Skip to main content

Advertisement

Log in

Metabolic correlations of glucocorticoids and polyamines in inflammation and apoptosis

  • Invited Review
  • Published:
Amino Acids Aims and scope Submit manuscript

Abstract

Glucocorticoid hormones (GC) are essential in all aspects of human health and disease. Their anti-inflammatory and immunosuppressive properties are reasons for therapeutic application in several diseases. GC suppress immune activation and uncontrolled overproduction and release of cytokines. GC inhibit the release of pro-inflammatory cytokines and stimulate the production of anti-inflammatory cytokines. Investigation of GC’s mechanism of action, suggested that polyamines (PA) may act as mediators or messengers of their effects. Beside glucocorticoids, spermine (Spm) is one of endogenous inhibitors of cytokine production. There are many similarities in the metabolic actions of GC and PA. The major mechanism of GC effects involves the regulation of gene expression. PA are essential for maintaining higher order organization of chromatin in vivo. Spermidine and Spm stabilize chromatin and nuclear enzymes, due to their ability to form complexes with negatively charged groups on DNA, RNA and proteins. Also, there is an increasing body of evidence that GC and PA change the chromatin structure especially through acetylation and deacetylation of histones. GC display potent immunomodulatory activities, including the ability to induce T and B lymphocyte apoptosis, mediated via production of reactive oxygen species (ROS) in the mitochondrial pathway. The by-products of PA catabolic pathways (hydrogen peroxide, amino aldehydes, acrolein) produce ROS, well-known cytotoxic agents involved in programmed cell death (PCD) or apoptosis. This review is an attempt in the better understanding of relation between GC and PA, naturally occurring compounds of all eukaryotic cells, anti-inflammatory and apoptotic agents in physiological and pathological conditions connected to oxidative stress or PCD.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  • Abbott AC, Bird CC (1983) Cytolethal sensitivity of human lymphoid cells to glucocorticoids and oxidized polyamines. Biochem Biophys Res Commun 115:737–742

    Article  CAS  PubMed  Google Scholar 

  • Auphan N, Di Donato JA, Rosette C, Helmberg A, Karin M (1995) Immunosuppression by glucocorticoids: inhibition of NF-κB activity through induction of IκB synthesis. Science 270:286–290

    Article  CAS  PubMed  Google Scholar 

  • Babbar N, Gerner EW, Casero RA (2006a) Induction of spermidine/spermine N1-acetyltransferase (SSAT) by aspirin in Caco-2 colon cancer cells. Biochem J 394:317–324

    Article  CAS  PubMed  Google Scholar 

  • Babbar N, Amy Hacker A, Huang Y, Casero RA (2006b) Tumor necrosis factor α induces spermidine/spermine N1-acetyltransferase through nuclear factor κB in non-small cell lung cancer cells. J Biol Chem 281(34):24182–24192

    Article  CAS  PubMed  Google Scholar 

  • Babbar N, Murray-Stewart T, Casero RA (2007) Inflammation and polyamine catabolism: the good, the bad and the ugly. Biochem Soc Trans 35:300–304

    Article  CAS  PubMed  Google Scholar 

  • Bachrach U (2004) Polyamines and cancer. Amino Acids 26:307–309

    Article  CAS  PubMed  Google Scholar 

  • Baldwin AS (1996) The NF-κB and IκB proteins: new discoveries and insights. Annu Rev Immunol 14:649–683

    Article  CAS  PubMed  Google Scholar 

  • Barnes PJ (1998) Editorial review: anti-inflammatory actions of glucocorticoids: molecular mechanisms. Clin Sci 94:557–572

    CAS  PubMed  Google Scholar 

  • Barnes PJ (2006) Corticosteroids: the drugs to beat. Eur J Pharmacol 533(1–3):2–14

    Article  CAS  PubMed  Google Scholar 

  • Barnes PJ, Adcock IM (1993) Anti-inflammatory actions of steroids: molecular mechanisms. Trends Pharmacol Sci 14:436–441

    Article  CAS  PubMed  Google Scholar 

  • Bauer PM, Fukuto JM, Buga GM, Pegg AE, Ignarro LJ (1999) Nitric oxide inhibits ornithine decarboxylase by S-nitrosylation. Biochem Biophys Res Commun 262:355–358

    Article  CAS  PubMed  Google Scholar 

  • Bauer PM, Buga GM, Fukuto JM, Pegg AE, Louis J, Ignarro LJ (2001) Nitric oxide inhibits ornithine decarboxylase via S-nitrosylation of cysteine 360 in the active site of the enzyme. J Biol Chem 276(37):34458–34464

    Article  CAS  PubMed  Google Scholar 

  • Baxter JD, Rousseau GG (1979) Glucocorticoid hormone action. Monogr Endocrinol 12:1–24

    CAS  PubMed  Google Scholar 

  • Beaven MA. Intracellular signaling section. http://www.dir.nhlbi.nih.gov/labs/lmi/ics/

  • Bernardi P, Scorrano L, Colonna R, Petronilli V, Di Lisa F (1999) Mitochondria and cell death. Mechanistic aspects and methodological issues. Eur J Biochem 264:687–701

    Article  CAS  PubMed  Google Scholar 

  • Bishop BP, Young J, Peng T, Richards JF (1985) An inhibitor of ornithine decarboxylase in thymus and spleen of dexamethasone-treated rats. Biochem J 226:105–112

    CAS  PubMed  Google Scholar 

  • Bjelakovic G, Pavlovic D (1987) Effect of pyridoxine on the polyamine oxidase activity in the liver and spleen of dexamethasone-treated guinea-pigs. Yugosl Physiol Pharmacol Acta 24:249–256 (Serbian)

    Google Scholar 

  • Bjelakovic G, Pavlovic D, Stojanovic I, Jevtovic T, Nikolic J, Kocic G (2006) Effects of glucocorticoids on polyamine metabolism in liver and spleen of guinea pig during sensitization. Amino Acids 31:457–462

    Article  CAS  PubMed  Google Scholar 

  • Bonneau MJ, Poulin R (2000) Spermine oxidation leads to necrosis with plasma membrane phosphatidylserine redistribution in mouse leukemia cells. Exp Cell Res 259(1):23–34

    Article  CAS  PubMed  Google Scholar 

  • Boumpas DT (1972) A novel action of glucocorticoids—NF kappaB inhibition. Br J Rheumatol 35(8):709–710

    Article  Google Scholar 

  • Boumpas DT, Chrousos GP, Wilder RL, Cupps TR, Balow JE (1993) Glucocorticoid therapy for immune-mediated diseases: basic and clinical correlates. Ann Intern Med 119(12):1198–1208

    CAS  PubMed  Google Scholar 

  • Brune B, Hartzell P, Nicotera P, Orrenius S (1991) Spermine prevents endonuclease activation and apoptosis in thymocytes. Exp Cell Res 195:323–329

    Article  CAS  PubMed  Google Scholar 

  • Bursch W, Ellinger A, Gerner CH, Frohwein U, Schulte-Hermann R (2000) Programmed cell death (PCD): apoptosis, autophagic PCD, or others? An NY Acad Sci 926:1–12

    Article  CAS  Google Scholar 

  • Choi W, Proctor L, Xia Q, Feng Y, Gerner EW, Chiao PJ, Hamilton SR, Zhang W (2006) Inactivation of IkappaB contributes to transcriptional activation of spermidine/spermine N(1)-acetyltransferase. Mol Carcinog 45(9):685–693

    Article  CAS  PubMed  Google Scholar 

  • Chrousos PG (1995) The hypothalamic–pituitary–adrenal axis and immune-mediated inflammation. N Engl J Med 332(20):1351–1363

    Article  CAS  PubMed  Google Scholar 

  • Cifone MG, Migliorati G, Parroni R, Marchetti C, Millimaggi D, Santoni A, Riccardi C (1999) Dexamethasone-induced thymocyte apoptosis: apoptotic signal involves the sequential activation of phosphoinositide-specific phospholipase C, acidic sphingomyelinase, and caspases. Blood 93(7):2282–2296

    CAS  PubMed  Google Scholar 

  • Cohen JJ (1993) Programmed cell death and apoptosis in lymphocyte development and function. Chest 103(2 Suppl):99S–101S

    Article  CAS  PubMed  Google Scholar 

  • Cohen SS (1998) A guide to the polyamines. 1-543 Oxford University Press, New York

  • Colombatto S, Fasulo L, Grillo MA (1988) Polyamines in rat liver during experimental inflammation. Agents Actions 24(3–4):326–330

    Article  CAS  PubMed  Google Scholar 

  • Cosío BG, Torrego A, Adcock IM (2005) Molecular mechanisms of glucocorticoids. Arch Bronchoneumol 41:34–41

    Google Scholar 

  • D’Agostino L, Di Luccia A (2002) Polyamines interact with DNA as molecular aggregates. Eur J Biochem 269:4317–4325

    Article  PubMed  CAS  Google Scholar 

  • Dalla Via L, Di Noto V, Toninello A (1999) Binding of spermidine and putrescine to energized liver mitochondria. Arch Biochem Biophys 365(2):231–238

    Article  CAS  PubMed  Google Scholar 

  • Dash P (2005) Apoptosis. Basic Medical Sciences, St George’s, University of London (http://www.sgul.ac.uk/depts/immunology/~dash)

  • Dash PR, Cartwright JE, GStJ Whitley (2003) Nitric oxide inhibits polyamine-induced apoptosis in the human extravillous trophoblast cell line SGHPL-4. Hum Reprod 18(5):959–968

    Article  CAS  PubMed  Google Scholar 

  • Datta RK, Sen S, Ghosh JJ (1969) Effect of polyamines on the stability of brain-cortex ribosomes. Biochem J 114:847–854

    CAS  PubMed  Google Scholar 

  • De Bosscher K, Vanden Berghe W, Haegeman G (2003) The interplay between the glucocorticoid receptor and nuclear factor κB or activator protein-1: molecular mechanisms for gene repression. Endocr Rev 24(4):488–522

    Article  PubMed  CAS  Google Scholar 

  • Demonacos C, Djordjevic-Markovic R, Tsawdaroglou N, Sekeris CE (1995) The mitochondrion as a primary site of action of glucocorticoids: the interaction of the glucocorticoid receptor with mitochondrial DNA sequences showing partial similarity to the nuclear glucocorticoid responsive elements. J Steroid Biochem Mol Biol 55(1):43–55

    Article  CAS  PubMed  Google Scholar 

  • Deng W, Viar MJ, Johnson LR (2005) Polyamine depletion inhibits irradiation-induced apoptosis in intestinal epithelia. Am J Physiol Gastrointest Liver Physiol 289:G599–G606

    Article  CAS  PubMed  Google Scholar 

  • Deroo BJ, Archer TK (2001a) Glucocorticoid receptor activation of the IκBα promoter within chromatin. Mol Biol Cell 12(11):3365–3374

    CAS  PubMed  Google Scholar 

  • Deroo BJ, Archer TK (2001b) Glucocorticoid receptor-mediated chromatin remodeling in vivo. Oncogene 20:3039–3046

    Article  CAS  PubMed  Google Scholar 

  • Desiderio MA, Stefano Mattei S, Biondi G, Colombo MP (1993) Cytosolic and nuclear spermidine acetyltransferases in growing NIH 3T3 fibroblasts stimulated with serum or polyamines: relationship to polyamine-biosynthetic decarboxylases and histone acetyltransferase. Biochem J 293:475–479

    CAS  PubMed  Google Scholar 

  • Desiderio MA, Grassilli E, Bellesia E, Salomoni P, Franceschi C (1995) Involvement of ornithine decarboxylase and polyamines in glucocorticoid-induced apoptosis of rat thymocytes. Cell Growth Differ 6:505–513

    CAS  PubMed  Google Scholar 

  • Desiderio MA, Pogliaghi G, Dansi P (1998) Regulation of spermidine/spermine N1-acetyltransferase expression by cytokines and polyamines in human hepatocarcinoma cells (HepG2). J Cell Physiol 174:125–134

    Article  CAS  PubMed  Google Scholar 

  • Díaz-Guerra MJM, Velasco M, Martin-Sanz P, Bosca L (1997) Nuclear factor κB is required for the transcriptional control of type II NO synthase in regenerating liver. Biochem J 326:791–797

    PubMed  Google Scholar 

  • Distelhorst CW (2002) Recent insights into the mechanism of glucocorticosteroid induced apoptosis. Cell Death Differ 9:6–19

    Article  CAS  PubMed  Google Scholar 

  • Duma D, Jewell CM, Cidlowski AJ (2006) Multiple glucocorticoid receptor isoforms and mechanisms of post-translational modification. J Steroid Biochem Mol Biol 102(1–5):11–21

    Article  CAS  PubMed  Google Scholar 

  • Elenkov IJ, Chrousos GP (2002) Stress hormones, proinflammatory and anti-inflammatory cytokines, and autoimmunity. Ann NY Acad Sci 966:290–303

    Article  CAS  PubMed  Google Scholar 

  • Erez O, Goldstaub D, Friedman J, Kahana C (2002) Putrescine activates oxidative stress dependent apoptotic death in ornithine decarboxylase overproducing mouse myeloma cells. Exp Cell Res 281:148–156

    Article  CAS  PubMed  Google Scholar 

  • Fadeel B, Orrenius S, Zhivotovsky B (1999) Apoptosis in human disease: a new skin for the old ceremony? Biochem Biophys Res Commun 266:699–717

    Article  CAS  PubMed  Google Scholar 

  • Ferioli EM, Pinottia O, Pironaa L (1999) Polyamine oxidase activity in lymphoid tissues of glucocorticoid-treated rats. Biochem Pharmacol 58(12):1907–1914

    Article  CAS  PubMed  Google Scholar 

  • Ferioli ME, Pirona L, Pinotti O (2000) Prolactin and polyamine catabolism: specific effect on polyamine oxidase activity in rat thymus. Mol Cell Endocrinol 165(1–2):51–56

    Article  CAS  PubMed  Google Scholar 

  • Ferrante A (1985) Inhibition of human neutrophil locomotion by the polyamine oxidase–polyamine system. Immunology 54:785–790

    CAS  PubMed  Google Scholar 

  • Franchimont D (2004) Overview of the actions of glucocorticoids on the immune response: a good model to characterize new pathways of immunosuppression for new treatment strategies. Ann NY Acad Sci 1024:124–137

    Article  CAS  PubMed  Google Scholar 

  • Fraser AV, Woster PM, Wallace HM (2002) Induction of apoptosis in human leukemic cells by IPENSpermine, a novel polyamine analogue and anti-metabolite. Biochem J 367:307–312

    Article  CAS  PubMed  Google Scholar 

  • Goulding NJ (2004) The molecular complexity of glucocorticoid actions in inflammation—a four-ring circus. Curr Opin Pharmacol 4(6):629–636

    Article  CAS  PubMed  Google Scholar 

  • Green DR, Reed JC (1998) Mitochondria and apoptosis. Science 281:1309–1312

    Article  CAS  PubMed  Google Scholar 

  • Ha HC, Sirisoma SN, Kuppusamy P, Zweier JL, Patrick M, Woster PM, Casero RA (1998) The natural polyamine spermine functions directly as a free radical scavenger. Proc Natl Acad Sci USA 95(19):11140–11145

    Article  CAS  PubMed  Google Scholar 

  • Heby O (1981) Role of polyamines in the control cell proliferation and differentiation. Differentiation 19:1–20

    Article  CAS  PubMed  Google Scholar 

  • Heby O, Persson L (1990) Molecular genetics of polyamine synthesis in eukaryotic cells. Trends Biochem Sci 15:152–158

    Article  Google Scholar 

  • Hegardt C (2000) On the role of polyamines in apoptosis Avhandling. Dissertation, Lund University

  • Hegardt C, Andersson G, Oredson SM (2000) Changes in polyamine metabolism during glucocorticoid-induced programmed cell death in mouse thymus. Cell Biol Int 24(12):871–880

    Article  CAS  PubMed  Google Scholar 

  • Hegardt C, Andersson G, Oredsson SM (2001) Different roles of spermine in glucocorticoid- and Fas-induced apoptosis. Exp Cell Res 266(2):333–341

    Article  CAS  PubMed  Google Scholar 

  • Hegardt C, Andersson G, Oredsson SM (2003) Spermine prevents cytochrome c release in glucocorticoid-induced apoptosis in mouse thymocytes. Cell Biol Int 27(2):115–121

    Article  CAS  PubMed  Google Scholar 

  • Herold JMJ, McPherson KG, Reichardt HM (2006) Glucocorticoids in T cell apoptosis and function. Cell Mol Life Sci 63:60–72

    Article  CAS  PubMed  Google Scholar 

  • Hirsch JG, Dubos RJ (1952) The effect of spermine on tubercle bacilli. J Exp Med 95:191–208

    Article  CAS  PubMed  Google Scholar 

  • Hobbs CA, Gilmour SK (2000) High levels of intracellular polyamines promote histone acetyltransferase activity resulting in chromatin hyperacetylation. J Cell Biochem 77:345–360

    Article  CAS  PubMed  Google Scholar 

  • Hogg N, Kalyanaraman B, Joseph J, Struck A, Parthasarathy S (1993) Inhibition of low density lipoprotein oxidation by nitric oxide. Potential role in atherogenesis. FEBS Lett 334:170–174

    Article  CAS  PubMed  Google Scholar 

  • Hölttä E (1977) Oxidation of spermidine and spermine in rat liver: purification and properties of polyamine oxidase. Biochemistry 16:91–100

    Article  PubMed  Google Scholar 

  • Hoshino K, Momiyama E, Yoshida K, Nishimura K, Sakai S, Toida T, Kashiwagi K, Igarashi K (2005) Polyamine transport by mammalian cells and mitochondria: role of antizyme and glycosaminoglycans. J Biol Chem 280(52):42801–42808

    Article  CAS  PubMed  Google Scholar 

  • Ientile R, De Luca G, Di Giorgio MR, Macaione S (1988) Glucocorticoid regulation of spermidine acetylation in the rat brain. J Neurochem 51(3):677–682

    Article  CAS  PubMed  Google Scholar 

  • Igarashi K, Kashiwagi K (2000) Polyamines: mysterious modulators of cellular functions. Biochem Biophys Res Commun 271(3):559–564

    Article  CAS  PubMed  Google Scholar 

  • Igarashi K, Kashiwagi K (2006) Polyamine modulation in Escherichia coli: genes involved in the stimulation of cell growth by polyamines. J Biochem 139(1):11–16

    Article  CAS  PubMed  Google Scholar 

  • Iuchi T, Akaike M, Mitsui T, Ohshima Y, Shintani Y, Azuma H, Matsumoto T (2003) Glucocorticoid excess induces superoxide production in vascular endothelial cells and elicits vascular endothelial. Circ Res 92:81–89

    Article  CAS  PubMed  Google Scholar 

  • Janne J, Alhonen L, Leinonen P (1991) Polyamines: from molecular biology to clinical application. Ann Med 23:241–259

    Article  CAS  PubMed  Google Scholar 

  • Jänne J, Alhonen L, Pietilä M, Keinänen TA (2004) Genetic approaches to the cellular functions of polyamines in mammals. Eur J Biochem 271:877–894

    Article  PubMed  CAS  Google Scholar 

  • Johnson RM (2005) Polyamines, their biochemistry and role in neoplasia. Proc West Pharmacol Soc 48:21–23

    PubMed  Google Scholar 

  • Kagoshima M, Ito K, Cosio B, Adcock IM (2003) Glucocorticoid suppression of nuclear factor-κB: a role for histone modifications. Biochem Soc Trans 31(1):60–65

    Article  CAS  PubMed  Google Scholar 

  • Karin M (1998) New twists in gene regulation by glucocorticoid receptor: is DNA binding dispensable? Cell 93(4):487–490

    Article  CAS  PubMed  Google Scholar 

  • Kelley EE, Wagner B, Buettner G, Burns C (1999) Nitric oxide inhibits iron-induced lipid peroxidation in HL-60 cells. Arch Biochem Biophys 319:402–407

    Google Scholar 

  • Kepka-Lenhart D, Mistry SK, Wu G, Morris SM (2000) Arginase I: a limiting factor for nitric oxide and polyamine synthesis by activated macrophages? Am J Physiol Regul Integr Comp Physiol 279(6):R2237–R2242

    CAS  PubMed  Google Scholar 

  • Kerr JF, Wyllie AH, Currie AR (1972) Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. Br J Cancer 26(4):239–257

    CAS  PubMed  Google Scholar 

  • Kim YM, Talanian RV, Billiar TR (1997) Nitric oxide inhibits apoptosis by preventing increases in caspase-3-like activity via two distinct mechanisms. J Biol Chem 272(49):31138–31148

    Article  CAS  PubMed  Google Scholar 

  • Kishimoto M, Fujiki R, Takezawa S, Sasaki Y, Nakamura T, Yamaoka K, Katigawa H, Kato S (2006) Nuclear receptors mediated gene regulation through chromatin remodeling and histone modifications. Endocrinol J 53(2):157–172

    CAS  Google Scholar 

  • Liao CP, Lasbury ME, Wang SH, Zhang C, Durant PJ, Tschang D, Lee CH (2006) Inflammatory cells are sources of polyamines that induce alveolar macrophage to undergo apoptosis during pneumocystis pneumonia. J Eukaryot Microbiol 53(S1):S134–S135

    Article  CAS  PubMed  Google Scholar 

  • Lill-Elghanian D, Schwartz K, King L, Fraker P (2002) Glucocorticoid-induced apoptosis in early B cells from human bone marrow. Exp Biol Med 227:763–770

    CAS  Google Scholar 

  • Lim HY, Muller N, Herold MJ, van den Brandt J, Reichardt HM (2007) Glucocorticoids exert opposing effects on macrophage function dependent on their concentration. Immunology 122:47–53

    Article  CAS  PubMed  Google Scholar 

  • Liu Y, Fiskum G, Schubert D (2002) Generation of reactive oxygen species by the mitochondrial electron transport chain. J Neurochem 80:780–787

    Article  CAS  PubMed  Google Scholar 

  • Lu NZ, Cidlowski JA (2004) The origin and functions of multiple human glucocorticoid receptor isoforms. Ann NY Acad Sci 1024:102–123

    Article  CAS  PubMed  Google Scholar 

  • Maccarrone M, Bari MN, Battista N, Di Rienzo M, Falciglia K, Finazzi Agro A (2001) Oxidation products of polyamines induce mitochondrial uncoupling and cytochrome c release. FEBS Lett 507(1):30–34

    Article  CAS  PubMed  Google Scholar 

  • Maiuri MC, Tajana G, Iuvone T, De Stefano D, Mele G, Ribecco MT, Cinelli MP, Romano MF, Turco MC, Carnuccio R (2004) Nuclear factor-κB regulates inflammatory cell apoptosis and phagocytosis in rat carrageenin-sponge implant model. Am J Pathol 165(1):115–126

    CAS  PubMed  Google Scholar 

  • Matthews HR (1993) My favorite molecule: polyamines, chromatin structure and transcription. Bio Essays 15(8):561–566

    CAS  Google Scholar 

  • McKay LI, Cidlowski JA (1998) Cross-talk between nuclear factor-κB and the steroid hormone receptors: mechanisms of mutual antagonism. Mol Endocrinol 12(1):45–56

    Article  CAS  PubMed  Google Scholar 

  • Miller AL, Johnson HB, Medh DR, Townsend MC, Thompson BE (2002) Glucocorticoids and polyamine inhibitors synergize to kill human leukemic CEM cells. Neoplasia 4(1):68–81

    Article  CAS  PubMed  Google Scholar 

  • Moinard CH, Cynober L, de Bandt JP (2005) Polyamines: metabolism and implications in human diseases. Clin Nutr 24:184–197

    Article  CAS  PubMed  Google Scholar 

  • Moylan JS, Reid MB (2007) Oxidative stress, chronic diseases, and muscle wasting. Muscle Nerve 35:411–429

    Article  CAS  PubMed  Google Scholar 

  • Murrray-Stewart T, Wang Y, Devereux W, Robert A, Casero RA (2002) Cloning and characterization of multiple human polyamine oxidase splice variants that code for isoenzymes with different biochemical characteristics. Biochem J 368:673–677

    Article  Google Scholar 

  • Novac N, Baus D, Dostert A, Heinzel T (2006) Competition between glucocorticoid receptor and NF-κB for control of the human FasL promoter. FASEB J 20:1074–1081

    Article  CAS  PubMed  Google Scholar 

  • Ott M, Gogvadze V, Zhivotovsky SB (2007) Mitochondria, oxidative stress and cell death. Apoptosis 12:913–922

    Article  CAS  PubMed  Google Scholar 

  • Oyanagui Y (1984) Anti-inflammatory effects of polyamines in serotonin and carrageenan paw edemata—possible mechanism to increase vascular permeability inhibitory protein level which is regulated by glucocorticoids and superoxide radical. Agents Actions 14(2):228–237

    Article  CAS  PubMed  Google Scholar 

  • Panagiotidis CA, Artandi S, Calame K, Silverstein SJ (1995) Polyamines alter sequence specific DNA–protein interactions. Nucleic Acids Res 23(10):1800–1809

    Article  CAS  PubMed  Google Scholar 

  • Papavassiliou AG (1995) Transcription factors. N Engl J Med 332:45–47

    Article  CAS  PubMed  Google Scholar 

  • Paul-Clark MJ, Roviezzo F, Flower RJ, Cirino G, Del Soldato P, Adcock IM, Perretti M (2003) Glucocorticoid receptor nitration leads to enhanced anti-inflammatory effects of novel steroid ligands. J Immunol 171:3245–3252

    CAS  PubMed  Google Scholar 

  • Pavlovic DD, Uzunova P, Galabova T, Peneva V, Sokolova Z, Bjelakovic G, Ribarov S (1992) Polyamines as modulators of lipoperoxidation. Gen Physiol Biophys 11(2):203–211

    CAS  PubMed  Google Scholar 

  • Pegg AE (1986) Recent advances in the biochemistry of polyamines in eukaryotes. Biochem J 234:249–262

    CAS  PubMed  Google Scholar 

  • Pegg AE (1988) Polyamine metabolism and its importance in neoplastic growth and as a target of chemotherapy. Cancer Res 48:759–774

    CAS  PubMed  Google Scholar 

  • Pegg AE, Feith DJ (2007) Polyamines and neoplastic growth. Biochem Soc Trans 35:295–299

    Article  CAS  PubMed  Google Scholar 

  • Pouline R, Pelletier PRG, Pegg AE (1995) Induction of apoptosis by excessive polyamine accumulation in ornithine decarboxylase-overproducing L1210 cells. Biochem J 311:723–727

    Google Scholar 

  • Pelta J, Livolant F, Sikorav JL (1996) DNA aggregation induced by polyamines and cobalthexamine. J Biol Chem 271(10):5656–5662

    Article  CAS  PubMed  Google Scholar 

  • Penning LC, Schipper RG, Vercammen D, Verhofstad AAJ, Denecker T, Beyaert R, Vandenabeele P (1998) Sensitization of TNF-induced apoptosis with polyamine synthesis inhibitors in different human and murine tumour cell lines. Cytokine 10(6):423–431

    Article  CAS  PubMed  Google Scholar 

  • Pfeffer LM, Yang CH, Murt A, McCormack SA, Viar MJ, Ray RM, Johnson LR (2001) Polyamine depletion induces rapid NF-kappa B activation in IEC-6 cells. J Biol Chem 276(49):45909–45913

    Article  CAS  PubMed  Google Scholar 

  • Pickle S (2005) Glucocorticoid-induced apoptosis: the role of reactive oxygen species and the proteasome. A thesis submitted to the Miami University Honor Program, May, Oxford, Ohio

  • Pitzalis C, Pipitone N, Perretti M (2002) Regulation of leukocyte–endothelial interactions by glucocorticoids. Ann N Y Acad Sci 966:108–118

    Article  CAS  PubMed  Google Scholar 

  • Pledgie A, Huang Y, Hacker A, Zhang Z, Woster PM, Davidson NE, Casero RA (2005) Spermine oxidase SMO(PAOh1), not N1-acetylpolyamine oxidase PAO, is the primary source of cytotoxic H2O2 in polyamine analogue-treated human breast cancer cell lines. J Biol Chem 280(48):39843–39851

    Article  CAS  PubMed  Google Scholar 

  • Ploner C, Schmidt S, Presul E, Renner K, Schrocksnadel K, Rainer J, Riml S, Kofler R (2005) Glucocorticoid-induced apoptosis and glucocorticoid resistance in acute lymphoblastic leukemia. J Steroid Biochem Mol Biol 93:153–160

    Article  CAS  PubMed  Google Scholar 

  • Pollard KJ, Samuels ML, Crowley KA, Hansen JC, Peterson CL (1999) Functional interaction between GCN5 and polyamines: a new role for core histone acetylation. EMBO J 18(20):5622–5633

    Article  CAS  PubMed  Google Scholar 

  • Psarra AMG, Solakidi S, Sekeris CE (2006) The mitochondrion as a primary site of action of steroid and thyroid hormones: presence and action of steroid and thyroid hormone receptors in mitochondria of animal cells. Mol Cell Endocrinol 246(1–2):21–33

    Article  CAS  PubMed  Google Scholar 

  • Que FG, Gores GJ (1996) Cell death by apoptosis: basic concepts and disease relevance for the gastroenterologist. Gastroenterology 110:1238–1243

    Article  CAS  PubMed  Google Scholar 

  • Ray RM, Viar MJ, Yuan Q, Johnson LR (2000) Polyamine depletion delays apoptosis of rat intestinal epithelial cells. Am J Physiol Cell Physiol 278(3):C480–C489

    CAS  PubMed  Google Scholar 

  • Rhen T, Cildowski AJ (2005) Anti-inflammatory action of glucocorticoids—new mechanisms for old drugs. N Engl J Med 353(16):1711–1723

    Article  CAS  PubMed  Google Scholar 

  • Roussel D, Dumas JF, Simard G, Malthiery Y, Ritz P (2004) Kinetics and control of oxidative phosphorylation in rat liver mitochondria after dexamethasone treatment. Biochem J 382:491–499

    Article  CAS  PubMed  Google Scholar 

  • Salvi M, Toninello A (2004) Effects of polyamines on mitochondrial (Ca2+) transport. Biochim Biophys Acta 1661(2):113–124

    Article  CAS  PubMed  Google Scholar 

  • Satriano J, Ishizuka S, Archer DC, Blantz RC, Kelly CJ (1999) Regulation of intracellular polyamine biosynthesis and transport by NO and cytokines TNF-α and IFN-γ. Am J Physiol 276(4 Pt 1):C892–C899

    CAS  PubMed  Google Scholar 

  • Sava IG, Battaglia V, Rossi CA, Salvi M, Toninello A (2006) Free radical scavenging action of the natural polyamine spermine in rat liver mitochondria. Free Radic Biol Med 41(8):1272–1281

    Article  CAS  PubMed  Google Scholar 

  • Schäcke H, Döcke WD, Asadullah K (2002) Mechanisms involved in the side effects of glucocorticoids. Pharmacol Ther 96(1):23–43

    Article  PubMed  Google Scholar 

  • Schäfer SC, Wallerath T, Closs EI, Schmidt C, Schwarz PM, Förstermann U, Lehr HA (2005) Dexamethasone suppresses eNOS and CAT-1 and induces oxidative stress in mouse resistance arterioles. Am J Physiol Heart Circ Physiol 288(1):H436–H444

    Google Scholar 

  • Schiller M, Blank N, Heyder P, Herrmann M, Gaipl US, Kalden JR, Lorenz HM (2005) Induction of apoptosis by spermine-metabolites in primary human blood cells and various tumor cell lines. Apoptosis 10(5):1151–1162

    Article  CAS  PubMed  Google Scholar 

  • Schuber F (1989) Influence of polyamines on membrane functions. Biochem J 260:1–10

    CAS  PubMed  Google Scholar 

  • Seiler N (1995) Polyamine oxidase, properties and functions. Prog Brain Res 106:333–344

    Article  CAS  PubMed  Google Scholar 

  • Seiler N, Atanassov CL (1994) The natural polyamines and the immune system. Prog Drug Res 43:87–141

    CAS  PubMed  Google Scholar 

  • Seiler N, Raul F (2005) Polyamines and apoptosis. J Cell Mol Med 9(3):623–642

    Article  CAS  PubMed  Google Scholar 

  • Shearer JD, Richards JR, Mills CD, Caldwell MD (1997) Differential regulation of macrophage arginine metabolism: a proposed role in wound healing. Am J Physiol 272(35):E181–E190

    CAS  PubMed  Google Scholar 

  • Sionov RV, Cohen O, Kfir S, Zilberman Y, Yefenof E (2006a) Role of mitochondrial glucocorticoid receptor in glucocorticoid-induced apoptosis. J Exp Med 203(1):189–201

    Article  CAS  PubMed  Google Scholar 

  • Sionov RV, Kfir S, Zafrir E, Cohen O, Zilberman Y, Yefenof E (2006b) Glucocorticoid-induced apoptosis revisited. A novel role for glucocorticoid receptor translocation to the mitochondria. Cell Cycle 5(10):1017–1026

    CAS  PubMed  Google Scholar 

  • Soulet D, Rivest S (2003) Polyamines play a critical role in the control innate immune response in the mouse central nervous system. J Cell Biol 162(2):257–268

    Article  CAS  PubMed  Google Scholar 

  • Southan GJ, Szabo C, Thiemermann C (1994) Inhibition of the induction of nitric oxide synthase by spermine is modulated by aldehyde dehydrogenase. Biochem Biophys Res Comm 203:1638–1644

    Article  CAS  PubMed  Google Scholar 

  • Stanic I, Facchini A, Borzì RM, Vitellozzi R, Stefanelli C, Goldring MB, Guarnieri C, Facchini A, Flamigni F (2006) Polyamine depletion inhibits apoptosis following blocking of survival pathways in human chondrocytes stimulated by tumor necrosis factor-α. J Cell Physiol 206(1):138–146

    Article  CAS  PubMed  Google Scholar 

  • Stefanelli C, Bonavita F, Stanic I, Mignani M, Facchini A, Pignatti C, Flamigni F, Caldarera CM (1998) Spermine causes caspase activation in leukaemia cells. FEBS Lett 437(3):233–236

    Article  CAS  PubMed  Google Scholar 

  • Stefanelli C, Stanic I, Zini M, Bonavita F, Flamigni F, Zambonin L, Landi L, Pignatti C, Guarnieri C, Caldarera CM (2000) Polyamines directly induce release of cytochrome c from heart mitochondria. Biochem J 347(Pt 3):875–880

    Article  CAS  PubMed  Google Scholar 

  • Struhl K (1998) Histone acetylation and transcriptional regulatory mechanisms. Genes Dev 12(5):599–606

    Article  CAS  PubMed  Google Scholar 

  • Szabo C, Southan GJ, Wood E, Thiemermann C, Vanne JR (1994a) Inhibition by spermine of the induction of nitric oxide synthase in J774.2 macrophages: requirement of a serum factor. Br J Pharmacol 112(2):355–356

    CAS  PubMed  Google Scholar 

  • Szabo C, Southan G, Thiemermann C, Vane J (1994b) The mechanism of the inhibitory effect of polyamines on the induction of nitric oxide synthase: role of aldehyde metabolites. Br J Pharmacol 113:757–766

    CAS  PubMed  Google Scholar 

  • Tabor CW, Tabor H (1984) Polyamines. Annu Rev Biochem 53:749–790

    Article  CAS  PubMed  Google Scholar 

  • Takao K, Rickhag M, Hegardt C, Oredsson S, Persson L (2006) Induction of apoptotic cell death by putrescine. Int J Biochem Cell Biol 38(4):621–628

    Article  CAS  PubMed  Google Scholar 

  • Tantini B, Fiumana E, Cetrullo S, Pignatti C, Bonavita F, Shantz LM, Giordano E, Muscari C, Flamigni F, Guarnieri C, Stefanelli C, Caldarera CM (2006) Involvement of polyamines in apoptosis of cardiac myoblasts in a model of simulated ischemia. J Mol Cell Cardiol 40(6):775–782

    Article  CAS  PubMed  Google Scholar 

  • Thomas T, Thomas JT (2001) Polyamines in cell growth and cell death: molecular mechanisms and therapeutic applications. Cell Mol Life Sci 58:244–258

    Article  CAS  PubMed  Google Scholar 

  • Thornberry NA, Lazebnik Y (1998) Caspases: enemies within. Science 281:1312–1316

    Article  CAS  PubMed  Google Scholar 

  • Tomitori H, Usui T, Saeki N, Ueda S, Kase H, Nishimura K, Kashiwagi K, Igarashi K (2005) Polyamine oxidase and acrolein as novel biochemical markers for diagnosis of cerebral stroke. Stroke 36:2609–2616

    Article  CAS  PubMed  Google Scholar 

  • Toninello A, Dalla Via L, Testa S, Siliprandi D, Siliprandi N (1990) Transport and action of spermine in rat heart mitochondria. Cardioscience 1:287–294

    CAS  PubMed  Google Scholar 

  • Toninello A, Dalla Via L, Siliprandi D, Garlid KD (1992) Evidence that spermine, spermidine and putrescine are transported electrophoretically in mitochondria by a specific polyamine uniporter. J Biol Chem 267:18393–18397

    CAS  PubMed  Google Scholar 

  • Toninello A, Salvi M, Mondovi B (2004) Interaction of biologically active amines with mitochondria and their role in the mitochondrial-mediated pathway of apoptosis. Curr Med Chem 11(17):2349–2374

    CAS  PubMed  Google Scholar 

  • Tonomura N, McLaughlin K, Grimm L, Goldsby RA, Osbourne BA (2003) Glucocorticoid-induced apoptosis of thymocytes: requirement of proteasome-dependent mitchondrial activity. J Immunol 170:2469–2478

    CAS  PubMed  Google Scholar 

  • Tuckermann JP, Kleiman A, McPherson KG, Reichardt HM (2005) Molecular mechanisms of glucocorticoids in the control of inflammation and lymphocyte apoptosis. Crit Rev Clin Lab Sci 42(1):71–104

    Article  CAS  PubMed  Google Scholar 

  • Vujcic S, Diegelman P, Bacchi CJ, Kramer DL, Porter CW (2002) Identification and characterization of a novel flavin-containing spermine oxidase of mammalian cell origin. Biochem J 367:665–675

    Article  CAS  PubMed  Google Scholar 

  • Vujcic S, Liang P, Diegelman P, Kramer DL, Porter CW (2003) Genomic identification and biochemical characterization of the mammalian polyamine oxidase involved in polyamine back-conversion. Biochem J 370:19–28

    Article  CAS  PubMed  Google Scholar 

  • Wallace HM, Fraser AV (2004) Inhibitors of polyamine metabolism: review article. Amino Acids 26(4):353–365

    Article  CAS  PubMed  Google Scholar 

  • Wallace HM, Fraser AV, Hughes A (2003) A perspective of polyamine metabolism. Biochem J 376:1–14

    Article  CAS  PubMed  Google Scholar 

  • Wang Y, Casero RA (2006) Mammalian polyamine catabolism: a therapeutic target, a pathological problem, or both? J Biochem 139(1):17–25

    Article  CAS  PubMed  Google Scholar 

  • Wang Y, Murray-Stewart T, Devereux W, Hacker A, Frydman B, Woster PM, Casero RA (2003) Properties of purified recombinant human polyamine oxidase, PAOh1/SMO. Biochem Biophys Res Commun 304:605–611

    Article  CAS  PubMed  Google Scholar 

  • Wang D, Mülle N, Kirsty G, McPherson KG, Reichardt HM (2006) Glucocorticoids engage different signal transduction pathways to induce apoptosis in thymocytes and mature T cells. J Immunol 176:1695–1702

    CAS  PubMed  Google Scholar 

  • Webb MS, Miller LA, Johnson HB, Fofanov Y, Li T, Wood GT, Thompson EB (2003) Gene networks in glucocorticoid-evoked apoptosis of leukemic cells. J Steroid Biochem Mol Biol 85:183–193

    Article  CAS  PubMed  Google Scholar 

  • Wei J, Guo H, Gao C, Kuo PC (2004) Peroxide-mediated chromatin remodelling of a nuclear factor κB site in the mouse inducible nitric oxide synthase promoter. Biochem J 377:809–818

    Article  CAS  PubMed  Google Scholar 

  • Wu C (1997) Chromatin remodeling and the control of gene expression. J Biol Chem 272(45):28171–28174

    Article  CAS  PubMed  Google Scholar 

  • Yanagawa K, Yamashita T, Yada K, Ohira M, Ishikawa T, Yano Y, Otani S, Sowa M (1998) The antiproliferative effect of HGF on hepatoma cells involves induction of apoptosis with increase in intracellular polyamine concentration levels. Oncol Rep 5:185–190

    CAS  PubMed  Google Scholar 

  • Yuan Q, Ray RM, Johnson LR (2002) Polyamine depletion prevents camptothecin induced apoptosis by inhibiting the release of cytochrome c. Am J Physiol Cell Physiol 282(6):C1290–C1297

    CAS  PubMed  Google Scholar 

  • Zhang M, Caragine T, Wang H, Cohen SP, Botchkina G, Soda K, Bianchi M, Ulrich P, Cerami A, Sherry B, Tracey JK (1997) Spermine inhibits proinflammatory cytokine synthesis in human mononuclear cells: a counterregulatory mechanism that restrains the immune response. J Exp Med 185(1):1759–1768

    Article  CAS  PubMed  Google Scholar 

  • Zhang M, Tracey HW, Kevin J (2000) Regulation of macrophage activation and inflammation by spermine: a new chapter in an old story. Crit Care Med 28(4 Suppl):N60–N66

    Article  CAS  PubMed  Google Scholar 

  • Zhang W, Ramdas L, Shen W, Song SW, Hu L, Hamilton SR (2003) Apoptotic response to 5-fluorouracil treatment is mediated by reduced polyamines, non-autocrine Fas ligand, and induced tumor necrosis factor receptor. Cancer Biol Ther 2(5):572–578

    CAS  PubMed  Google Scholar 

  • Zou T, Rao NJ, Guo X, Liu L, Zhang MH, Strauch DE, Bass BL, Wang JY (2004) NF-κB-mediated IAP expression induces resistance of intestinal epithelial cells to apoptosis after polyamine depletion. Am J Physiol Cell Physiol 286:C1009–C1018

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to G. Bjelaković.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bjelaković, G., Stojanović, I., Jevtović Stoimenov, T. et al. Metabolic correlations of glucocorticoids and polyamines in inflammation and apoptosis. Amino Acids 39, 29–43 (2010). https://doi.org/10.1007/s00726-010-0489-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00726-010-0489-3

Keywords

Navigation