Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
권호 표지
DOI QR코드

DOI QR Code

Polyamines and Their Metabolites as Diagnostic Markers of Human Diseases

  • Park, Myung Hee (Oral and Pharyngeal Cancer Branch, NIDCR, National Institutes of Health) ;
  • Igarashi, Kazuei (Graduate School of Pharmaceutical Sciences, Chiba University)
  • Received : 2012.12.10
  • Accepted : 2013.01.04
  • Published : 2013.01.31
Download PDF
⟨ Previous Next ⟩

Abstract

Polyamines, putrescine, spermidine and spermine, are ubiquitous in living cells and are essential for eukaryotic cell growth. These polycations interact with negatively charged molecules such as DNA, RNA, acidic proteins and phospholipids and modulate various cellular functions including macromolecular synthesis. Dysregulation of the polyamine pathway leads to pathological conditions including cancer, inflammation, stroke, renal failure and diabetes. Increase in polyamines and polyamine synthesis enzymes is often associated with tumor growth, and urinary and plasma contents of polyamines and their metabolites have been investigated as diagnostic markers for cancers. Of these, diacetylated derivatives of spermidine and spermine are elevated in the urine of cancer patients and present potential markers for early detection. Enhanced catabolism of cellular polyamines by polyamine oxidases (PAO), spermine oxidase (SMO) or acetylpolyamine oxidase (AcPAO), increases cellular oxidative stress and generates hydrogen peroxide and a reactive toxic metabolite, acrolein, which covalently incorporates into lysine residues of cellular proteins. Levels of protein-conjuagated acrolein (PC-Acro) and polyamine oxidizing enzymes were increased in the locus of brain infarction and in plasma in a mouse model of stroke and also in the plasma of stroke patients. When the combined measurements of PC-Acro, interleukin 6 (IL-6), and C-reactive protein (CRP) were evaluated, even silent brain infarction (SBI) was detected with high sensitivity and specificity. Considering that there are no reliable biochemical markers for early stage of stroke, PC-Acro and PAOs present promising markers. Thus the polyamine metabolites in plasma or urine provide useful tools in early diagnosis of cancer and stroke.

Keywords

References

  1. Agostinelli, E., Tempera, G., Viceconte, N., Saccoccio, S., Battaglia, V., Grancara, S., Toninello, A. and Stevanato, R. (2010) Potential anticancer application of polyamine oxidation products formed by amine oxidase: a new therapeutic approach. Amino Acids 38, 353-368. https://doi.org/10.1007/s00726-009-0431-8
  2. Auvinen, M., Paasinen, A., Andersson, L. C. and Holtta, E. (1992) Ornithine decarboxylase activity is critical for cell transformation. Nature 360, 355-358. https://doi.org/10.1038/360355a0
  3. Babbar, N., Murray-Stewart, T. and Casero, R. A. Jr. (2007) Inflammation and polyamine catabolism: the good, the bad and the ugly. Biochem. Soc. Trans. 35, 300-304. https://doi.org/10.1042/BST0350300
  4. Bachrach, U. (2005) Naturally occurring polyamines: interaction with macromolecules. Curr. Protein Pept. Sci. 6, 559-566. https://doi.org/10.2174/138920305774933240
  5. Becerra-Solano, L. E., Butler, J., Castaneda-Cisneros, G., McCloskey, D. E., Wang, X., Pegg, A. E., Schwartz, C. E., Sanchez-Corona, J. and Garcia-Ortiz, J. E. (2009) A missense mutation, p.V132G, in the X-linked spermine synthase gene (SMS) causes Snyder-Robinson syndrome. Am. J. Med. Genet. A 149A, 328-335. https://doi.org/10.1002/ajmg.a.32641
  6. Bokura, H., Kobayashi, S., Yamaguchi, S., Iijima, K., Nagai, A., Toyoda, G., Oguro, H. and Takahashi, K. (2006) Silent brain infarction and subcortical white matter lesions increase the risk of stroke and mortality: a prospective cohort study. J. Stroke Cerebrovasc. Dis. 15, 57-63. https://doi.org/10.1016/j.jstrokecerebrovasdis.2005.11.001
  7. Byers, T. L., Lakanen, J. R., Coward, J. K. and Pegg, A. E. (1994) 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. 303, 363-368. https://doi.org/10.1042/bj3030363
  8. Casero, R. A. Jr. and Marton, L. J. (2007) Targeting polyamine metabolism and function in cancer and other hyperproliferative diseases. Nat. Rev. Drug Discov. 6, 373-390. https://doi.org/10.1038/nrd2243
  9. Cerrada-Gimenez, M., Pietila, M., Loimas, S., Pirinen, E., Hyvonen, M. T., Keinanen, T. A., Janne, J. and Alhonen, L. (2011) Continuous oxidative stress due to activation of polyamine catabolism accelerates aging and protects against hepatotoxic insults. Transgenic Res. 20, 387-396. https://doi.org/10.1007/s11248-010-9422-5
  10. Clifford, A., Morgan, D., Yuspa, S. H., Soler, A. P. and Gilmour, S. (1995) Role of ornithine decarboxylase in epidermal tumorigenesis. Cancer Res. 55, 1680-1686.
  11. Coffino, P. (2001) Regulation of cellular polyamines by antizyme. Nat. Rev. Mol. Cell Biol. 2, 188-194. https://doi.org/10.1038/35056508
  12. Dingledine, R., Borges, K., Bowie, D. and Traynelis, S. F. (1999) The glutamate receptor ion channels. Pharmacol. Rev. 51, 7-61.
  13. Fleidervish, I. A., Libman, L., Katz, E. and Gutnick, M. J. (2008) Endogenous polyamines regulate cortical neuronal excitability by blocking voltage-gated Na+ channels. Proc. Natl. Acad. Sci. USA 105, 18994-18999. https://doi.org/10.1073/pnas.0803464105
  14. Fujita, K., Murakami, Y. and Hayashi, S. (1982) A macromolecular inhibitor of the antizyme to ornithine decarboxylase. Biochem. J. 204, 647-652. https://doi.org/10.1042/bj2040647
  15. Gerner, E. W. and Meyskens, F. L. Jr. (2004). Polyamines and cancer: old molecules, new understanding. Nat. Rev. Cancer 4, 781-792. https://doi.org/10.1038/nrc1454
  16. Gerner, E. W. and Meyskens, F. L. Jr. (2009) Combination chemoprevention for colon cancer targeting polyamine synthesis and inflammation. Clin. Cancer Res. 15, 758-761. https://doi.org/10.1158/1078-0432.CCR-08-2235
  17. Gimelli, G., Giglio, S., Zuffardi, O., Alhonen, L., Suppola, S., Cusano, R., Lo Nigro, C., Gatti, R., Ravazzolo, R. and Seri, M. (2002) Gene dosage of the spermidine/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. 111, 235-241. https://doi.org/10.1007/s00439-002-0791-6
  18. Giorgio, M., Trinei, M., Migliaccio, E. and Pelicci, P. G. (2007) Hydrogen peroxide: a metabolic by-product or a common mediator of ageing signals? Nat. Rev. Mol. Cell Biol. 8, 722-728. https://doi.org/10.1038/nrm2240
  19. Gomez, M. and Hellstrand, P. (1995) Effects of polyamines on voltage-activated calcium channels in guinea-pig intestinal smooth muscle. Pflugers Arch. 430, 501-507. https://doi.org/10.1007/BF00373886
  20. Herr, H. W., Kleinert, E. L., Conti, P. S., Burchenal, J. H. and Whitmore, W.F., Jr. (1984) Effects of alpha-difluoromethylornithine and methylglyoxal bis(guanylhydrazone) on the growth of experimental renal adenocarcinoma in mice. Cancer Res. 44, 4382-4385.
  21. Higgins, M. L., Tillman, M. C., Rupp, J. P. and Leach, F. R. (1969) The effect of polyamines on cell culture cells. J. Cell. Physiol. 74, 149-154.
  22. Hiramatsu, K., Takahashi, K., Yamaguchi, T., Matsumoto, H., Miyamoto, H., Tanaka, S., Tanaka, C., Tamamori, Y., Imajo, M., Kawaguchi, M. et al. (2005) N(1),N(12)-Diacetylspermine as a sensitive and specific novel marker for early- and late-stage colorectal and breast cancers. Clin. Cancer Res. 11, 2986-2990. https://doi.org/10.1158/1078-0432.CCR-04-2275
  23. Hobbs, C. A., Paul, B. A. and Gilmour, S. K. (2002) Deregulation of polyamine biosynthesis alters intrinsic histone acetyltransferase and deacetylase activities in murine skin and tumors. Cancer Res. 62, 67-74.
  24. Hoshi, T., Kitagawa, K., Yamagami, H., Furukado, S., Hougaku, H. and Hori, M. (2005) Relations of serum high-sensitivity C-reactive protein and interleukin-6 levels with silent brain infarction. Stroke 36, 768-772. https://doi.org/10.1161/01.STR.0000158915.28329.51
  25. Hyvonen, M. T., Keinanen, T. A., Cerrada-Gimenez, M., Sinervirta, R., Grigorenko, N., Khomutov, A. R., Vepsalainen, J., Alhonen, L. and Janne, J. (2007) Role of hypusinated eukaryotic translation initiation factor 5A in polyamine depletion-induced cytostasis. J. Biol. Chem. 282, 34700-34706. https://doi.org/10.1074/jbc.M704282200
  26. Igarashi, K. and Kashiwagi, K. (2000) Polyamines: mysterious modulators of cellular functions. Biochem. Biophys. Res. Commun. 271, 559-564. https://doi.org/10.1006/bbrc.2000.2601
  27. Igarashi, K. and Kashiwagi, K. (2010) Modulation of cellular function by polyamines. Int. J. Biochem. Cell Biol. 42, 39-51. https://doi.org/10.1016/j.biocel.2009.07.009
  28. Igarashi, K. and Kashiwagi, K. (2011a) Use of polyamine metabolites as markers for stroke and renal failure. Methods Mol. Biol. 720, 395-408. https://doi.org/10.1007/978-1-61779-034-8_25
  29. Igarashi, K. and Kashiwagi, K. (2011b) Protein-conjugated acrolein as a biochemical marker of brain infarction. Mol. Nutr. Food Res. 55, 1332-1341. https://doi.org/10.1002/mnfr.201100068
  30. Igarashi, K., Ueda, S., Yoshida, K. and Kashiwagi, K. (2006) Polyamines in renal failure. Amino Acids 31, 477-483. https://doi.org/10.1007/s00726-006-0264-7
  31. Inoue, K., Matsumoto, M., Shono, T., Toyokawa, S. and Moriki, A. (2007) Increased intima media thickness and atherosclerotic plaques in the carotid artery as risk factors for silent brain infarcts. J. Stroke Cerebrovasc. Dis. 16, 14-20. https://doi.org/10.1016/j.jstrokecerebrovasdis.2006.08.001
  32. Ivanov, I. P., Gesteland, R. F., Matsufuji, S. and Atkins, J. F. (1998) Programmed frameshifting in the synthesis of mammalian antizyme is +1 in mammals, predominantly +1 in fission yeast, but -2 in budding yeast. RNA 4, 1230-1238. https://doi.org/10.1017/S1355838298980864
  33. Janne, J., Alhonen, L., Pietila, M. and Keinanen, T. A. (2004) Genetic approaches to the cellular functions of polyamines in mammals. Eur. J. Biochem. 271, 877-894. https://doi.org/10.1111/j.1432-1033.2004.04009.x
  34. Jin, L., Miyazaki, M., Mizuno, S., Takigawa, M., Hirose, T., Nishimura, K., Toida, T., Williams, K., Kashiwagi, K. and Igarashi, K. (2008) The pore region of N-methyl-D-aspartate receptors differentially influences stimulation and block by spermine. J. Pharmacol. Exp. Ther. 327, 68-77. https://doi.org/10.1124/jpet.108.140459
  35. Joe, Y. A., Wolff, E. C. and Park, M. H. (1995) Cloning and expression of human deoxyhypusine synthase cDNA. Structure-function studies with the recombinant enzyme and mutant proteins. J. Biol. Chem. 270, 22386-22392. https://doi.org/10.1074/jbc.270.38.22386
  36. Kaasinen, S. K., Oksman, M., Alhonen, L., Tanila, H. and Janne, J. (2004) Spermidine/spermine N1-acetyltransferase overexpression in mice induces hypoactivity and spatial learning impairment. Pharmacol. Biochem. Behav. 78, 35-45. https://doi.org/10.1016/j.pbb.2004.02.001
  37. Kawakita, M. and Hiramatsu, K. (2006) Diacetylated derivatives of spermine and spermidine as novel promising tumor markers. J. Biochem. 139, 315-322. https://doi.org/10.1093/jb/mvj068
  38. Kramer, D. L., Diegelman, P., Jell, J., Vujcic, S., Merali, S. and Porter, C. W. (2008) Polyamine acetylation modulates polyamine metabolic flux, a prelude to broader metabolic consequences. J. Biol. Chem. 283, 4241-4251. https://doi.org/10.1074/jbc.M706806200
  39. Kramer, D. L., Paul, B. and Porter, C. W. (1985) Effect of pretreatment with alpha-difluoromethylornithine on the selectivity of methylglyoxal bis(guanylhydrazone) for tumor tissue in L1210 leukemic mice. Cancer Res. 45, 2512-2515.
  40. Landau, G., Ran, A., Bercovich, Z., Feldmesser, E., Horn-Saban, S., Korkotian, E., Jacob-Hirsh, J., Rechavi, G., Ron, D. and Kahana, C. (2012) Expression profiling and biochemical analysis suggest stress response as a potential mechanism inhibiting proliferation of polyamine-depleted cells. J. Biol. Chem. 287, 35825-35837. https://doi.org/10.1074/jbc.M112.381335
  41. Lawson, K., Larentowicz, L., Laury-Kleintop, L. and Gilmour, S. K. (2005) B23 is a downstream target of polyamine-modulated CK2. Mol. Cell. Biochem. 274, 103-114. https://doi.org/10.1007/s11010-005-3066-4
  42. Linden, A. (2006) Measuring diagnostic and predictive accuracy in disease management: an introduction to receiver operating characteristic (ROC) analysis. J. Eval. Clin. Pract. 12, 132-139. https://doi.org/10.1111/j.1365-2753.2005.00598.x
  43. Lopez, O. L., Jagust, W. J., Dulberg, C., Becker, J. T., DeKosky, S. T., Fitzpatrick, A., Breitner, J., Lyketsos, C., Jones, B., Kawas, C. et al. (2003) Risk factors for mild cognitive impairment in the Cardiovascular Health Study Cognition Study: part 2. Arch. Neurol. 60, 1394-1399. https://doi.org/10.1001/archneur.60.10.1394
  44. Mamont, P. S., Duchesne, M. C., Grove, J. and Bey, P. (1978) Anti-proliferative properties of DL-alpha-difluoromethyl ornithine in cultured cells. A consequence of the irreversible inhibition of ornithine decarboxylase. Biochem. Biophys. Res. Commun. 81, 58-66. https://doi.org/10.1016/0006-291X(78)91630-3
  45. Mandal, S., Mandal, A., Johansson, H. E., Orjalo, A. V. and Park, M. H. (2013) Depletion of cellular polyamines, spermidine and spermine, causes a total arrest in translation and growth in mammalian cells. Proc. Natl. Acad. Sci. USA in press published ahead of print January 23, 2013, doi:10.1073/pnas.1219002110
  46. Matthews, H. R. (1993) Polyamines, chromatin structure and transcription. Bioessays 15, 561-566. https://doi.org/10.1002/bies.950150811
  47. Minois, N., Carmona-Gutierrez, D. and Madeo, F. (2011) Polyamines in aging and disease. Aging (Albany NY) 3, 716-732.
  48. Mize, G. J., Ruan, H., Low, J. J. and Morris, D. R. (1998) The inhibitory upstream open reading frame from mammalian S-adenosylmethionine decarboxylase mRNA has a strict sequence specificity in critical positions. J. Biol. Chem. 273, 32500-32505. https://doi.org/10.1074/jbc.273.49.32500
  49. Nakaike, S., Kashiwagi, K., Terao, K., Iio, K. and Igarashi, K. (1988) Combined use of alpha-difluoromethylornithine and an inhibitor of S-adenosylmethionine decarboxylase in mice bearing P388 leukemia or Lewis lung carcinoma. Jpn. J. Cancer Res. 79, 501-508. https://doi.org/10.1111/j.1349-7006.1988.tb01619.x
  50. Nishimura, K., Lee, S. B., Park, J. H. and Park, M. H. (2012) Essential role of eIF5A-1 and deoxyhypusine synthase in mouse embryonic development. Amino Acids 42, 703-710. https://doi.org/10.1007/s00726-011-0986-z
  51. Nishimura, K., Murozumi, K., Shirahata, A., Park, M. H., Kashiwagi, K. and Igarashi, K. (2005) Independent roles of eIF5A and polyamines in cell proliferation. Biochem. J. 385, 779-785. https://doi.org/10.1042/BJ20041477
  52. Nishimura, K., Nakatsu, F., Kashiwagi, K., Ohno, H., Saito, T. and Igarashi, K. (2002) Essential role of S-adenosylmethionine decarboxylase in mouse embryonic development. Genes Cells 7, 41-47. https://doi.org/10.1046/j.1356-9597.2001.00494.x
  53. Nishimura, K., Shiina, R., Kashiwagi, K. and Igarashi, K. (2006) Decrease in polyamines with aging and their ingestion from food and drink. J. Biochem. 139, 81-90. https://doi.org/10.1093/jb/mvj003
  54. Ogasawara, T., Ito, K. and Igarashi, K. (1989) Effect of polyamines on globin synthesis in a rabbit reticulocyte polyamine-free protein synthetic system. J. Biochem. 105, 164-167. https://doi.org/10.1093/oxfordjournals.jbchem.a122633
  55. Oredsson, S. M., Alm, K., Dahlberg, E., Holst, C. M., Johansson, V. M., Myhre, L. and Soderstjerna, E. (2007) Inhibition of cell proliferation and induction of apoptosis by N1,N11-diethylnorspermine-induced polyamine pool reduction. Biochem. Soc. Trans. 35, 405-409. https://doi.org/10.1042/BST0350405
  56. Oredsson, S. M., Anehus, S. and Heby, O. (1984) Reversal of the growth inhibitory effect of alpha-difluoromethylornithine by putrescine but not by other divalent cations. Mol. Cell. Biochem. 64, 163-172.
  57. Park, J. H., Aravind, L., Wolff, E. C., Kaevel, J., Kim, Y. S. and Park, M. H. (2006) Molecular cloning, expression, and structural prediction of deoxyhypusine hydroxylase: a HEAT-repeat-containing metallo-enzyme. Proc. Natl. Acad. Sci. USA 103, 51-56. https://doi.org/10.1073/pnas.0509348102
  58. Park, M. H. (2006) The post-translational synthesis of a polyamine-derived amino acid, hypusine, in the eukaryotic translation initiation factor 5A (eIF5A). J. Biochem. 139, 161-169. https://doi.org/10.1093/jb/mvj034
  59. Park, M. H., Nishimura, K., Zanelli, C. F. and Valentini, S. R. (2010) Functional significance of eIF5A and its hypusine modification in eukaryotes. Amino Acids 38, 491-500. https://doi.org/10.1007/s00726-009-0408-7
  60. Patel, A. R. and Wang, J. Y. (1997) Polyamines modulate transcription but not posttranscription of c-myc and c-jun in IEC-6 cells. Am. J. Physiol. 273, C1020-1029. https://doi.org/10.1152/ajpcell.1997.273.3.C1020
  61. Pegg, A. E. (2008) Spermidine/spermine-N1-acetyltransferase: a key metabolic regulator. Am. J. Physiol. Endocrinol. Metab. 294, E995-1010. https://doi.org/10.1152/ajpendo.90217.2008
  62. Pegg, A. E. (2009) Mammalian polyamine metabolism and function. IUBMB Life 61, 880-894. https://doi.org/10.1002/iub.230
  63. Pegg, A. E. and Casero, R. A. Jr. (2011) Current status of the polyamine research field. Methods Mol. Biol. 720, 3-35. https://doi.org/10.1007/978-1-61779-034-8_1
  64. Pendeville, H., Carpino, N., Marine, J. C., Takahashi, Y., Muller, M., Martial, J. A. and Cleveland, J. L. (2001) The ornithine decarboxylase gene is essential for cell survival during early murine development. Mol. Cell. Biol. 21, 6549-6558. https://doi.org/10.1128/MCB.21.19.6549-6558.2001
  65. Quigley, G. J., Teeter, M. M. and Rich, A. (1978) Structural analysis of spermine and magnesium ion binding to yeast phenylalanine transfer RNA. Proc. Natl. Acad. Sci. USA 75, 64-68. https://doi.org/10.1073/pnas.75.1.64
  66. Russell, D. and Snyder, S. H. (1968) Amine synthesis in rapidly growing tissues: ornithine decarboxylase activity in regenerating rat liver, chick embryo, and various tumors. Proc. Natl. Acad. Sci. USA 60, 1420-1427. https://doi.org/10.1073/pnas.60.4.1420
  67. Russell, D. H., Levy, C. C., Schimpff, S. C. and Hawk, I. A. (1971) Urinary polyamines in cancer patients. Cancer Res. 31, 1555-1558.
  68. Saiki, R., Nishimura, K., Ishii, I., Omura, T., Okuyama, S., Kashiwagi, K. and Igarashi, K. (2009) Intense correlation between brain infarction and protein-conjugated acrolein. Stroke 40, 3356-3361. https://doi.org/10.1161/STROKEAHA.109.553248
  69. Saiki, R., Park, H., Ishii, I., Yoshida, M., Nishimura, K., Toida, T., Tatsukawa, H., Kojima, S., Ikeguchi, Y., Pegg, A. E. et al. (2011) Brain infarction correlates more closely with acrolein than with reactive oxygen species. Biochem. Biophys. Res. Commun. 404, 1044-1049. https://doi.org/10.1016/j.bbrc.2010.12.107
  70. Seppanen, P., Alhonen-Hongisto, L. and Janne, J. (1983) Combined use of 2-difluoro-methylornithine and methylglyoxal bis (guanylhydrazone) in normal and leukemia-bearing mice. Cancer Lett. 18, 1-10. https://doi.org/10.1016/0304-3835(83)90111-8
  71. Sequeira, A., Gwadry, F. G., Ffrench-Mullen, J. M., Canetti, L., Gingras, Y., Casero, R. A. Jr., Rouleau, G., Benkelfat, C. and Turecki, G. (2006) Implication of SSAT by gene expression and genetic variation in suicide and major depression. Arch. Gen. Psychiatry 63, 35-48. https://doi.org/10.1001/archpsyc.63.1.35
  72. Sharmin, S., Sakata, K., Kashiwagi, K., Ueda, S., Iwasaki, S., Shirahata, A. and Igarashi, K. (2001) Polyamine cytotoxicity in the presence of bovine serum amine oxidase. Biochem. Biophys. Res. Commun. 282, 228-235. https://doi.org/10.1006/bbrc.2001.4569
  73. Shin, J., Shen, F. and Huguenard, J. R. (2005) Polyamines modulate AMPA receptor-dependent synaptic responses in immature layer v pyramidal neurons. J. Neurophysiol. 93, 2634-2643. https://doi.org/10.1152/jn.01054.2004
  74. Soda, K., Dobashi, Y., Kano, Y., Tsujinaka, S. and Konishi, F. (2009) Polyamine-rich food decreases age-associated pathology and mortality in aged mice. Exp. Gerontol. 44, 727-732. https://doi.org/10.1016/j.exger.2009.08.013
  75. Stanfield, P. R. and Sutcliffe, M. J. (2003) Spermine is fit to block inward rectifier (Kir) channels. J. Gen. Physiol. 122, 481-484. https://doi.org/10.1085/jgp.200308957
  76. Stevens, J. F. and Maier, C. S. (2008) Acrolein: sources, metabolism, and biomolecular interactions relevant to human health and disease. Mol. Nutr. Food Res. 52, 7-25. https://doi.org/10.1002/mnfr.200700412
  77. Tabor, C. W. and Tabor, H. (1984) Polyamines. Ann. Rev. Biochem. 53, 749-790. https://doi.org/10.1146/annurev.bi.53.070184.003533
  78. Thomas, T. and Thomas, T. J. (2001) Polyamines in cell growth and cell death: molecular mechanisms and therapeutic applications. Cell. Mol. Life Sci. 58, 244-258. https://doi.org/10.1007/PL00000852
  79. Tomitori, H., Usui, T., Saeki, N., Ueda, S., Kase, H., Nishimura, K., Kashiwagi, K. and Igarashi, K. (2005) Polyamine oxidase and acrolein as novel biochemical markers for diagnosis of cerebral stroke. Stroke 36, 2609-2613. https://doi.org/10.1161/01.STR.0000190004.36793.2d
  80. Uchida, K., Kanematsu, M., Morimitsu, Y., Osawa, T., Noguchi, N. and Niki, E. (1998) Acrolein is a product of lipid peroxidation reaction. Formation of free acrolein and its conjugate with lysine residues in oxidized low density lipoproteins. J. Biol. Chem. 273, 16058-16066. https://doi.org/10.1074/jbc.273.26.16058
  81. Vermeer, S. E., Longstreth, W. T. Jr. and Koudstaal, P. J. (2007) Silent brain infarcts: a systematic review. Lancet Neurol. 6, 611-619. https://doi.org/10.1016/S1474-4422(07)70170-9
  82. Wallace, H. M., Duthie, J., Evans, D. M., Lamond, S., Nicoll, K. M. and Heys, S. D. (2000) Alterations in polyamine catabolic enzymes in human breast cancer tissue. Clin. Cancer Res. 6, 3657-3661.
  83. Wang, X., Levic, S., Gratton, M. A., Doyle, K. J., Yamoah, E. N. and Pegg, A. E. (2009) Spermine synthase deficiency leads to deafness and a profound sensitivity to alpha-difluoromethylornithine. J. Biol. Chem. 284, 930-937. https://doi.org/10.1074/jbc.M807758200
  84. Wang, Y., Xiao, L., Thiagalingam, A., Nelkin, B. D. and Casero, R. A. Jr. (1998) The identification of a cis-element and a trans-acting factor involved in the response to polyamines and polyamine analogues in the regulation of the human spermidine/spermine N1-acetyltransferase gene transcription. J. Biol. Chem. 273, 34623-34630. https://doi.org/10.1074/jbc.273.51.34623
  85. Watanabe, S., Kusama-Eguchi, K., Kobayashi, H. and Igarashi, K. (1991) Estimation of polyamine binding to macromolecules and ATP in bovine lymphocytes and rat liver. J. Biol. Chem. 266, 20803-20809.
  86. Williams-Ashman, H. G. and Schenone, A. (1972) Methyl glyoxal bis(guanylhydrazone) as a potent inhibitor of mammalian and yeast S-adenosylmethionine decarboxylases. Biochem. Biophys. Res. Commun. 46, 288-295. https://doi.org/10.1016/0006-291X(72)90661-4
  87. Yoshida, M., Higashi, K., Kobayashi, E., Saeki, N., Wakui, K., Kusaka, T., Takizawa, H., Kashiwado, K., Suzuki, N., Fukuda, K. et al. (2010) Correlation between images of silent brain infarction, carotid atherosclerosis and white matter hyperintensity, and plasma levels of acrolein, IL-6 and CRP. Atherosclerosis 211, 475-479. https://doi.org/10.1016/j.atherosclerosis.2010.03.031
  88. Yoshida, M., Tomitori, H., Machi, Y., Hagihara, M., Higashi, K., Goda, H., Ohya, T., Niitsu, M., Kashiwagi, K. and Igarashi, K. (2009) Acrolein toxicity: Comparison with reactive oxygen species. Biochem. Biophys. Res. Commun. 378, 313-318. https://doi.org/10.1016/j.bbrc.2008.11.054

Cited by

  1. Self-Immolative Polycations as Gene Delivery Vectors and Prodrugs Targeting Polyamine Metabolism in Cancer vol.12, pp.2, 2015, https://doi.org/10.1021/mp500469n
  2. Distinguishing mild cognitive impairment from Alzheimer's disease with acrolein metabolites and creatinine in urine vol.441, 2015, https://doi.org/10.1016/j.cca.2014.12.023
  3. Low-molecular-weight regulators of biogenic polyamine metabolism affect cytokine production and expression of hepatitis С virus proteins in Huh7.5 human hepatocarcinoma cells vol.51, pp.3, 2017, https://doi.org/10.1134/S0026893317030128
  4. Astrocyte-Dependent Vulnerability to Excitotoxicity in Spermine Oxidase-Overexpressing Mouse vol.18, pp.1, 2016, https://doi.org/10.1007/s12017-015-8377-3
  5. Metabolic Consequences of Chronic Alcohol Abuse in Non-Smokers: A Pilot Study vol.10, pp.6, 2015, https://doi.org/10.1371/journal.pone.0129570
  6. Molecularly imprinted fluorescent chemosensor synthesized using quinoline-modified-β-cyclodextrin as monomer for spermidine recognition vol.5, pp.68, 2015, https://doi.org/10.1039/C5RA07761C
  7. Low-level maternal exposure to nicotine associates with significant metabolic perturbations in second-trimester amniotic fluid vol.107, 2017, https://doi.org/10.1016/j.envint.2017.07.019
  8. Synthesis, structure and antiproliferative activity of chiral polyamines based on a 2-azanorbornane skeleton vol.27, pp.16, 2016, https://doi.org/10.1016/j.tetasy.2016.06.009
  9. Gene and protein expressions and metabolomics exhibit activated redox signaling and wnt/β-catenin pathway are associated with metabolite dysfunction in patients with chronic kidney disease vol.12, 2017, https://doi.org/10.1016/j.redox.2017.03.017
  10. Functions of Polyamines in Mammals vol.291, pp.29, 2016, https://doi.org/10.1074/jbc.R116.731661
  11. Extracellular polyamines-induced proliferation and migration of cancer cells by ODC, SSAT, and Akt1-mediated pathway vol.28, pp.4, 2017, https://doi.org/10.1097/CAD.0000000000000465
  12. In vitro Metabolomic Approaches to Investigating the Potential Biological Effects of Phenolic Compounds: An Update vol.15, pp.4, 2017, https://doi.org/10.1016/j.gpb.2016.12.007
  13. Evaluation of dementia by acrolein, amyloid-β and creatinine vol.450, 2015, https://doi.org/10.1016/j.cca.2015.07.017
  14. Decrease in acrolein toxicity based on the decline of polyamine oxidases vol.79, 2016, https://doi.org/10.1016/j.biocel.2016.08.039
  15. Functional Role of Milk Fat Globule-Epidermal Growth Factor VIII in Macrophage-Mediated Inflammatory Responses and Inflammatory/Autoimmune Diseases vol.2016, 2016, https://doi.org/10.1155/2016/5628486
  16. A useful procedure for detection of polyamines in biological samples as a potential diagnostic tool in cancer diagnosis vol.37, pp.1, 2017, https://doi.org/10.1186/s41241-017-0032-x
  17. Untargeted and targeted methodologies in the study of tea (Camellia sinensis L.) vol.63, 2014, https://doi.org/10.1016/j.foodres.2014.03.070
  18. Putrescine oxidase/peroxidase-co-immobilized and mediator-less mesoporous microelectrode for diffusion-controlled steady-state amperometric detection of putrescine 2017, https://doi.org/10.1016/j.jelechem.2017.09.056
  19. Functional Roles of Syk in Macrophage-Mediated Inflammatory Responses vol.2014, 2014, https://doi.org/10.1155/2014/270302
  20. Urinary Polyamines as Biomarkers for Ovarian Cancer vol.27, pp.7, 2017, https://doi.org/10.1097/IGC.0000000000001031
  21. AP-1-Targeted Inhibition of Macrophage Function and Lipopolysaccharide/D-Galactosamine-Induced Hepatitis by Phyllanthus acidus Methanolic Extract vol.43, pp.06, 2015, https://doi.org/10.1142/S0192415X15500652
  22. Anthocyanins Protect SK-N-SH Cells Against Acrolein-Induced Toxicity by Preserving the Cellular Redox State vol.50, pp.4, 2016, https://doi.org/10.3233/JAD-150770
  23. Altering the Mitochondrial Fatty Acid Synthesis (mtFASII) Pathway Modulates Cellular Metabolic States and Bioactive Lipid Profiles as Revealed by Metabolomic Profiling vol.11, pp.3, 2016, https://doi.org/10.1371/journal.pone.0151171
  24. Determination of putrescine, cadaverine, spermidine and spermine in different chemical matrices by high performance liquid chromatography–electrospray ionization–ion trap tandem mass spectrometry (HPLC–ESI–ITMS/MS) vol.1002, 2015, https://doi.org/10.1016/j.jchromb.2015.08.036
  25. HIV-Tat Induces the Nrf2/ARE Pathway through NMDA Receptor-Elicited Spermine Oxidase Activation in Human Neuroblastoma Cells vol.11, pp.2, 2016, https://doi.org/10.1371/journal.pone.0149802
  26. Drug Resistance in Mycobacterium tuberculosis vol.147, pp.4, 2015, https://doi.org/10.1378/chest.14-1286
  27. The metabolomic detection of lung cancer biomarkers in sputum vol.94, 2016, https://doi.org/10.1016/j.lungcan.2016.02.006
  28. Atractylodes macrocephala Koidz stimulates intestinal epithelial cell migration through a polyamine dependent mechanism vol.159, 2015, https://doi.org/10.1016/j.jep.2014.10.059
  29. Untargeted Metabolomics To Ascertain Antibiotic Modes of Action vol.60, pp.4, 2016, https://doi.org/10.1128/AAC.02109-15
  30. Skeletal Muscle Pathophysiology: The Emerging Role of Spermine Oxidase and Spermidine vol.6, pp.1, 2018, https://doi.org/10.3390/medsci6010014
  31. Spermidine in health and disease vol.359, pp.6374, 2018, https://doi.org/10.1126/science.aan2788
  32. Endogenous and food-derived polyamines: determination by electrochemical sensing vol.50, pp.9, 2018, https://doi.org/10.1007/s00726-018-2617-4
  33. Spectroscopic methods to analyze drug metabolites vol.41, pp.4, 2018, https://doi.org/10.1007/s12272-018-1010-x
  34. Polyamine patterns in plasma of patients with systemic lupus erythematosus and fever vol.27, pp.6, 2018, https://doi.org/10.1177/0961203317751860
  35. The Involvement of Arginase and Nitric Oxide Synthase in Breast Cancer Development: Arginase and NO Synthase as Therapeutic Targets in Cancer vol.2018, pp.2314-6141, 2018, https://doi.org/10.1155/2018/8696923
  36. Metabiotics: The Functional Metabolic Signatures of Probiotics: Current State-of-Art and Future Research Priorities—Metabiotics: Probiotics Effector Molecules vol.09, pp.04, 2018, https://doi.org/10.4236/abb.2018.94012
  37. Programmable RNA-based systems for sensing and diagnostic applications pp.1618-2650, 2019, https://doi.org/10.1007/s00216-019-01622-7
  38. Polyamines, folic acid supplementation and cancerogenesis vol.28, pp.3, 2013, https://doi.org/10.1515/pterid-2017-0012
  39. Functionalized gold nanoparticle-enhanced competitive assay for sensitive small-molecule metabolite detection using surface plasmon resonance vol.143, pp.1, 2013, https://doi.org/10.1039/c7an01680h
  40. Importance of an Aldehyde Dehydrogenase 2 Polymorphism in Preventive Medicine vol.73, pp.1, 2013, https://doi.org/10.1265/jjh.73.9
  41. Design and Mechanism of GABA Aminotransferase Inactivators. Treatments for Epilepsies and Addictions vol.118, pp.7, 2013, https://doi.org/10.1021/acs.chemrev.8b00009
  42. Discovery and antitumor evaluation of novel inhibitors of spermine oxidase vol.34, pp.1, 2013, https://doi.org/10.1080/14756366.2019.1621863
  43. Polyamines in Food vol.6, pp.None, 2013, https://doi.org/10.3389/fnut.2019.00108
  44. Tricarboxylic acid cycle activity suppresses acetylation of mitochondrial proteins during early embryonic development in Caenorhabditis elegans vol.294, pp.9, 2013, https://doi.org/10.1074/jbc.ra118.004726
  45. Maize polyamine oxidase in the presence of spermine/spermidine induces the apoptosis of LoVo human colon adenocarcinoma cells vol.54, pp.6, 2013, https://doi.org/10.3892/ijo.2019.4780
  46. Detection of biogenic polyamines in blood of patients with breast cancer vol.10, pp.2, 2013, https://doi.org/10.15421/021939
  47. Salivary metabolomics with alternative decision tree-based machine learning methods for breast cancer discrimination vol.177, pp.3, 2019, https://doi.org/10.1007/s10549-019-05330-9
  48. The potential therapeutic effect of NG-hydroxy-nor-L-arginine in 7,12-dimethylbenz(a)anthracene-induced breast cancer in rats vol.111, pp.None, 2013, https://doi.org/10.1016/j.yexmp.2019.104316
  49. Gender-Related Differences on Polyamine Metabolome in Liquid Biopsies by a Simple and Sensitive Two-Step Liquid-Liquid Extraction and LC-MS/MS vol.9, pp.12, 2013, https://doi.org/10.3390/biom9120779
  50. Aggregation Induced Emission Switching Based Ultrasensitive Ratiometric Detection of Biogenic Diamines Using a Perylenediimide-Based Smart Fluoroprobe vol.11, pp.50, 2013, https://doi.org/10.1021/acsami.9b14690
  51. Density functional calculations on the structural and vibrational properties of 1,4-diaminobutane vol.1199, pp.None, 2013, https://doi.org/10.1016/j.molstruc.2019.126974
  52. Skyline for Small Molecules: A Unifying Software Package for Quantitative Metabolomics vol.19, pp.4, 2013, https://doi.org/10.1021/acs.jproteome.9b00640
  53. Response of the Intertidal Microbial Community Structure and Metabolic Profiles to Zinc Oxide Nanoparticle Exposure vol.17, pp.7, 2013, https://doi.org/10.3390/ijerph17072253
  54. Triggering doxorubicin release from responsive hydrogel films by polyamine uptake vol.16, pp.32, 2013, https://doi.org/10.1039/d0sm00951b
  55. Nutritional Aspects of Spermidine vol.40, pp.1, 2013, https://doi.org/10.1146/annurev-nutr-120419-015419
  56. IL-12p40/IL-23p40 Blockade With Ustekinumab Decreases the Synovial Inflammatory Infiltrate Through Modulation of Multiple Signaling Pathways Including MAPK-ERK and Wnt vol.12, pp.None, 2013, https://doi.org/10.3389/fimmu.2021.611656
  57. Polyamine biomarkers as indicators of human disease vol.26, pp.2, 2021, https://doi.org/10.1080/1354750x.2021.1875506
  58. Aberrant AZIN2 and polyamine metabolism precipitates tau neuropathology vol.131, pp.4, 2013, https://doi.org/10.1172/jci126299
  59. Polyamine Homeostasis in Development and Disease vol.9, pp.2, 2013, https://doi.org/10.3390/medsci9020028
  60. Adipose-Derived Stem Cell Features and MCF-7 vol.10, pp.7, 2021, https://doi.org/10.3390/cells10071754
  61. The Polyamine Regulator AMD1 Upregulates Spermine Levels to Drive Epidermal Differentiation vol.141, pp.9, 2021, https://doi.org/10.1016/j.jid.2021.01.039
  62. Benzothiazole derivatives based colorimetric and fluorescent probes for detection of amine/ammonia and monitoring the decomposition of urea by urease vol.267, pp.p2, 2013, https://doi.org/10.1016/j.saa.2021.120616