cancer Res. 2005; 65: 1146–9. [DOI] [PubMed] [Google Scholar]
- 33. Feith, DJ , Shantz, LM , Pegg, AE . Targeted antizyme expression in the skin of transgenic mice reduces tumor promoter induction of ornithine decarboxylase and decreases sensitivity to chemical carcinogenesis. Cancer Res. 2001; 61: 6073–81. [PubMed] [Google Scholar]
- 34. Pietilä, M , Alhonen, L , Halmekytö, M , Kanter, P , Jänne, J , Porter, CW . Activation of polyamine catabolism profoundly alters tissue polyamine pools and affects hair growth and female fertility in transgenic mice overexpressing spermidine/spermine N1‐acetyltransferase. J Biol Chem. 1997; 272: 18746–51. [DOI] [PubMed] [Google Scholar]
- 35. Pietilä, M , Parkkinen, JJ , Alhonen, L , Jänne, J . Relation of skin polyamines to the hairless phenotype in transgenic mice overexpressing sper‐midine/spermine N1‐acetyl‐transferase. J Invest Dermatol. 2001; 116: 801–5. [DOI] [PubMed] [Google Scholar]
- 36. Coleman, CS , Pegg, AE , Megosh, LC , Guo, Y , Sawicki, JA , O'Brien, TG . Targeted expression of spermidine/spermine N1‐acetyltransferase increases susceptibility to chemically induced skin carcinogenesis. Carcinogenesis 2002; 23: 359–64. [DOI] [PubMed] [Google Scholar]
- 37. Lu, YP , Lou, YR , Lin, Y , Shih, WJ , Huang, MT , Yang, CS , Conney, AH . Inhibitory effects of orally administered green tea, black tea, and caffeine on skin carcinogenesis in mice previously treated with ultraviolet B light (high‐risk mice): relationship to decreased tissue fat. Cancer Res. 2001; 61: 5002–9. [PubMed] [Google Scholar]
- 38. Fong, LY , Feith, DJ , Pegg, AE . Antizyme overexpression in transgenic mice reduces cell proliferation, increases apoptosis, and reduces N‐nitrosomethylbenzylamine‐ induced forestomach carcinogenesis. Cancer Res. 2003; 63: 3945–54. [PubMed] [Google Scholar]
- 39. Su, LK , Kinzler, KW , Vogelstein, B , Preisinger, AC , Moser, AR , Luongo, C , Gould, KA , Dove, WF . Multiple intestinal neoplasia caused by a mutation in the murine homolog of the APC gene. Science 1992; 256: 668–70. [DOI] [PubMed] [Google Scholar]
- 40. Moser, AR , Pitot, HC , Dove, WF . A dominant mutation that predisposes to multiple intestinal neoplasia in the mouse. Science 1990; 247: 322–4. [DOI] [PubMed] [Google Scholar]
- 41. Tucker, JM , Murphy, JT , Kisiel, N , Diegelman, P , Barbour, KW , Davis, C , Medda, M , Alhonen, L , Jänne, J , Kramer, DL , Porter, CW , Berger, FG . Potent modulation of intestinal tumorigenesis in Apc Min+ mice by the polyamine catabolic enzyme spermidine/spermine N1‐acetyltransferase. Cancer Res. 2005; 65: 5390–8. [DOI] [PubMed] [Google Scholar]
- 42. Jacoby, RF , Cole, CE , Tutsch, K , Newton, MA , Kelloff, G , Hawk, ET , Lubet, RA . Chemopreventive efficacy of combined piroxicam and difluoromethylornithine treatment of Apc mutant Min mouse adenomas, and selective toxicity against Apc mutant embryos. Cancer Res. 2000; 60: 1864–70. [PubMed] [Google Scholar]
- 43. Kee, K , Foster, BA , Merali, S , Kramer, DL , Hensen, ML , Diegelman, P , Kisiel, N , Vujcic, S , Mazurchuk, RV , Porter, CW . Activated polyamine catabolism depletes acetyl‐CoA pools and suppresses prostate tumor growth in TRAMP mice. J Biol Chem. 2004; 279: 40076–83. [DOI] [PubMed] [Google Scholar]
- 44. Bello‐Fernandez, C , Packham, G , Cleveland, JL . The ornithine decarboxylase gene is a transcriptional target of c‐Myc. Proc Natl Acad Sci USA. 1993; 90: 7804–8. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 45. Nilsson, JA , Nilsson, LM , Keller, U , Yokota, Y , Boyd, K , Cleveland, JL . Id2 is dispensable for myc‐induced lymphomagenesis. Cancer Res. 2004; 64: 7296–301. [DOI] [PubMed] [Google Scholar]
- 46. Nilsson, JA , Keller, UB , Baudino, TA , Yang, C , Norton, S , Old, JA , Nilsson, LM , Neale, G , Kramer, DL , Porter, CW , Cleveland, JL . Targeting ornithine decarboxylase in Myc‐ induced lymphomagenesis prevents tumor formation. Cancer Cell 2005; 7: 433–44. [DOI] [PubMed] [Google Scholar]
- 47. Soler, AP , Gilliard, G , Megosh, LC , O'Brien, TG . Modulation of murine hair follicle function by alterations in ornithine decarboxylase activity. J Invest Dermatol. 1996; 106: 1108–13. [DOI] [PubMed] [Google Scholar]
- 48. Pietilä, M , Pirinen, E , Keskitalo, S , Juutinen, S , Pasonen‐Seppänen, S , Keinänen, T , Alhonen, L , Jänne, J . Disturbed keratinocyte differentiation in transgenic mice and organotypic keratinocyte cultures as a result of spermidine/spermine N‐acetyltransferase overexpression. J Invest Dermatol. 2005; 124: 596–601. [DOI] [PubMed] [Google Scholar]
- 49. Pirinen, E , Heikkinen, S , Virkamäki, A , Hohtola, E , Pietilä, M , Jänne, J , Laakso, M . Severely reduced white fat deposits without a defect in insulin sensitivity in transgenic mice overexpressing spermidine/spermine N1‐acetyltransferase. Diabetologia 2002; 45: A83. [Google Scholar]
- 50. Hakovirta, H , Keiski, A , Toppari, J , Halmekytö, M , Alhonen, L , Jänne, J , Parvinen, M . Polyamines and regulation of spermatogenesis: selective stimulation of late spermatogonia in transgenic mice overexpressing the human ornithine decarboxylase gene. Mol Endocrinol. 1993; 7: 1430–6. [DOI] [PubMed] [Google Scholar]
- 51. Ivanov, IP , Rohrwasser, A , Terreros, DA , Gesteland, RF , Atkins, JF . Discovery of a spermatogenesis stage‐specific ornithine decarboxylase antizyme: antizyme 3. Proc Natl Acad Sci USA. 2000; 97: 4808–13. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 52. Min, SH , Simmen, RC , Alhonen, L , Halmekytö, M , Porter, CW , Jänne, J , Simmen, FA . Altered levels of growth‐related and novel gene transcripts in reproductive and other tissues of female mice over‐expressing spermidine/spermine N1‐acetyltransferase (SSAT). J Biol Chem. 2002; 277: 3647–57. [DOI] [PubMed] [Google Scholar]
- 53. Kauppinen, RA , Alhonen, LI . Transgenic animals as models in the study of the neurobiological role of polyamines. Progr Neurobiol. 1995; 47: 545–63. [DOI] [PubMed] [Google Scholar]
- 54. Najm, I , EI‐Skaf, G , Tocco, G , van de Rklish, P , Lynch, G , Baudry, M . Seizure activity‐induced changes in polyamine metabolism and neuronal pathology during the postnatal period in rat brain. Dev Brain Res. 1992; 69: 11–21. [DOI] [PubMed] [Google Scholar]
- 55. Halonen, T , Sivenius, J , Miettinen, R , Halmekytö, M , Kauppinen, R , Sinervirta, R , Alakuijala, L , Alhonen, L , MacDonald, E , Jänne, J , Riekkinen, P Sr . Elevated seiqure threshold and impaired spatial learning in transgenic mice with putrescine overproduction in the brain. Eur J Neurosci. 1993; 5: 1233–9. [DOI] [PubMed] [Google Scholar]
- 56. Lukkarinen, J , Kauppinen, RA , Koistinaho, J , Halmekytö, M , Alhonen, L , Jänne, J . Cerebral energy metabolism and immediate early gene induction following severe incomplete ischaemia in transgenic mice overexpressing the human ornithine decarboxylase gene: evidence that putrescine is not neurotoxic in vivo . Eur J Neurosci. 1995; 7: 1840–9. [DOI] [PubMed] [Google Scholar]
- 57. Lukkarinen, J , Gröhn, O , Sinervirta, R , Järvinen, A , Kauppinen, RA , Jänne, J , Alhonen, L . Transgenic rats as models for studying the role of ornithine decarboxylase expression in permanent middle cerebral artery occlusion. Stroke 1997; 28: 639–45. [DOI] [PubMed] [Google Scholar]
- 58. Lukkarinen, JA , Kauppinen, RA , Gröhn, OHJ , Oja, JME , Sinervirta, R , Alhonen, LI , Jänne, J . Neuroprotective role of ornithine decarboxylase activation in transient cerebral focal ischemia: A study using ornithine decarboxylase‐overexpressing transgenic rats. Eur J Neurosci. 1998; 10: 2046–55. [DOI] [PubMed] [Google Scholar]
- 59. Lukkarinen, JA , Gröhn, OH , Alhonen, LI , Jänne, J , Kauppinen, RA . Enhanced ornithine decarboxylase activity is associated with attenuated rate of damage evolution and reduction of infarct volume in transient middle cerebral artery occlusion in the rat. Brain Res. 1999; 826: 325–9. [DOI] [PubMed] [Google Scholar]
- 60. Kaasinen, K , Koistinaho, J , Alhonen, L , Jänne, J . Overexpression of spermidine/spermine N1‐acetyltransferase in transgenic mice protects the animals from kainate‐induced toxicity. Eur J Neurosci. 2000; 12: 540–8. [DOI] [PubMed] [Google Scholar]
- 61. Kaasinen, SK , Gröhn, OH , Keinänen, TA , Alhonen, L , Jänne, J . Over‐expression of spermidine/spermine N1‐acetyltransferase elevates the threshold to pentylenetetra‐zol‐induced seizure activity in transgenic mice. Exp Neurol. 2003; 183: 645–52. [DOI] [PubMed] [Google Scholar]
- 62. Kaasinen, SK , Oksman, M , Alhonen, L , Tanila, H , Jänne, J . Sper‐midine/spermine N1‐acetyltransferase overexpression in mice induces hypoactivity and spatial learning impairment. Pharmacol Biochem Behav. 2004; 78: 3545. [DOI] [PubMed] [Google Scholar]
- 63. Williams, K , Romano, C , Molinoff, PB . Effects of polyamines on the binding of [3H]MK‐801 to the N‐methyl‐D‐aspartate receptor: pharmacological evidence for the existence of a polyamine recognition site. Mol Pharmacol. 1989; 36: 575–81. [PubMed] [Google Scholar]
- 64. Williams, K , Dawson, VL , Romano, C , Dichter, MA , Molinoff, PB . Characterization of polyamines having agonist, antagonist, and inverse effects at the polyamine recognition site of the NMDA receptor. Neuron 1990; 5: 199–208. [DOI] [PubMed] [Google Scholar]
- 65. Paschen, W . Polyamine metabolism in different pathological states of the brain. Mol Chem Neuropathol. 1992; 16: 241–71. [DOI] [PubMed] [Google Scholar]
- 66. Hämäläinen, R . Über die quantitative Bestimmung des Spermins im Organismus und sein Vorkommen in meschlichen Geweben und Körperflüssigkeiten. Acta Soc Med “Duodecim” Series A. 1947; 23: 97–165. [Google Scholar]
- 67. Rosenthal, SM , Tabor, CW . The pharmacology of spermine and spermidine. Distribution and excretion. J Pharmacol Exp Ther. 1956; 116: 131–8. [PubMed] [Google Scholar]
- 68. Morisset, J , Grondin, G . Implication of ornithine decarboxylase and polyamines in pancreatic growth of neonatal rats. Pancreas 1987; 2: 303–11. [DOI] [PubMed] [Google Scholar]
- 69. Haarstad, H , Skei, T , Petersen, H . Inhibition of polyamine synthesis by α‐difluoromethyl‐ornithine and its effect on pancreatic secretion and growth in the rat. Scand J Gastroenterol. 1989; 24: 733–44. [DOI] [PubMed] [Google Scholar]
- 70. Alhonen, L , Parkkinen, JJ , Keinänen, T , Sinervirta, R , Herzig, KH , Jänne, J . Activation of polyamine catabolism in transgenic rats induces acute pancreatitis. Proc Natl Acad Sci USA. 2000; 97: 8290–5. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 71. Räsänen, TL , Alhonen, L , Sinervirta, R , Keinänen, T , Herzig, KH , Suppola, S , Khomutov, AR , Vepsäläinen, J , Jänne, J . A polyamine analogue prevents acute pancreatitis and restores early liver regeneration in transgenic rats with activated polyamine catabolism. J Biol Chem. 2002; 277: 39867–72. [DOI] [PubMed] [Google Scholar]
- 72. Herzig, KH , Jänne, J , Alhonen, L . Acute pancreatitis induced by activation of the polyamine catabolism in gene‐modified mice and rats overexpressing spermidine/spermine N1‐acetyltransferase. Scand J Gastroenterol. 2005; 40: 120–1. [DOI] [PubMed] [Google Scholar]
- 73. Räsänen, TL , Alhonen, L , Sinervirta, R , Uimari, A , Kaasinen, K , Keinänen, T , Herzig, KH , Jänne, J . Gossypol activates pancreatic polyamine catabolism in normal rats and induces acute pancreatitis in transgenic rats over‐expressing spermidine/spermine N1‐acetyltransferase. Scand J Gastroenterol. 2003; 38: 787–93. [DOI] [PubMed] [Google Scholar]
- 74. Jänne, J . Studies on the biosynthetic pathway of polyamines in rat liver. Acta Physiol Scand Suppl. 1967; 300: 1–71. [PubMed] [Google Scholar]
- 75. Harik, SI , Hollenberg, MD , Snyder, SH . α‐hydrazinoornithine blocks net synthesis of putrescine but not of RNA and DNA. Nature 1974. 249: 250–1. [DOI] [PubMed] [Google Scholar]
- 76. Pösö, H , Pegg, AE . Effect of α‐difluoromethylornithine on polyamine and DNA synthesis in regenerating rat liver. Biochim Biophys. Acta 1982; 696: 179–86. [DOI] [PubMed] [Google Scholar]
- 77. Arora, V , Iversen, PL , Ebadi, M . Manipulation of metallothionein expression in the regenerating rat liver using antisense oligonucleotides. Biochem Biophys Res Commun. 1998; 246: 711–8. [DOI] [PubMed] [Google Scholar]
- 78. Tsujikawa, K , Suzuki, N , Sagawa, K , Itoh, M , Sugiyama, T , Kohama, Y , Otaki, N , Kimura, M , Mimura, T . Induction and subcellular localization of metallothionein in regenerating rat liver. Eur J Cell Biol. 1994; 63: 240–6. [PubMed] [Google Scholar]
- 79. Alhonen, L , Räsänen, TL , Sinervirta, R , Parkkinen, JJ , Korhonen, VP , Pietilä, M , Jänne, J . Polyamines are required for the initiation of rat liver regeneration. Biochem J. 2002; 362: 149–53. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 80. Byers, TL , Lakanen, JR , Coward, JK , Pegg, AE . The role of hypusine depletion in cytostasis induced by S‐adenosyl‐L‐methionine decarboxylase inhibition: new evidence provided by 1‐methylspermidine and 1,12‐dimethylspermine. Biochem J. 1994; 303: 363–8. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 81. Mackintosh, CA , Feith, DJ , Shantz, LM , Pegg, AE . Overexpression of antizyme in the hearts of transgenic mice prevents the isoprenaline‐induced increase in cardiac ornithine decarboxylase activity and polyamines, but does not prevent cardiac hypertrophy. Biochem J. 2000; 350: 645–53. [PMC free article] [PubMed] [Google Scholar]
- 82. Bartolome, JV , Trepanier, PA , Chait, EA , Slotkin, TA . Role of polyamines in isoproterenol‐induced cardiac hypertrophy: Effects of alphadifluoromethylornithine, an irreversible inhibitor of ornithine decarboxylase. J Mol Cell Cardiol. 1982; 14: 461–6. [DOI] [PubMed] [Google Scholar]
- 83. Jenkinson, CP , Grody, WW , Cederbaum, SD . Comparative properties of arginases. Comp Biochem Physiol Biochem Mol Biol. 1996; B 114: 107–32. [DOI] [PubMed] [Google Scholar]
- 84. Shi, O , Morris, SM Jr , Zoghbi, H , Porter, CW , O'Brien, WE . Generation of a mouse model for arginase II deficiency by targeted disruption of the arginase II gene. Mol Cell Biol. 2001; 21: 811–3. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 85. Pendeville, H , Carpino, N , Marine, J‐C , Takahashi, Y , Muller, M , Martial, JA , Cleveland, JL . The ornithine decarboxylase gene is essential for cell survival during early murine development. Mol Cell Biol. 2001; 21: 6549–58. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 86. Nishimura, K , Nakatsu, F , Kashiwagi, K , Ohno, H , Saito, T , Igarashi, K . Essential role of S‐adenosylmethionine decarboxylase in mouse embryonic development. Genes Cells 2002; 7: 41–7. [DOI] [PubMed] [Google Scholar]
- 87. Persson, K , Holm, I , Heby, O . Cloning and sequencing of an intronless Mouse S‐adenosylmethionine decarboxylase gene coding for a functional enzyme strongly expressed in the liver. J Biol Chem. 1995; 270: 5642–8. [DOI] [PubMed] [Google Scholar]
- 88. Korhonen, V‐P , Niiranen, K , Halmekytö, M , Pietilä, M , Diegelman, P , Parkkinen, JJ , Eloranta, T , Porter, CW , Alhonen, L , Jänne, J . Spermine deficiency resulting from targeted disruption of the spermine synthase gene in embryonic stem cells leads to enhanced sensitivity to antiproliferative drugs. Mol Pharmacol. 2001; 59: 231–8. [DOI] [PubMed] [Google Scholar]
- 89. Lorenz, B , Francis, F , Gempel, K , Boddrich, A , Josten, M , Schmahl, W , Schmidt, J , Lehrach, H , Meitinger, T , Strom, TM . Spermine deficiency in Gy mice caused by deletion of the spermine synthase gene. Hum Mol Genet. 1998; 7: 541–7. [DOI] [PubMed] [Google Scholar]
- 90. Lyon, MF , Scriver, CR , Baker, LR , van Enhouse, HS , Kronick, J , Mandla, S . The Gy mutation: another cause of X‐linked hypophosphatemia in mouse. Proc Natl Acad Sci USA. 1986; 83: 4899–903. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 91. Wang, X , Ikeguchi, Y , McCloskey, DE , Nelson, P , Pegg, AE . Spermine synthesis is required for normal viability, growth, and fertility in the mouse. J Biol Chem. 2004; 279: 51370–5. [DOI] [PubMed] [Google Scholar]
- 92. Lopatin, AN , Shantz, LM , Mackintosh, CA , Nichols, CG , Pegg, AE . Modulation of potassium channels in the hearts of transgenic and mutant mice with altered polyamine biosynthesis. J Mol Cell Cardiol. 2000; 32: 2007–24. [DOI] [PubMed] [Google Scholar]
- 93. Ikeguchi, Y , Wang, X , McCloskey, DE , Coleman, CS , Nelson, P , Hu, G , Shantz, LM , Pegg, AE . Characterization of transgenic mice with widespread overexpression of spermine synthase. Biochem J. 2004; 381: 701–7. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 94. Niiranen, K , Pietilä, M , Pirttilä, TJ , Järvinen, A , Halmekytö, M , Korhonen, VP , Keinänen, TA , Alhonen, L , Jänne, J . Targeted disruption of spermidine/spermine N1‐acetyltransferase gene in mouse embryonic stem cells. Effects on polyamine homeostasis and sensitivity to polyamine analogues. J Biol Chem. 2002; 277: 25323–8. [DOI] [PubMed] [Google Scholar]
- 95. Tamori, A , Nishiguchi, S , Kuroki, T , Koh, N , Kobayashi, K , Yano, Y , Otani, S . Point mutation of ornithine decarboxylase gene in human hepatocellular carcinoma. Cell Res. 1995; 55: 3500–3. [PubMed] [Google Scholar]
- 96. Rogers, S , Wells, R , Rechsteiner, M . Amino acid sequences common to rapidly degraded proteins: the PEST hypothesis. Science 1986; 234: 364–8. [DOI] [PubMed] [Google Scholar]
- 97. Martinez, ME , O'Brien, TG , Fultz, KE , Babbar, N , Yerushalmi, H , Qu, N , Guo, Y , Boorman, D , Einspahr, J , Alberts, DS , Gerner, EW . Pronounced reduction in adenoma recurrence associated with aspirin use and a polymorphism in the ornithine decarboxylase gene. Proc Natl Acad Sci USA. 2003; 100: 7859–64. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 98. Cason, AL , Ikeguchi, Y , Skinner, C , Wood, TC , Holden, KR , Lubs, HA , Martinez, F , Simensen, RJ , Stevenson, RE , Pegg, AE , Schwartz, CE . X‐linked spermine synthase gene (SMS) defect: the first polyamine deficiency syndrome. Eur J Hum Genet. 2003; 11: 937–44. [DOI] [PubMed] [Google Scholar]
- 99. Gimelli, G , Giglio, S , Zuffardi, O , Alhonen, L , Suppola, S , Cusano, R , Lo Nigro, C , Gatti, R , Ravazzolo, R , Seri, M . Gene dosage of the sper‐midine/spermine N(1)‐acetyltransferase (SSAT) gene with putrescine accumulation in a patient with a Xp21.1p22.12 duplication and keratosis follicularis spinulosa decalvans (KFSD). Hum Genet. 2002; 111: 235–41. [DOI] [PubMed] [Google Scholar]