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Leena Alhonen


Ph.D. in Biochemistry, Department of Biochemistry, University of Helsinki, Finland, 1981

Current position

Professor, School of Pharmacy, University of Eastern Finland, Kuopio Campus, Finland

Publications (since 2010)

  1. Weisell, J., Hyvonen, M. T., Alhonen, L., Vepsalainen, J., Keinanen, T. A. and Khomutov, A. R. (2014). Charge deficient analogues of the natural polyamines. Curr Pharm Des 20(2): 262-277.
  2. Pietila, M., Dhungana, H., Uimari, A., Sironen, R. and Alhonen, L. (2014). Systemic overexpression of antizyme 1 in mouse reduces ornithine decarboxylase activity without major changes in tissue polyamine homeostasis. Transgenic Res 23(1): 153-163.
  3. Keinanen, T. A., Hyvonen, M. T., Alhonen, L., Vepsalainen, J. and Khomutov, A. R. (2014). Selective regulation of polyamine metabolism with methylated polyamine analogues. Amino Acids 46(3): 605-620.
  4. Keinanen, T., Hyvonen, T., Vepsalainen, J., Alhonen, L., Khomutov, A. and Janne, J. (2014). Stable analogues of coenzyme-substrate complex of spermidine/spermine-N 1-acetyltransferase reaction. Synthesis and interaction with the enzyme. Russian Journal of Bioorganic Chemistry 40(2): 155-161.
  5. Pirnes-Karhu, S., Mantymaa, P., Sironen, R., Makinen, P. I., Wojciechowski, S., Juutinen, S., Koistinaho, J., Horkko, S., Jantunen, E., Alhonen, L. and Uimari, A. (2014). Enhanced polyamine catabolism disturbs hematopoietic lineage commitment and leads to a myeloproliferative disease in mice overexpressing spermidine/spermine N(1)-acetyltransferase. Amino Acids 46(3): 689-700.
  6. Haghighi Poodeh, S., Alhonen, L., Salonurmi, T. and Savolainen, M. J. (2014). Ethanol-induced impairment of polyamine homeostasis--a potential cause of neural tube defect and intrauterine growth restriction in fetal alcohol syndrome. Biochem Biophys Res Commun 446(1): 173-178.
  7. Kraus, D., Yang, Q., Kong, D., Banks, A. S., Zhang, L., Rodgers, J. T., Pirinen, E., Pulinilkunnil, T. C., Gong, F., Wang, Y. C., Cen, Y., Sauve, A. A., Asara, J. M., Peroni, O. D., Monia, B. P., Bhanot, S., Alhonen, L., Puigserver, P. and Kahn, B. B. (2014). Nicotinamide N-methyltransferase knockdown protects against diet-induced obesity. Nature 508(7495): 258-262.
  8. Pirnes-Karhu, S., Jantunen, E., Mantymaa, P., Mustjoki, S., Alhonen, L. and Uimari, A. (2014). Spermidine/spermine N(1)-acetyltransferase activity associates with white blood cell count in myeloid leukemias. Exp Hematol 42(7): 574-580.
  9. Vapola, M. H., Rokka, A., Sormunen, R. T., Alhonen, L., Schmitz, W., Conzelmann, E., Warri, A., Grunau, S., Antonenkov, V. D. and Hiltunen, J. K. (2014). Peroxisomal membrane channel Pxmp2 in the mammary fat pad is essential for stromal lipid homeostasis and for development of mammary gland epithelium in mice. Dev Biol 391(1): 66-80.
  10. Pirnes-Karhu, S., Maatta, J., Finnila, M., Alhonen, L. and Uimari, A. (2014). Overexpression of spermidine/spermine N 1-acetyltransferase impairs osteoblastogenesis and alters mouse bone phenotype. Transgenic Res. (Epub ahead of print)
  11. Hyvonen, M. T., Weisell, J., Khomutov, A. R., Alhonen, L., Vepsalainen, J. and Keinanen, T. A. (2013). Metabolism of triethylenetetramine and 1,12-diamino-3,6,9-triazadodecane by the spermidine/spermine-N(1)-acetyltransferase and thialysine acetyltransferase. Drug Metab Dispos 41(1): 30-32.
  12. Hyvonen, M. T., Koponen, T., Weisell, J., Pietila, M., Khomutov, A. R., Vepsalainen, J., Alhonen, L. and Keinanen, T. A. (2013). Spermidine promotes adipogenesis of 3T3-L1 cells by preventing interaction of ANP32 with HuR and PP2A. Biochem J 453(3): 467-474.
  13. Khomutov, M. A., Weisell, J., Hyvonen, M., Keinanen, T. A., Vepsalainen, J., Alhonen, L., Khomutov, A. R. and Kochetkov, S. N. (2013). Hydroxylamine derivatives for regulation of spermine and spermidine metabolism. Biochemistry (Mosc) 78(13): 1431-1446.
  14. Koponen, T., Cerrada-Gimenez, M., Pirinen, E., Hohtola, E., Paananen, J., Vuohelainen, S., Tusa, M., Pirnes-Karhu, S., Heikkinen, S. and Virkamäki, A. (2012). The activation of hepatic and muscle polyamine catabolism improves glucose homeostasis. Amino acids 42(2-3): 427-440.
  15. Cerrada-Gimenez, M., Häkkinen, M. R., Vepsäläinen, J., Auriola, S., Alhonen, L. and Keinänen, T. A. (2012). Polyamine flux analysis by determination of heavy isotope incorporation from 13C, 15N-enriched amino acids into polyamines by LC–MS/MS. Amino Acids 42(2-3): 451-460.
  16. Uimari, A., Merentie, M., Sironen, R., Pirnes-Karhu, S., Peraniemi, S. and Alhonen, L. (2012). Overexpression of spermidine/spermine N1-acetyltransferase or treatment with N1-N11-diethylnorspermine attenuates the severity of zinc-induced pancreatitis in mouse. Amino Acids 42(2-3): 461-471.
  17. Pirnes-Karhu, S., Sironen, R., Alhonen, L. and Uimari, A. (2012). Lipopolysaccharide-induced anti-inflammatory acute phase response is enhanced in spermidine/spermine N1-acetyltransferase (SSAT) overexpressing mice. Amino Acids 42(2-3): 473-484.
  18. Hyvonen, M. T., Uimari, A., Vepsalainen, J., Khomutov, A. R., Keinanen, T. A. and Alhonen, L. (2012). Tissue-specific alternative splicing of spermidine/spermine N1-acetyltransferase. Amino Acids 42(2-3): 485-493.
  19. Pietila, M., Lampinen, A., Pellinen, R. and Alhonen, L. (2012). Inducible expression of antizyme 1 in prostate cancer cell lines after lentivirus mediated gene transfer. Amino Acids 42(2-3): 559-564.
  20. Hyvonen, M. T., Keinanen, T. A., Khomutov, M., Simonian, A., Vepsalainen, J., Park, J. H., Khomutov, A. R., Alhonen, L. and Park, M. H. (2012). Effects of novel C-methylated spermidine analogs on cell growth via hypusination of eukaryotic translation initiation factor 5A. Amino Acids 42(2-3): 685-695.
  21. Nayvelt, I., John, S., Hsu, H. C., Yang, P., Liu, W., Das, G., Hyvonen, M. T., Alhonen, L., Keinanen, T. A., Shirahata, A., Patel, R., Thomas, T. and Thomas, T. J. (2012). A potential estrogen mimetic effect of a bis(ethyl)polyamine analogue on estrogen receptor positive MCF-7 breast cancer cells. Amino Acids 42(2-3): 899-911.
  22. Cerrada-Gimenez, M., Tusa, M., Casellas, A., Pirinen, E., Moya, M., Bosch, F. and Alhonen, L. (2012). Altered glucose-stimulated insulin secretion in a mouse line with activated polyamine catabolism. Transgenic Res 21(4): 843-853.
  23. Van den Bossche, J., Lamers, W. H., Koehler, E. S., Geuns, J. M., Alhonen, L., Uimari, A., Pirnes-Karhu, S., Van Overmeire, E., Morias, Y., Brys, L., Vereecke, L., De Baetselier, P. and Van Ginderachter, J. A. (2012). Pivotal Advance: Arginase-1-independent polyamine production stimulates the expression of IL-4-induced alternatively activated macrophage markers while inhibiting LPS-induced expression of inflammatory genes. J Leukoc Biol 91(5): 685-699.
  24. Smirnova, O. A., Isaguliants, M. G., Hyvonen, M. T., Keinanen, T. A., Tunitskaya, V. L., Vepsalainen, J., Alhonen, L., Kochetkov, S. N. and Ivanov, A. V. (2012). Chemically induced oxidative stress increases polyamine levels by activating the transcription of ornithine decarboxylase and spermidine/spermine-N1-acetyltransferase in human hepatoma HUH7 cells. Biochimie 94(9): 1876-1883.
  25. 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(2): 387-396.
  26. Uimari, A., Hyvonen, M. T., Pirinen, E. and Alhonen, L. (2011). Transgenic rodents with altered SSAT expression as models of pancreatitis and altered glucose and lipid metabolism. Methods Mol Biol 720: 143-158.
  27. Khomutov, A. R., Weisell, J., Khomutov, M. A., Grigorenko, N. A., Simonian, A. R., Hakkinen, M. R., Keinanen, T. A., Hyvonen, M. T., Alhonen, L., Kochetkov, S. N. and Vepsalainen, J. (2011). Methylated polyamines as research tools. Methods Mol Biol 720: 449-461.
  28. Khomutov, M. A., Khivonen, M. T., Simonian, A. R., Vepsalainen, I., Alkhonen, L., Kochetkov, S. N. and Keinanen, T. A. (2011). Novel metabolically stable functionally-active mimetic of spermidine. Bioorg Khim 37(2): 253-258.
  29. Jin, H. T., Lamsa, T., Nordback, P. H., Hyvonen, M. T., Raty, S., Nordback, I., Herzig, K. H., Alhonen, L. and Sand, J. (2011). Polyamine catabolism in relation to trypsin activation and apoptosis in experimental acute pancreatitis. Pancreatology 11(2): 83-91.
  30. Hyvonen, M. T., Keinanen, T. A., Khomutov, M., Simonian, A., Weisell, J., Kochetkov, S. N., Vepsalainen, J., Alhonen, L. and Khomutov, A. R. (2011). The use of novel C-methylated spermidine derivatives to investigate the regulation of polyamine metabolism. J Med Chem 54(13): 4611-4618.
  31. Jin, H. T., Lamsa, T., Nordback, P. H., Hyvonen, M. T., Grigorenko, N., Khomutov, A. R., Nordback, I., Raty, S., Porsti, I., Alhonen, L. and Sand, J. (2011). Association between remote organ injury and tissue polyamine homeostasis in acute experimental pancreatitis - treatment with a polyamine analogue bismethylspermine. Pharmacol Rep 63(4): 999-1008.
  32. Biczo, G., Hegyi, P., Dosa, S., Shalbuyeva, N., Berczi, S., Sinervirta, R., Hracsko, Z., Siska, A., Kukor, Z., Jarmay, K., Venglovecz, V., Varga, I. S., Ivanyi, B., Alhonen, L., Wittmann, T., Gukovskaya, A., Takacs, T. and Rakonczay, Z., Jr. (2011). The crucial role of early mitochondrial injury in L-lysine-induced acute pancreatitis. Antioxid Redox Signal 15(10): 2669-2681.
  33. Cerrada-Gimenez, M., Weisell, J., Hyvonen, M. T., Park, M. H., Alhonen, L., Vepsalainen, J. and Keinanen, T. A. (2011). Complex N-acetylation of triethylenetetramine. Drug Metab Dispos 39(12): 2242-2249.
  34. Nayvelt, I., Hyvonen, M. T., Alhonen, L., Pandya, I., Thomas, T., Khomutov, A. R., Vepsalainen, J., Patel, R., Keinanen, T. A. and Thomas, T. J. (2010). DNA condensation by chiral alpha-methylated polyamine analogues and protection of cellular DNA from oxidative damage. Biomacromolecules 11(1): 97-105.
  35. Makela, K. A., Wigren, H. K., Zant, J. C., Sakurai, T., Alhonen, L., Kostin, A., Porkka-Heiskanen, T. and Herzig, K. H. (2010). Characterization of sleep-wake patterns in a novel transgenic mouse line overexpressing human prepro-orexin/hypocretin. Acta Physiol (Oxf) 198(3): 237-249.
  36. Hakkinen, M. R., Hyvonen, M. T., Auriola, S., Casero, R. A., Jr., Vepsalainen, J., Khomutov, A. R., Alhonen, L. and Keinanen, T. A. (2010). Metabolism of N-alkylated spermine analogues by polyamine and spermine oxidases. Amino Acids 38(2): 369-381.
  37. Weisell, J., Hyvonen, M. T., Vepsalainen, J., Alhonen, L., Keinanen, T. A., Khomutov, A. R. and Soininen, P. (2010). Novel isosteric charge-deficient spermine analogue--1,12-diamino-3,6,9-triazadodecane: synthesis, pK(a) measurement and biological activity. Amino Acids 38(2): 501-507.
  38. Pirinen, E., Gylling, H., Itkonen, P., Yaluri, N., Heikkinen, S., Pietila, M., Kuulasmaa, T., Tusa, M., Cerrada-Gimenez, M., Pihlajamaki, J., Alhonen, L., Janne, J., Miettinen, T. A. and Laakso, M. (2010). Activated polyamine catabolism leads to low cholesterol levels by enhancing bile acid synthesis. Amino Acids 38(2): 549-560.
  39. Hyvonen, M. T., Sinervirta, R., Grigorenko, N., Khomutov, A. R., Vepsalainen, J., Keinanen, T. A. and Alhonen, L. (2010). alpha-Methylspermidine protects against carbon tetrachloride-induced hepatic and pancreatic damage. Amino Acids 38(2): 575-581.
  40. Fashe, T. M., Keinanen, T. A., Grigorenko, N. A., Khomutov, A. R., Janne, J., Alhonen, L. and Pietila, M. (2010). Cutaneous application of alpha-methylspermidine activates the growth of resting hair follicles in mice. Amino Acids 38(2): 583-590.
  41. Cerrada-Gimenez, M., Hayrinen, J., Juutinen, S., Reponen, T., Janne, J. and Alhonen, L. (2010). Proteomic analysis of livers from a transgenic mouse line with activated polyamine catabolism. Amino Acids 38(2): 613-622.
  42. Leon, W. C., Canneva, F., Partridge, V., Allard, S., Ferretti, M. T., DeWilde, A., Vercauteren, F., Atifeh, R., Ducatenzeiler, A., Klein, W., Szyf, M., Alhonen, L. and Cuello, A. C. (2010). A novel transgenic rat model with a full Alzheimer's-like amyloid pathology displays pre-plaque intracellular amyloid-beta-associated cognitive impairment. J Alzheimers Dis 20(1): 113-126.
  43. Hyvonen, M. T., Sinervirta, R., Keinanen, T. A., Fashe, T., Grigorenko, N., Khomutov, A. R., Vepsalainen, J. and Alhonen, L. (2010). Acute pancreatitis induced by activated polyamine catabolism is associated with coagulopathy: effects of alpha-methylated polyamine analogs on hemostasis. Pancreatology 10(2-3): 208-221.
  44. Zahedi, K., Barone, S., Kramer, D. L., Amlal, H., Alhonen, L., Janne, J., Porter, C. W. and Soleimani, M. (2010). The role of spermidine/spermine N1-acetyltransferase in endotoxin-induced acute kidney injury. Am J Physiol Cell Physiol 299(1): C164-174.
  45. Vuohelainen, S., Pirinen, E., Cerrada-Gimenez, M., Keinanen, T. A., Uimari, A., Pietila, M., Khomutov, A. R., Janne, J. and Alhonen, L. (2010). Spermidine is indispensable in differentiation of 3T3-L1 fibroblasts to adipocytes. J Cell Mol Med 14(6B): 1683-1692.
  46. Ramot, Y., Pietila, M., Giuliani, G., Rinaldi, F., Alhonen, L. and Paus, R. (2010). Polyamines and hair: a couple in search of perfection. Exp Dermatol 19(9): 784-790.
  47. Weisell, J., Hyvonen, M. T., Hakkinen, M. R., Grigorenko, N. A., Pietila, M., Lampinen, A., Kochetkov, S. N., Alhonen, L., Vepsalainen, J., Keinanen, T. A. and Khomutov, A. R. (2010). Synthesis and biological characterization of novel charge-deficient spermine analogues. J Med Chem 53(15): 5738-5748.
  48. Biczo, G., Hegyi, P., Sinervirta, R., Berczi, S., Dosa, S., Siska, A., Ivanyi, B., Venglovecz, V., Takacs, T., Alhonen, L. and Rakonczay, Z., Jr. (2010). Characterization of polyamine homeostasis in l-ornithine-induced acute pancreatitis in rats. Pancreas 39(7): 1047-1056.
  49. Bry, M., Kivela, R., Holopainen, T., Anisimov, A., Tammela, T., Soronen, J., Silvola, J., Saraste, A., Jeltsch, M., Korpisalo, P., Carmeliet, P., Lemstrom, K. B., Shibuya, M., Yla-Herttuala, S., Alhonen, L., Mervaala, E., Andersson, L. C., Knuuti, J. and Alitalo, K. (2010). Vascular endothelial growth factor-B acts as a coronary growth factor in transgenic rats without inducing angiogenesis, vascular leak, or inflammation. Circulation 122(17): 1725-1733.
Protocols by Leena Alhonen
  1. Assay of Ornithine Decarboxylase and Spermidine/Spermine N1-acetyltransferase Activities