Polyamines in aging and disease

Nadège Minois, Didac Carmona-Gutierrez, Frank Madeo, Nadège Minois, Didac Carmona-Gutierrez, Frank Madeo

Abstract

Polyamines are polycations that interact with negatively charged molecules such as DNA, RNA and proteins. They play multiple roles in cell growth, survival and proliferation. Changes in polyamine levels have been associated with aging and diseases. Their levels decline continuously with age and polyamine (spermidine or high-polyamine diet) supplementation increases life span in model organisms. Polyamines have also been involved in stress resistance. On the other hand, polyamines are increased in cancer cells and are a target for potential chemotherapeutic agents. In this review, we bring together these various results and draw a picture of the state of our knowledge on the roles of polyamines in aging, stress and diseases.

Conflict of interest statement

The authors of this manuscript have no conflict of interest to declare.

Figures

Figure 1. Putrescine, spermidine and spermine chemical…
Figure 1. Putrescine, spermidine and spermine chemical structure
Figure 2. Polyamine metabolism. Green: biosynthesis; blue:…
Figure 2. Polyamine metabolism. Green: biosynthesis; blue: catabolism; red: inhibitory protein; black: eIF5A synthesis from spermidine
Figure 3. Summary of the cellular mechanisms…
Figure 3. Summary of the cellular mechanisms of action of polyamines
Upon entering the cell, polyamines exhibit various functions in the cytoplasm, nucleus and mitochondria. Polyamines are involved in the regulation of cell death and cell proliferation as well as in protein synthesis at the level of both gene expression and translation. Recent evidence also assigned polyamines functions in cell reprogramming and autophagy regulation. Thus, polyamines are involved in a broad array of processes and cellular responses that suggest a complex and important role in the control of cellular life and death. PT: permeability transition; Δψm: mitochondrial membrane potential.

References

    1. Bachrach U. The early history of polyamine research. Plant Physiol Biochem. 2010;48:490–495.
    1. Hussain SS, Ali M, Ahmad M, Siddique KHM. Polyamines: Natural and engineered abiotic and biotic stress tolerance in plants. Biotechnol Adv. 2011 DOI: 10.1016/j.biotechadv.2011.01.003.
    1. Wallace HM, Fraser AV. Inhibitors of polyamine metabolism: Review article. Amino acids. 2004;26:353–365.
    1. Eisenberg T, Knauer H, Schauer A, Fussi H, Büttner S, Carmona-Gutierrez D, Ruckenstuhl C, Fahrenkrog B, Deszcz L, Hartl R, Weiskopf D, Grubeck-Loebenstein B, Herker E, et al. Induction of autophagy by spermidine promotes longevity. Nature Cell Biol. 2009;11:1305–1314.
    1. Wallace HM, Fraser AV, Hughes A. A perspective of polyamine metabolism. Biochem J. 2003;376:1–14.
    1. Jänne J, Alhonen L, Pietilä M, Keinänen TA. Genetic approaches to the cellular functions of polyamines in mammals. Eur J Biochem. 2004;271:877–894.
    1. Igarashi K, Kashiwagi K. Characteristics of cellular polyamine transport in prokaryotes and eukaryotes. Plant Physiol Biochem. 2010;48:506–512.
    1. Perez-Leal O, Merali S. Regulation of polyamine metabolism by translational control. Amino acids. 2011 DOI: 10.1007/s00726-011-1036-6.
    1. Higashi K, Ishigure H, Demizu R, Uemura T, Nishino K, Yamaguchi A, Kashiwagi K, Igarashi K. Identification of a spermidine excretion protein complex (MdtJI) in Escherichia coli. J Bacteriol. 2008;190:872–878.
    1. Teixeira MC, Cabrito TR, Hanif ZM, Vargas RC, Tenreiro S, Sá-Correia I. Yeast response and tolerance to polyamine toxicity involving the drug:H+ antiporter Qdr3 and the transcription factors Yap1 and Gcn4. Microbiol. 2010 DOI:10.1099/mic.0.043661-0.
    1. Fukuchi J, Hiipakka RA, Kokonitis JM, Nishimura K, Igarashi K, Liao S. TATA-binding protein-associated factor 7 regulates polyamine transport activity and polyamine-analog-induced apoptosis. J Biol Chem. 2004;279:29921–29929.
    1. Uemura T, Yerushalmi HF, Tsaprailis G, Stringer DE, Pastorian KE, Hawel L, III, Byus CV, Gerner EW. Identification and characterization of a diamine exporter in colon epithelial cells. J Biol Chem. 2008;283:26428–26435.
    1. Poulin R, Casero RA, Soulet D. Recent advances in the molecular biology of metazoan polyamine transport. Amino acids. 2011 DOI: 10.1007/s00726-011-0987-y.
    1. Scalabrino G, Ferioli ME. Polyamines in mammalian ageing: an oncological problem, too? A review. Mech Ageing Dev. 1984;26:149–164.
    1. Nishimura K, Shiina R, Kashiwagi K, Iagarashi K. Decrease in polyamines with aging and their ingestion from food and drink. J Biochem. 2006;139:81–90.
    1. Vivó M, de Vera N, Cortés R, Mengod G, Camón L, Martínez E. Polyamines in the basal ganglia of human brain. Influence of aging and degenerative movement disorders. Neurosci Lett. 2001;304:107–111.
    1. Liu P, Gupta N, Jing Y, Zhang H. Age-related changes in polyamines in memory-associated brain structures in rats. Neurosci. 2008;155:789–796.
    1. Fraga MF, Berdasco M, Borja Diego L, Rodríguez R, Cañal MJ. Changes in polyamine concentration associated with aging in Pinus radiata and Prunus persica. Tree Physiol. 2004;24:1221–1226.
    1. Serafini-Fracassini D, Del Luca S, Monti F, Poli F, Sacchetti G, Bregoli AM, Biondi S, Della Mea M. Transglutaminase activity during senescence and programmed cell death in the corolla of tobacco (Nicotiana tabacum) flowers. Cell Death Diff. 2002;9:309–321.
    1. Serafini-Fracassini D, Di Sandro A, Del Luca S. Spermine delays leaf senescence in Lactuca sativa and prevents the decay of chloroplast photosystems. Plant Physiol Biochem. 2010;48:602–611.
    1. Suppola S, Heikkinen S, Parkkinen JJ, Uusi-Oukari M, Korhonen VP, Keinänen T, Alhonen L, Jänne J. Concurrent overexpression of ornithine decarboxylase and spermidine/spermine N1-acetyltransferase further accelerates the catabolism of hepatic polyamines in transgenic mice. Biochem J. 2001;358:343–348.
    1. Cerrada-Gimenez M, Pietilä M, Loimas S, Pirinen E, Hyvönen MT, Keinänen TA, Jänne J, Alhonen L. Continuous oxidative stress due to activation of polyamine catabolism accelerates aging and protects against hepatotoxic insults. Transgenic Res. 2011;20:387–396.
    1. Soda K, Kano Y, Sakuragi M, Takao K, Lefor A, Konishi F. Long-term oral polyamine intake increases blood polyamine concentrations. J Nutr Sci Vitaminol. 2009;55:361–366.
    1. Soda K, Dobashi Y, Kano Y, Tsujinaka S, Konishi F. Polyamine-rich food decreases age-associated pathology and mortality in aged mice. Exp Gerontol. 2009;44:727–732.
    1. Alcázar R, Cuevas JC, Planas J, Zarza X, Bortolotti C, Carrasco P, Salinas J, Tiburcio AF, Altabella T. Integration of polaymines in the cold acclimation response. Plant Sci. 2011;180:31–38.
    1. Mohapatra S, Cherry S, Minocha R, Majumdar R, Thangavel P, Long S, Minocha SC. The response of high and low polyamine-inducing cell lines to aluminum and calcium stress. Plant Physiol Biochem. 2010;48:612–620.
    1. Wang J, Sun PP, Chen CL, Wang Y, Fu XZ, Liu JH. An arginine decarboxylase gene PtADC from Poncirus trifoliate confers abiotic stress tolerance and promotes primary root growth in Arabidopsis. J Exp Bot. 2011 DOI:10.1093/jxb/erq463.
    1. Gonzalez ME, Marco F, Gómez Minguet E, Carrasco-Sorli P, Blázquez MA, Carbonell J, Ruiz OA, Pieckenstain FL. Perturbation of spermine synthase gene expression and transcript profiling provide new insights on the role of the tetraamine spermine in Arabidopsis thaliana defense against Pseudomonas viridiflava. Plant Physiol. 2011 DOI:10.1104/pp.110.171413.
    1. Kaasinen SK, Oksman M, Alhonen L, Tanila H, Jänne J. Spermidine/spermine N1-acetyltransferase overexpression in mice induces hypoactivity and spatial learning impairment. Pharmacol Biochem Behav. 2004;78:35–45.
    1. Vigne P, Frelin C. The role of polyamines in protein-dependent hypoxic tolerance of Drosophila. BMC Physiol. 2008;8:22.
    1. Gomes-Trolin C, Nygren I, Aquilonius SM, Askmark H. Increased red blood cell polyamines in ALS and Parkinson's disease. Exp Neurol. 2002;177:515–520.
    1. Yatin SM, Yatin M, Aulick T, Ain KB, Butterfield DA. Alzheimer's amyloid β-peptide associated free radicals increase rat embryonic neuronal polyamine uptake and ornithine decarboxylase activity: protective effect of vitamin E. Neurosci Lett. 1999;263:17–20.
    1. Antony T, Hoyer W, Cherny D, Heim G, Jovin TM, Subramaniam V. Cellular polyamines promote the aggregation of α-synuclein. J Biol Chem. 2003;278:3235–3240.
    1. Grabenauer M, Bernstein SL, Lee JC, Wyttenbach T, Dupuis NF, Gray HB, Winkler JR, Bowers MT. Spermine binding to Parkinson's protein α-synuclein and its disease-related A30P and A53T mutants. J Phys Chem B. 2008;112:11147–11154.
    1. Lewandowski NM, Ju S, Verbitsky M, Ross B, Geddie ML, Rockenstein E, Adama A, Muhammad A, Vonsattel JP, Ringe D, Cote L, Lindquist S, Masliah E, et al. (2010) Polyamine pathway contributes to the pathogenesis of Parkinson disease. Proc Natl Acad Sci USA. 2010;107:16970–16975.
    1. Duan B, Wang YZ, Yang T, Chu XP, Yu Y, Huang Y, Cao H, Hansen J, Simon RP, Zhu MX, Xiong ZG, Xu TL. Extracellular spermine exacerbates ischemic neuronal injury through sensitization of ASIC1a channels to extracellular acidosis. J Neurosci. 2011;31:2101–2112.
    1. Bell MR, Belarde JA, Johnson HF, Aizenman CD. A neuroprotective role for polyamines in a Xenopus tadpole model of epilepsy. Nature Neurosci. 2011 DOI:10.1038/nn.2777.
    1. Jung YS, Kim SJ, Kwon DY, Kim YC. Metabolomic analysis of sulphur-containing substances and polyamines in regenerating rat liver. Amino Acids. 2011 DOI: 10.1007/s00726-011-0946-7.
    1. Puntambekar SS, Davis DS, Hawel L, III, Crane J, Byus CV, Carson MJ. Lps-induced Ccl2 expression and macrophage influx into the murine central nervous system is polyamine-dependent. Brain Behav Immun. 2011 DOI: 10.1016/j.bbi.2010.12.016.
    1. Soda K. Polyamine intake, dietary pattern, and cardiovascular disease. Med Hypotheses. 2010;75:299–301.
    1. Lentini A, Tabolacci C, Mattioli P, Provenzano B, Beninati S. Spermidine delays eye lens opacification in vitro by suppressing transglutaminase-catalyzed crystalline cross-linking. Protein J. 2011;30:109–114.
    1. Guo X, Harada C, Namekata K, Kimura A, Mitamura Y, Yoshida H, Matsumoto Y, Harada T. Spermidine alleviates severity of murine experimental autoimmune encephalomyelitis. Inves Ophtalmol Vis Sci. 2011;52:2696–2703.
    1. Nishimura K, Yanase T, Nakagawa H, Matsuo S, Ohnishi Y, Yamasaki S. Effect of polyamine-deficient chow on Trypanosoma brucei brucei infection in rats. J Parasitol. 2009;95:781–786.
    1. Reyes-Becerril M, Ascencio-Valle F, Tovar-Ramírez D, Meseguer J, Esteban MA. Effects of polyamines on cellular innate immune response and the expression of immune-relevant genes in gilthead seabream leucocytes. Fish Shellfish Immunol. 2010;30:248–254.
    1. Uehara Y, Takahashi Y, Berberich T, Miyazaki A, Takahashi H, Matsui K, Ohme-Takagi M, Saitoh H, Terauchi R, Kusano T. Tobacco ZFT1, a transcriptional repressor with a Cys2/His2 type zinc finger motif that functions in spermine-signaling pathway. Plant Mol Biol. 2005;59:435–448.
    1. Shah P, Nanduri B, Swiatlo E, Ma Y, Pendarvis K. Polyamine biosynthesis and transport mechanisms are crucial for fitness and pathogenesis of Streptococcus pneumonia. Microbiol. 2011;157:504–515.
    1. Hibshoosh H, Johnson M, Weinstein IB. Effects of overexpression of ornithine decarboxylase (ODC) on growth control and oncogene-induced cell transformation. Oncogene. 1991;6:739–743.
    1. Auvinen M, Paasinen A, Andersson LC, Hölttä E. Ornithine decarboxylase activity is critical for cell transformation. Nature. 1992;360:355–358.
    1. Alhonen L, Halmekytö M, Kosma VM, 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;63:402–404.
    1. Bernacki RJ, Oberman EJ, Sewerymiak KE, Atwood A, Bergeron RJ, Porter CW. Preclinical antitumor efficacy of the polyamine analogue N1, N11-diethylnorspermine administered by multiple injection or continuous infusion. Clin Cancer Res. 1995;1:847–857.
    1. Kramer DL, Chang BD, Chen Y, Diegelman P, Alm K, Black AR, Roninson IB, Porter CW. Polyamine depletion in human melanoma cells leads to G1 arrest associated with induction of p21WAF1/CIP1/SDI1, changes in the expression of p21-regulated genes, and a senescence-like phenotype. Cancer Res. 2001;61:7754–7762.
    1. 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;187:493–497.
    1. 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;55:4205–4209.
    1. Shantz LM, Guo Y, Sawicki JA, Pegg AE, O'Brien TG. Overexpression of a dominant-negative ornithine decarboxylase in mouse skin: effect on enzyme activity and papilloma formation. Carcinogenesis. 2002;23:657–664.
    1. Pietilä M, Parkkinen JJ, Alhonen L, Jänne J. Relation of skin polyamines to the hairless phenotype in transgenic mice overexpressing spermidine/spermine N1-acetyltransferase. J Invest Dermatol. 2001;116:801–805.
    1. 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;23:359–364.
    1. 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;61:6073–6081.
    1. 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;63:3945–3954.
    1. Gerner EW, Meyskens FL., Jr Polyamines and cancer: old molecules, new understanding. Nat Rev Cancer. 2004;4:781–792.
    1. Casero RA, Jr, Marton LJ. Targeting polyamine metabolism and function in cancer and other hyperproliferative diseases. Nat Rev Drug Discov. 2007;6:373–390.
    1. Amendola R, Cervelli M, Fratini E, Polticelli F, Sallustio DE, Mariottini P. Spermine metabolism and anticancer therapy. Curr Cancer Drug Targets. 2009;9:118–130.
    1. Senanayake MDT, Amunugama H, Boncher TD, Casero RA, Jr, Woster PM. Design of polyamine-based therapeutic agents: new targets and new directions. Essays Biochem. 2009;46:77–94.
    1. Szumilak M, Szulawska-Mroczek A, Koprowska K, Stasiak M, Lewgowd W, Stanczak A, Czyz M. Synthesis and in vitro biological evaluation of new polyamine conjugates as potential anticancer drugs. Eur J Med Chem. 2010;45:5744–5751.
    1. Babbar N, Gerner EW. Targeting polyamines and inflammation for cancer prevention. In: Senn HJ, Otto F, editors. Clinical Cancer Prevention. Springer-Verlag; 2011. pp. 49–64.
    1. Beninati S, Piacentini M, Cocuzzi ET, Autuori F, Folk JE. Polyamines as physiological substrates for transglutaminases. Biochim Biophys Acta. 1988;952:325–333.
    1. Lentini A, Tabolacci C, Provenzano B, Rossi S, Beninati S. Phytochemicals and protein – polyamine conjugates by transglutaminase as chemopreventive and chemotherapeutic tools in cancer. Plant Physiol Biochem. 2010;48:627–633.
    1. Wolter F, Ulrich S, Stein J. Molecular mechanisms of the chemopreventive effects of resveratrol and its analogs in colorectal cancer: key role of polyamine? J Nutr. 2004;134:3219–3222.
    1. Hofseth LJ, Singh UP, Singh NP, Nagarkatti M, Nagarkatti PS. Taming the beast within: resveratrol suppresses colitis and prevents colon cancer. Aging. 2010;2:183–184.
    1. Saunders FR, Wallace HM. On the natural chemoprevention of cancer. Plant Physiol. Biochem. 2010;48:621–626.
    1. Parashar V, Rogina B. dSir2 mediates the increased spontaneous physical activity in flies on calorie restriction. Aging. 2009;1:529–541.
    1. Bauer JH, Morris SN, Chang C, Flatt T, Wood JG, Helfand SL. dSir2 and Dmp53 interact to mediate aspects of CR-dependent lifespan extension in D. melanogaster. Aging. 2009;1:38–48.
    1. Wood JG, Rogina B, Lavu S, Howitz K, Helfand SL, Tatar M, Sinclair D. Sirtuin activators mimic caloric restriction and delay ageing in metazoans. Nature. 2004;430:686–689.
    1. Bass TM, Weinkove D, Houthoofd K, Gems D, Partridge L. Effects of resveratrol on lifespan in Drosophila melanogaster and Caenorhabditis elegans. Mech Ageing Dev. 2007;128:546–552.
    1. Baur JA, Pearson KJ, Price NL, Jamieson HA, Lerin C, Kalra A, Prabhu VV, Allard JS, Lopez-Lluch G, Lewis K, Pistell PJ, Poosala S, Becker KG, et al. Resveratrol improves health and survival of mice on a high-calorie diet. Nature. 2006;444:337–342.
    1. Pearson KJ, Baur JA, Lewis KN, Peshkin L, Price NL, Labinskyy N, Swindell WR, Kamara D, Minor RK, Perez E, Jamieson HA, Zhang Y, Dunn SR, et al. Resveratrol delays age-related deterioration and mimics transcriptional aspects of dietary restriction without extending life span. Cell Metab. 2008;8:157–168.
    1. Miller RA, Harrison DE, Astle CM, Baur JA, Boyd AR, de Cabo R, Fernandez E, Flurkey K, Javors MA, Nelson JF, Orihuela CJ, Pletcher S, Sharp ZD, et al. Rapamycin, but not resveratrol or simvastatin, extends lifespan of genetically heterogeneous mice. J Gerontol A Biol Sci Med Sci. 2010;66:191–201.
    1. Armour SM, Baur JA, Hsieh SN, Land-Bracha A, Thomas SM, Sinclair DA. Inhibition of mammalian S6 kinase by resveratrol suppresses autophagy. Aging. 2009;1:515–528.
    1. Blagosklonny MV. Inhibition of S6K by resveratrol: in search of the purpose. Aging. 2009;1:511–514.
    1. Chondrogianni N, Kapeta S, Chinou I, Vassilatou K, Papassideri I, Gonos ES. Anti-ageing and rejuvenating effects of quercetin. Exp Gerontol. 2010;45:763–771.
    1. Martelli AM, Evangelisti C, Chiarini F, McCubrey JA. The phosphatidylinositol 3-kinase/Akt/mTOR signaling network as a therapeutic target in acute myelogenous leukemia patients. Oncotarget. 2010;1:89–103.
    1. Powers RW, 3rd, Kaeberlein M, Caldwell SD, Kennedy BK, Fields S. Extension of chronological lifespan in yeast by decreased TOR pathway signaling. Genes Dev. 2006;20:174–184.
    1. Alvers AL, Wood MS, Hu D, Kaywell AC, Dunn WA, Jr, Aris JP. Autophagy is required for extension of yeast chronological life span by rapamycin. Autophagy. 2009;5:847–849.
    1. Bjedov I, Toivonen JM, Kerr F, Slack C, Jacobson J, Foley A, Partridge L. Mechanisms of lifespan extension by rapamycin in the fruit fly Drosophila melanogaster. Cell Metab. 2010;11:35–46.
    1. Harrison DE, Strong R, Sharp ZD, Nelson JF, Astle CM, Flurkey K, Nadon NL, Wilkinson JE, Frenkel K, Carter CS, Pahor M, Javors MA, Fernandez E, et al. Rapamycin fed late in life extends lifespan in genetically heterogeneous mice. Nature. 2009;460:392–395.
    1. Pan Y, Shadel GS. Extension of chronological life span by reduced TOR signaling requires down-regulation of Sch9p and involves increased mitochondrial OXPHOS complex density. Aging. 2009;1:131–145.
    1. Demidenko ZN, Zubova SG, Bukreeva EI, Pospelov VA, Pospelova TV, Blagosklonny MV. Rapamycin decelerates cellular senescence. Cell Cycle. 2009;8:1888–1895.
    1. Ruckenstuhl C, Carmona-Gutierrez D, Madeo F. The sweet taste of death: glucose triggers apoptosis during yeast chronological aging. Aging. 2010;2:643–649.
    1. Ruckenstuhl C, Büttner S, Carmona-Gutierrez D, Eisenberg T, Kroemer G, Sigrist SJ, Fröhlich KU, Madeo F. The Warburg effect suppresses oxidative stress induced apoptosis in a yeast model for cancer. PLoS One. 2009;4:e4592.
    1. Bjelaković G, Stojanović I, Jevtović Stoimenov T, Pavlović D, Kocić G, Rossi S, Tabolacci C, Nikolić J, Sokolović D, Bjelakovic LJ. Metabolic correlations of glucocorticoids and polyamines in inflammation and apoptosis. Amino Acids. 2010;39:29–43.
    1. Salvi M, Toninello A. Effects of polyamines on mitochondrial Ca(2+) transport. Biochim Biophys Acta. 2004;1661:113–124.
    1. Heeren G, Rinnerthaler M, Laun P, von Seyerl P, Kössler S, Klinger H, Hager M, Bogengruber E, Jarolim S, Simon-Nobbe B, Schüller C, Carmona-Gutierrez D, Breitenbach-Koller L, et al. The mitochondrial ribosomal protein of the large subunit, Afo1p, determines cellular longevity through mitochondrial back-signaling via TOR1. Aging. 2009;1:622–636.
    1. Stefanelli C, Stanic' I, Zini M, Bonavita F, Flamigni F, Zambonin L, Landi L, Pignatti C, Guarnieri C, Caldarera CM. Polyamines directly induce release of cytochrome c from heart mitochondria. Biochem J. 2000;347:875–880.
    1. Maccarrone M, Bari M, Battista N, Di Rienzo M, Falciglia K, Finazzi Agrò A. Oxidation products of polyamines induce mitochondrial uncoupling and cytochrome c release. FEBS Lett. 2001;507:30–34.
    1. Carmona-Gutierrez D, Bauer MA, Ring J, Knauer H, Eisenberg T, Büttner S, Ruckenstuhl C, Reisenbichler A, Magnes C, Rechberger GN, Birner-Gruenberger R, Jungwirth H, Fröhlich KU, et al. The propeptide of yeast cathepsin D inhibits programmed necrosis. Cell Death Dis. 2011 DOI: 10.1038/cddis.2011.43.
    1. Liaudet-Coopman E, Beaujoin M, Derocq D, Garcia M, Glondu-Lassis M, Laurent-Matha V, Prébois C, Rochefort H, Vignon F. Cathepsin D: newly discovered functions of a long-standing aspartic protease in cancer and apoptosis. Cancer Lett. 2006;237:167–179.
    1. Hobbs CA, Gilmour SK. Role of polyamines in the regulation of chromatin acetylation. In: Wang JY, Casero RA Jr, editors. Polyamine Cell Signalling: Physiology, Pharmacology, and Cancer Research. Humana Press Inc; 2006. pp. 75–89.
    1. Hobbs C. A., Paul B. A., Gilmour S. K. Deregulation of polyamine biosynthesis alters intrinsic histone acetyltransferase and deacetylase activities in murine skin and tumors. Cancer Res. 2002;62:67–74.
    1. Handa AK, Mattoo AK. Differential and functional interactions emphasize the multiple roles of polyamines in plants. Plant Physiol Biochem. 2010;48:540–546.
    1. Landau G, Bercovich Z, Park MH, Kahana C. The role of polyamines in supporting growth of mammalian cells is mediated through their requirement for translation initiation and elongation. J Biol Chem. 2010;285:12474–12481.
    1. Christian BE, Haque ME, Spremulli LL. The effect of spermine on the initiation of mitochondrial protein synthesis. Biochem Biophys Res Comm. 2010;391:942–946.
    1. Chen T, Shen L, Yu J, Wan H, Guo A, Chen J, Long Y, Zhao J, Pei G. Rapamycin and other longevity-promoting compounds enhance the generation of mouse induced pluripotent stem cells. Aging Cell. 2011 DOI: 10.1111/j.1474-9726.2011.00722.x.
    1. Levine B, Kroemer G. Autophagy in the pathogenesis of disease. Cell. 2008;132:27–42.
    1. Mizushima N, Levine B, Cuervo AM, Klionsky DJ. Autophagy fights disease through cellular self-digestion. Nature. 2008;451:1069–1075.
    1. Fleming A, Noda T, Yoshimori T, Rubinsztein DC. Chemical modulators of autophagy as biological probes and potential therapeutics. Nat Chem Biol. 2011;7:9–17.
    1. Madeo F, Tavernarakis N, Kroemer G. Can autophagy promote longevity? Nat Cell Biol. 2010;12:842–846.
    1. Markaki M, Tavernarakis N. The role of autophagy in genetic pathways influencing ageing. Biogerontol. 2011 DOI: 10.1007/s10522-011-9324-9.
    1. Morselli E, Galluzzi L, Kepp O, Criollo A, Maiuri MC, Tavernarakis N, Madeo F, Kroemer G. Autophagy mediates pharmacological lifespan extension by spermidine and resveratrol. Aging. 2009;1:961–970.
    1. Madeo F, Eisenberg T, Büttner S, Ruckenstuhl C, Kroemer G. Spermidine: a novel autophagy inducer and longevity elixir. Autophagy. 2010;6:160–162.
    1. Morselli E, Mariño G, Bennetzen MV, Eisenberg T, Megalou E, Schroeder S, Cabrera S, Bénit P, Rustin P, Criollo A, Kepp O, Galluzzi L, Shen S, et al. Spermidine and resveratrol induce autophagy by distinct pathways converging on the acetylproteome. J Cell Biol. 2011;192:615–629.
    1. St-Denis NA, Litchfield DW. From birth to death: the role of protein kinase CK2 in the regulation of cell proliferation and survival. Cell Mol Life Sci. 2009;66:1817–1829.
    1. Stark F, Pfannstiel J, Klaiber I, Raabe T. Protein kinase CK2 links polyamine metabolism to MAPK signaling in Drosophila. Cell Signal. 2011 DOI: 10.1016/j.cellsig.2011.01.013.
    1. Niefind K, Raaf J, Issinger OG. Protein kinase CK2 in health and disease: Protein kinase CK2: from structures to insights. Cell Mol Life Sci. 2009;66:1800–1816.
    1. Shi C, Welsh PA, Sass-Kuhm S, Wang X, McCloskey DE, Pegg AE, Feith DJ. Characterization of transgenic mice with overexpression of spermidine synthase. Amino acids. 2011 DOI: 10.1007/s00726-011-1028-6.
    1. Sharp ZD, Richardson A. Aging and cancer: can mTOR inhibitors kill two birds with one drug? Targ Oncol. 2011 DOI 10.1007/s11523-011-0168-7.
    1. Blagosklonny MV. Rapamycin and quasi-programmed aging: four years later. Cell Cycle. 2010;9:1859–1862.

Source: PubMed

3
구독하다