Polyamines and Their Metabolism: From the Maintenance of Physiological Homeostasis to the Mediation of Disease

The polyamines spermidine and spermine are positively charged aliphatic molecules. They are critical in the regulation of nucleic acid and protein structures, protein synthesis, protein and nucleic acid interactions, oxidative balance, and cell proliferation. Cellular polyamine levels are tightly controlled through their import, export, de novo synthesis, and catabolism. Enzymes and enzymatic cascades involved in polyamine metabolism have been well characterized. This knowledge has been used for the development of novel compounds for research and medical applications. Furthermore, studies have shown that disturbances in polyamine levels and their metabolic pathways, as a result of spontaneous mutations in patients, genetic engineering in mice or experimentally induced injuries in rodents, are associated with multiple maladaptive changes. The adverse effects of altered polyamine metabolism have also been demonstrated in in vitro models. These observations highlight the important role these molecules and their metabolism play in the maintenance of physiological normalcy and the mediation of injury. This review will attempt to cover the extensive and diverse knowledge of the biological role of polyamines and their metabolism in the maintenance of physiological homeostasis and the mediation of tissue injury.

[1]  T. Andl,et al.  ATP13A3 facilitates polyamine transport in human pancreatic cancer cells , 2022, Scientific Reports.

[2]  L. Pellerin,et al.  The eukaryotic initiation factor 5A (eIF5A1), the molecule, mechanisms and recent insights into the pathophysiological roles , 2021, Cell & bioscience.

[3]  M. Marcoli,et al.  Reactive Astrocytosis in a Mouse Model of Chronic Polyamine Catabolism Activation , 2021, Biomolecules.

[4]  S. Rajasekaran,et al.  Repurposing eflornithine to treat a patient with a rare ODC1 gain-of-function variant disease , 2021, eLife.

[5]  W. Chung,et al.  Post-translational formation of hypusine in eIF5A: implications in human neurodevelopment , 2021, Amino Acids.

[6]  J. Cleveland,et al.  Polyamine Homeostasis in Development and Disease , 2021, Medical sciences.

[7]  R. Stallings,et al.  A G316A Polymorphism in the Ornithine Decarboxylase Gene Promoter Modulates MYCN-Driven Childhood Neuroblastoma , 2021, Cancers.

[8]  S. Rajasekaran,et al.  Emerging Role of ODC1 in Neurodevelopmental Disorders and Brain Development , 2021, Genes.

[9]  V. Baekelandt,et al.  ATP13A3 is a major component of the enigmatic mammalian polyamine transport system , 2020, The Journal of biological chemistry.

[10]  J. Cleveland,et al.  Ablation of polyamine catabolic enzymes provokes Purkinje cell damage, neuroinflammation, and severe ataxia , 2020, Journal of neuroinflammation.

[11]  Kristie L. Rose,et al.  Spermine Oxidase Mediates Helicobacter pylori-induced Gastric Inflammation, DNA Damage, and Carcinogenic Signaling , 2020, Oncogene.

[12]  V. Baekelandt,et al.  ATP13A2 deficiency disrupts lysosomal polyamine export , 2020, Nature.

[13]  Y. Moriyama,et al.  Vesicular polyamine transporter as a novel player in amine-mediated chemical transmission. , 2020, Biochimica et biophysica acta. Biomembranes.

[14]  M. Soleimani,et al.  Polyamine Catabolism in Acute Kidney Injury , 2019, International journal of molecular sciences.

[15]  M. Marcoli,et al.  Epileptic seizures and oxidative stress in a mouse model over-expressing spermine oxidase , 2019, Amino Acids.

[16]  Teresa L. Mastracci,et al.  Recessive Rare Variants in Deoxyhypusine Synthase, an Enzyme Involved in the Synthesis of Hypusine, Are Associated with a Neurodevelopmental Disorder. , 2019, American journal of human genetics.

[17]  K. Kashiwagi,et al.  The functional role of polyamines in eukaryotic cells. , 2019, The international journal of biochemistry & cell biology.

[18]  Prahalathan Pichavaram,et al.  Targeting Polyamine Oxidase to Prevent Excitotoxicity-Induced Retinal Neurodegeneration , 2019, Front. Neurosci..

[19]  R. Deberardinis,et al.  Gain‐of‐function variants in the ODC1 gene cause a syndromic neurodevelopmental disorder associated with macrocephaly, alopecia, dysmorphic features, and neuroimaging abnormalities , 2018, American journal of medical genetics. Part A.

[20]  C. Schwartz,et al.  Polyamine Homeostasis in Snyder-Robinson Syndrome , 2018, Medical sciences.

[21]  A. Kishore,et al.  Spermine protects alpha-synuclein expressing dopaminergic neurons from manganese-induced degeneration , 2018, Cell Biology and Toxicology.

[22]  D. Bowie Polyamine-mediated channel block of ionotropic glutamate receptors and its regulation by auxiliary proteins , 2018, The Journal of Biological Chemistry.

[23]  P. Woster,et al.  Polyamine catabolism and oxidative damage , 2018, The Journal of Biological Chemistry.

[24]  C. Nichols,et al.  Polyamines and potassium channels: A 25-year romance , 2018, The Journal of Biological Chemistry.

[25]  A. Rozov,et al.  The Role of Polyamine-Dependent Facilitation of Calcium Permeable AMPARs in Short-Term Synaptic Enhancement , 2018, Front. Cell. Neurosci..

[26]  U. Mabalirajan,et al.  Reduction in polyamine catabolism leads to spermine‐mediated airway epithelial injury and induces asthma features , 2018, Allergy.

[27]  M. Park,et al.  Hypusine, a polyamine-derived amino acid critical for eukaryotic translation , 2018, The Journal of Biological Chemistry.

[28]  S. Rajasekaran,et al.  Novel de novo pathogenic variant in the ODC1 gene in a girl with developmental delay, alopecia, and dysmorphic features , 2018, American journal of medical genetics. Part A.

[29]  A. Pegg,et al.  Polyamine metabolism and cancer: treatments, challenges and opportunities , 2018, Nature Reviews Cancer.

[30]  D. Shangguan,et al.  Oxidative degradation of polyamines by serum supplement causes cytotoxicity on cultured cells , 2018, Scientific Reports.

[31]  Guido Kroemer,et al.  Spermidine in health and disease , 2018, Science.

[32]  Takashi Hato,et al.  Endotoxin Preconditioning Reprograms S1 Tubules and Macrophages to Protect the Kidney. , 2017, Journal of the American Society of Nephrology : JASN.

[33]  M. Marcoli,et al.  Glutamate Excitotoxicity Linked to Spermine Oxidase Overexpression , 2018, Molecular Neurobiology.

[34]  A. Kanda,et al.  Soluble Vascular Adhesion Protein-1 Mediates Spermine Oxidation as Semicarbazide-Sensitive Amine Oxidase: Possible Role in Proliferative Diabetic Retinopathy , 2017, Current eye research.

[35]  Mark A. Hall,et al.  Activation of endoplasmic reticulum stress response by enhanced polyamine catabolism is important in the mediation of cisplatin-induced acute kidney injury , 2017, PloS one.

[36]  Jinu Kim Spermidine is protective against kidney ischemia and reperfusion injury through inhibiting DNA nitration and PARP1 activation , 2017, Anatomy & cell biology.

[37]  Yulong Yin,et al.  Polyamines: therapeutic perspectives in oxidative stress and inflammatory diseases , 2017, Amino Acids.

[38]  Steve D. M. Brown,et al.  Disease Model Discovery from 3,328 Gene Knockouts by The International Mouse Phenotyping Consortium , 2017, Nature Genetics.

[39]  Xiaoxiang Zheng,et al.  Induction of autophagy by spermidine is neuroprotective via inhibition of caspase 3-mediated Beclin 1 cleavage , 2017, Cell Death & Disease.

[40]  N. Melis,et al.  Targeting eIF5A Hypusination Prevents Anoxic Cell Death through Mitochondrial Silencing and Improves Kidney Transplant Outcome. , 2017, Journal of the American Society of Nephrology : JASN.

[41]  Stephan J Sigrist,et al.  Cardioprotection and lifespan extension by the natural polyamine spermidine , 2016, Nature Medicine.

[42]  W. Gu,et al.  Activation of SAT1 engages polyamine metabolism with p53-mediated ferroptotic responses , 2016, Proceedings of the National Academy of Sciences.

[43]  Haifeng Cheng,et al.  Spermine ameliorates ischemia/reperfusion injury in cardiomyocytes via regulation of autophagy. , 2016, American journal of translational research.

[44]  R. Lucas,et al.  Treatment with polyamine oxidase inhibitor reduces microglial activation and limits vascular injury in ischemic retinopathy. , 2016, Biochimica et biophysica acta.

[45]  Anatoli Ender,et al.  Spermidine Suppresses Age-Associated Memory Impairment by Preventing Adverse Increase of Presynaptic Active Zone Size and Release , 2016, PLoS biology.

[46]  W. Cao,et al.  Spermidine alleviates experimental autoimmune encephalomyelitis through inducing inhibitory macrophages , 2016, Cell Death and Differentiation.

[47]  A. Mandal,et al.  Global quantitative proteomics reveal up-regulation of endoplasmic reticulum stress response proteins upon depletion of eIF5A in HeLa cells , 2016, Scientific Reports.

[48]  L. Bravo,et al.  Epigenetic silencing of miR-124 prevents spermine oxidase regulation: Implications for Helicobacter pylori-induced gastric cancer , 2016, Oncogene.

[49]  Kate Campbell,et al.  Remaining Mysteries of Molecular Biology: The Role of Polyamines in the Cell. , 2015, Journal of molecular biology.

[50]  K. Kaibuchi,et al.  Extracellular and Intracellular Signaling for Neuronal Polarity. , 2015, Physiological reviews.

[51]  A. Mandal,et al.  Depletion of the polyamines spermidine and spermine by overexpression of spermidine/spermine N¹-acetyltransferase 1 (SAT1) leads to mitochondria-mediated apoptosis in mammalian cells. , 2015, The Biochemical journal.

[52]  T. A. Nagy,et al.  Increased Helicobacter pylori-associated gastric cancer risk in the Andean region of Colombia is mediated by spermine oxidase , 2014, Oncogene.

[53]  K. Khoo,et al.  Uncovering protein polyamination by the spermine-specific antiserum and mass spectrometric analysis , 2015, Amino Acids.

[54]  T. Murray-Stewart,et al.  Proximal Tubule Epithelial Cell Specific Ablation of the Spermidine/Spermine N1-Acetyltransferase Gene Reduces the Severity of Renal Ischemia/Reperfusion Injury , 2014, PloS one.

[55]  Nektarios Tavernarakis,et al.  Spermidine protects against α-synuclein neurotoxicity , 2014, Cell cycle.

[56]  M. Hiasa,et al.  Identification of a mammalian vesicular polyamine transporter , 2014, Scientific Reports.

[57]  Victoria A. Baronas,et al.  Inward rectifiers and their regulation by endogenous polyamines , 2014, Front. Physiol..

[58]  Terry K. Smith,et al.  Spermidine Feeding Decreases Age-Related Locomotor Activity Loss and Induces Changes in Lipid Composition , 2014, PloS one.

[59]  A. Pegg Toxicity of polyamines and their metabolic products. , 2013, Chemical research in toxicology.

[60]  P. Woster,et al.  Elevated ornithine decarboxylase activity promotes skin tumorigenesis by stimulating the recruitment of bulge stem cells but not via toxic polyamine catabolic metabolites , 2013, Amino Acids.

[61]  S. Merali,et al.  Modulation of polyamine metabolic flux in adipose tissue alters the accumulation of body fat by affecting glucose homeostasis , 2013, Amino Acids.

[62]  H. Wallace,et al.  Polyamines and membrane transporters , 2013, Amino Acids.

[63]  C. J. Woolstenhulme,et al.  eIF5A promotes translation of polyproline motifs. , 2013, Molecular cell.

[64]  M. Marcoli,et al.  A New Transgenic Mouse Model for Studying the Neurotoxicity of Spermine Oxidase Dosage in the Response to Excitotoxic Injury , 2013, Molecular Neurodegeneration.

[65]  W. Brooks Increased Polyamines Alter Chromatin and Stabilize Autoantigens in Autoimmune Diseases , 2013, Front. Immunol..

[66]  N. Chabot,et al.  Transglutaminase and Polyamination of Tubulin: Posttranslational Modification for Stabilizing Axonal Microtubules , 2013, Neuron.

[67]  H. E. Johansson,et al.  Depletion of cellular polyamines, spermidine and spermine, causes a total arrest in translation and growth in mammalian cells , 2013, Proceedings of the National Academy of Sciences.

[68]  T. Barrett,et al.  p53 mediates TNF-induced epithelial cell apoptosis in IBD. , 2012, The American journal of pathology.

[69]  G. Kroemer,et al.  Spermidine promotes stress resistance in Drosophila melanogaster through autophagy-dependent and -independent pathways , 2012, Cell Death and Disease.

[70]  L. Alhonen,et al.  Chemically induced oxidative stress increases polyamine levels by activating the transcription of ornithine decarboxylase and spermidine/spermine-N1-acetyltransferase in human hepatoma HUH7 cells. , 2012, Biochimie.

[71]  R. Schuster,et al.  Hepatocyte-specific ablation of spermine/spermidine-N1-acetyltransferase gene reduces the severity of CCl4-induced acute liver injury. , 2012, American journal of physiology. Gastrointestinal and liver physiology.

[72]  Y. Lyubchenko,et al.  Effect of Spermidine on Misfolding and Interactions of Alpha-Synuclein , 2012, PloS one.

[73]  S. Merali,et al.  Polyamine-Regulated Translation of Spermidine/Spermine-N1-Acetyltransferase , 2012, Molecular and Cellular Biology.

[74]  L. Shantz,et al.  Ornithine decarboxylase mRNA is stabilized in an mTORC1-dependent manner in Ras-transformed cells. , 2012, The Biochemical journal.

[75]  P. Woster,et al.  Polyamine catabolism contributes to enterotoxigenic Bacteroides fragilis-induced colon tumorigenesis , 2011, Proceedings of the National Academy of Sciences.

[76]  Laetitia Mony,et al.  Molecular basis of positive allosteric modulation of GluN2B NMDA receptors by polyamines , 2011, The EMBO journal.

[77]  Yalin Tang,et al.  A stabilizing and denaturing dual-effect for natural polyamines interacting with G-quadruplexes depending on concentration. , 2011, Biochimie.

[78]  F. Madeo,et al.  Polyamines in aging and disease , 2011, Aging.

[79]  Andrew T. Templin,et al.  Deoxyhypusine synthase haploinsufficiency attenuates acute cytokine signaling , 2011, Cell cycle.

[80]  W. Elmquist,et al.  OCT2 and MATE1 provide bidirectional agmatine transport. , 2011, Molecular pharmaceutics.

[81]  J. Tamargo,et al.  Flecainide increases Kir2.1 currents by interacting with cysteine 311, decreasing the polyamine-induced rectification , 2010, Proceedings of the National Academy of Sciences.

[82]  L. Alhonen,et al.  The role of spermidine/spermine N1-acetyltransferase in endotoxin-induced acute kidney injury. , 2010, American journal of physiology. Cell physiology.

[83]  C. Dinarello,et al.  The unique hypusine modification of eIF5A promotes islet beta cell inflammation and dysfunction in mice. , 2010, The Journal of clinical investigation.

[84]  P. Ivanov,et al.  eIF5A Promotes Translation Elongation, Polysome Disassembly and Stress Granule Assembly , 2010, PloS one.

[85]  K. Strauss,et al.  Polyamine catabolism is enhanced after traumatic brain injury. , 2010, Journal of neurotrauma.

[86]  C. Kahana,et al.  The Role of Polyamines in Supporting Growth of Mammalian Cells Is Mediated through Their Requirement for Translation Initiation and Elongation*♦ , 2010, The Journal of Biological Chemistry.

[87]  John F. Atkins,et al.  A profusion of upstream open reading frame mechanisms in polyamine-responsive translational regulation , 2009, Nucleic acids research.

[88]  K. Kashiwagi,et al.  Modulation of cellular function by polyamines. , 2010, The international journal of biochemistry & cell biology.

[89]  L. Alhonen,et al.  α-Methylspermidine protects against carbon tetrachloride-induced hepatic and pancreatic damage , 2010, Amino Acids.

[90]  Frank Sinner,et al.  Induction of autophagy by spermidine promotes longevity , 2009, Nature Cell Biology.

[91]  J. Bol,et al.  Transglutaminases and Transglutaminase‐Catalyzed Cross‐Links Colocalize with the Pathological Lesions in Alzheimer's Disease Brain , 2009, Brain Pathology.

[92]  J. Zell,et al.  Associations of a Polymorphism in the Ornithine Decarboxylase Gene with Colorectal Cancer Survival , 2009, Clinical Cancer Research.

[93]  A. Pegg,et al.  Polyamine catabolism and disease. , 2009, The Biochemical journal.

[94]  A. Pegg,et al.  Mouse models to investigate the function of spermine , 2009, Communicative & integrative biology.

[95]  R. Schuster,et al.  Ischemic and non-ischemic acute kidney injury cause hepatic damage. , 2009, Kidney international.

[96]  L. Alhonen,et al.  Spermidine/spermine-N1-acetyltransferase ablation protects against liver and kidney ischemia-reperfusion injury in mice. , 2009, American journal of physiology. Gastrointestinal and liver physiology.

[97]  J. Śanchez-Corona,et al.  A missense mutation, p.V132G, in the X‐linked spermine synthase gene (SMS) causes Snyder–Robinson syndrome , 2009, American journal of medical genetics. Part A.

[98]  I. Brown,et al.  Genetic polymorphism in ornithine decarboxylase and risk of breast cancer , 2009, Familial Cancer.

[99]  Mark A. Hall,et al.  Targeting ornithine decarboxylase impairs development of MYCN-amplified neuroblastoma. , 2009, Cancer research.

[100]  W. London,et al.  ODC1 is a critical determinant of MYCN oncogenesis and a therapeutic target in neuroblastoma. , 2008, Cancer research.

[101]  C. Dinarello,et al.  Eukaryotic translation initiation factor 5A small interference RNA-liposome complexes reduce inflammation and increase survival in murine models of severe sepsis and acute lung injury. , 2008, The Journal of infectious diseases.

[102]  C. Byus,et al.  Identification and Characterization of a Diamine Exporter in Colon Epithelial Cells* , 2008, Journal of Biological Chemistry.

[103]  J. F. Atkins,et al.  uORFs with unusual translational start codons autoregulate expression of eukaryotic ornithine decarboxylase homologs , 2008, Proceedings of the National Academy of Sciences.

[104]  Nathaniel S. Rial,et al.  Activated K‐RAS increases polyamine uptake in human colon cancer cells through modulation of caveolar endocytosis , 2008, Molecular carcinogenesis.

[105]  Gang Wei,et al.  Elevated ornithine decarboxylase levels activate ataxia telangiectasia mutated-DNA damage signaling in normal keratinocytes. , 2008, Cancer research.

[106]  M. Araie,et al.  Polyamine depletion induces G1 and S phase arrest in human retinoblastoma Y79 cells , 2008, Cancer Cell International.

[107]  M. Gorospe,et al.  Polyamines regulate the stability of activating transcription factor-2 mRNA through RNA-binding protein HuR in intestinal epithelial cells. , 2007, Molecular biology of the cell.

[108]  R. Minchin,et al.  Polyamine-dependent Regulation of Spermidine-Spermine N1-Acetyltransferase mRNA Translation* , 2007, Journal of Biological Chemistry.

[109]  C. Nichols,et al.  Polyamine Permeation and Rectification of Kir4.1 Channels , 2007, Channels.

[110]  J. Wang Polyamines and mRNA stability in regulation of intestinal mucosal growth , 2007, Amino Acids.

[111]  J. E. Rider,et al.  Spermine and spermidine mediate protection against oxidative damage caused by hydrogen peroxide , 2007, Amino Acids.

[112]  S. Merali,et al.  Genetically Altered Expression of Spermidine/Spermine N1-Acetyltransferase Affects Fat Metabolism in Mice via Acetyl-CoA* , 2007, Journal of Biological Chemistry.

[113]  P. Diegelman,et al.  Spermidine/spermine N1-acetyltransferase overexpression in kidney epithelial cells disrupts polyamine homeostasis, leads to DNA damage, and causes G2 arrest. , 2007, American journal of physiology. Cell physiology.

[114]  R. Casero,et al.  Tumor necrosis factor-alpha increases reactive oxygen species by inducing spermine oxidase in human lung epithelial cells: a potential mechanism for inflammation-induced carcinogenesis. , 2006, Cancer research.

[115]  Tiina Wahlfors,et al.  Polyamine-regulated unproductive splicing and translation of spermidine/spermine N1-acetyltransferase. , 2006, RNA.

[116]  K. Kashiwagi,et al.  Polyamines in renal failure , 2006, Amino Acids.

[117]  Maria C. Bewley,et al.  Structures of wild-type and mutant human spermidine/spermine N1-acetyltransferase, a potential therapeutic drug target , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[118]  M. Park The post-translational synthesis of a polyamine-derived amino acid, hypusine, in the eukaryotic translation initiation factor 5A (eIF5A). , 2006, Journal of biochemistry.

[119]  K. Kashiwagi,et al.  Polyamine Oxidase and Acrolein as Novel Biochemical Markers for Diagnosis of Cerebral Stroke , 2005, Stroke.

[120]  R. Peñafiel,et al.  Protecting or promoting effects of spermine on DNA strand breakage induced by iron or copper ions as a function of metal concentration. , 2005, Journal of inorganic biochemistry.

[121]  M. di Pietro,et al.  Nuclear aggregates of polyamines are supramolecular structures that play a crucial role in genomic DNA protection and conformation , 2005, The FEBS journal.

[122]  R. Dempsey,et al.  Effect of difluoromethylornithine on reperfusion injury after temporary middle cerebral artery occlusion , 2005, Journal of Clinical Neuroscience.

[123]  David L. Steffen,et al.  The DNA sequence of the human X chromosome , 2005, Nature.

[124]  P. Woster,et al.  Induction of human spermine oxidase SMO(PAOh1) is regulated at the levels of new mRNA synthesis, mRNA stabilization and newly synthesized protein. , 2005, The Biochemical journal.

[125]  Dimitri A Kramerov,et al.  Short retroposons in eukaryotic genomes. , 2005, International review of cytology.

[126]  Huifang M. Zhang,et al.  Polyamine-modulated expression of c-myc plays a critical role in stimulation of normal intestinal epithelial cell proliferation. , 2005, American journal of physiology. Cell physiology.

[127]  H. Rabb,et al.  Overexpression of SSAT in kidney cells recapitulates various phenotypic aspects of kidney ischemia-reperfusion injury. , 2004, Journal of the American Society of Nephrology : JASN.

[128]  H. Misra,et al.  Hydroxyl radical scavenging and singlet oxygen quenching properties of polyamines , 2004, Molecular and Cellular Biochemistry.

[129]  D. Jackson,et al.  Neuroprotective effects of spermine following hypoxia‐ischemia‐induced brain damage: A mechanistic study , 2004, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[130]  V. Subramaniam,et al.  NMR of α‐synuclein–polyamine complexes elucidates the mechanism and kinetics of induced aggregation , 2004, The EMBO journal.

[131]  K. Helzlsouer,et al.  Association among an ornithine decarboxylase polymorphism, androgen receptor gene (CAG) repeat length and prostate cancer risk. , 2004, The Journal of urology.

[132]  C. Skinner,et al.  X-linked spermine synthase gene (SMS) defect: the first polyamine deficiency syndrome , 2003, European Journal of Human Genetics.

[133]  C. W. Tabor,et al.  Spermidine but not spermine is essential for hypusine biosynthesis and growth in Saccharomyces cerevisiae: Spermine is converted to spermidine in vivo by the FMS1-amine oxidase , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[134]  D. Teti,et al.  Vitreous polyamines spermidine, putrescine, and spermine in human proliferative disorders of the retina , 2003, The British journal of ophthalmology.

[135]  D. Alberts,et al.  Pronounced reduction in adenoma recurrence associated with aspirin use and a polymorphism in the ornithine decarboxylase gene , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[136]  K. Kashiwagi,et al.  Increase in putrescine, amine oxidase, and acrolein in plasma of renal failure patients. , 2003, Biochemical and biophysical research communications.

[137]  H. Rabb,et al.  Expression of SSAT, a novel biomarker of tubular cell damage, increases in kidney ischemia-reperfusion injury. , 2003, American journal of physiology. Renal physiology.

[138]  V. Uversky,et al.  Polycation‐induced oligomerization and accelerated fibrillation of human α‐synuclein in vitro , 2003 .

[139]  D. Gründemann,et al.  Agmatine Is Efficiently Transported by Non-Neuronal Monoamine Transporters Extraneuronal Monoamine Transporter (EMT) and Organic Cation Transporter 2 (OCT2) , 2003, Journal of Pharmacology and Experimental Therapeutics.

[140]  V. Subramaniam,et al.  Cellular polyamines promote the aggregation of alpha-synuclein. , 2003, The Journal of biological chemistry.

[141]  K. Mita,et al.  Functional characterization of the human spermidine/spermine N(1)-acetyltransferase gene promoter. , 2002, Biochimica et biophysica acta.

[142]  P. Gregersen,et al.  Neuroprotection in cerebral ischemia by neutralization of 3-aminopropanal , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[143]  M. Batzer,et al.  Alu insertion polymorphisms for the study of human genomic diversity. , 2001, Genetics.

[144]  R. Dempsey,et al.  Ornithine Decarboxylase Knockdown Exacerbates Transient Focal Cerebral Ischemia-Induced Neuronal Damage in Rat Brain , 2001, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[145]  Y. Wang,et al.  Characterization of the interaction between the transcription factors human polyamine modulated factor (PMF-1) and NF-E2-related factor 2 (Nrf-2) in the transcriptional regulation of the spermidine/spermine N1-acetyltransferase (SSAT) gene. , 2001, The Biochemical journal.

[146]  S. Iwasaki,et al.  Polyamine cytotoxicity in the presence of bovine serum amine oxidase. , 2001, Biochemical and biophysical research communications.

[147]  B. Bass,et al.  Expression of the TGF-beta receptor gene and sensitivity to growth inhibition following polyamine depletion. , 2000, American journal of physiology. Cell physiology.

[148]  K. Kashiwagi,et al.  Polyamines: mysterious modulators of cellular functions. , 2000, Biochemical and biophysical research communications.

[149]  A. Gudkov,et al.  p53 is involved in tumor necrosis factor-α-induced apoptosis in the human prostatic carcinoma cell line LNCaP , 2000, Oncogene.

[150]  N. Sonenberg,et al.  A cell cycle-dependent internal ribosome entry site. , 2000, Molecular cell.

[151]  Y. Wang,et al.  Cloning and Characterization of Human Polyamine-modulated Factor-1, a Transcriptional Cofactor That Regulates the Transcription of the Spermidine/Spermine N 1-Acetyltransferase Gene* , 1999, The Journal of Biological Chemistry.

[152]  R. Kauppinen,et al.  Enhanced ornithine decarboxylase activity is associated with attenuated rate of damage evolution and reduction of infarct volume in transient middle cerebral artery occlusion in the rat 1 Published on the World Wide Web on 17 March 1999. 1 , 1999, Brain Research.

[153]  R. Dempsey,et al.  Effects of MDL 72527, a Specific Inhibitor of Polyamine Oxidase, on Brain Edema, Ischemic Injury Volume, and Tissue Polyamine Levels in Rats After Temporary Middle Cerebral After Occlusion , 1999, Journal of neurochemistry.

[154]  B. Nelkin,et al.  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 N 1-Acetyltransferase Gene Transcription* , 1998, The Journal of Biological Chemistry.

[155]  J. Zweier,et al.  The natural polyamine spermine functions directly as a free radical scavenger. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[156]  P. Gregersen,et al.  Cerebral Ischemia Enhances Polyamine Oxidation: Identification of Enzymatically Formed 3-Aminopropanal as an Endogenous Mediator of Neuronal and Glial Cell Death , 1998, The Journal of experimental medicine.

[157]  R. Kauppinen,et al.  Neuroprotective role of ornithine decarboxylase activation in transient focal cerebral ischaemia: a study using ornithine decarboxylase‐overexpressing transgenic rats , 1998, The European journal of neuroscience.

[158]  F. Lang,et al.  Electrogenic Properties and Substrate Specificity of the Polyspecific Rat Cation Transporter rOCT1* , 1996, The Journal of Biological Chemistry.

[159]  M. Mayer,et al.  Inward rectification of both AMPA and kainate subtype glutamate receptors generated by polyamine-mediated ion channel block , 1995, Neuron.

[160]  Rashid Hasan,et al.  Polyamine induced Z‐conformation of native calf thymus DNA , 1995, FEBS letters.

[161]  M. Krönke,et al.  TNF-induced activation of NF-kappa B. , 1995, Immunobiology.

[162]  S. Yuspa,et al.  Role of ornithine decarboxylase in epidermal tumorigenesis. , 1995, Cancer research.

[163]  J. F. Atkins,et al.  Autoregulatory frameshifting in decoding mammalian ornithine decarboxylase antizyme , 1995, Cell.

[164]  C. Robertson,et al.  DFMO Reduces Cortical Infarct Volume after Middle Cerebral Artery Occlusion in the Rat , 1993, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[165]  S. Matsufuji,et al.  Involvement of the proteasome and antizyme in ornithine decarboxylase degradation by a reticulocyte lysate. , 1993, The Biochemical journal.

[166]  J L Cleveland,et al.  The ornithine decarboxylase gene is a transcriptional target of c-Myc. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[167]  A. Mukherjee,et al.  Transglutaminase-catalyzed incorporation of polyamines into phospholipase A2. , 1993, Journal of biochemistry.

[168]  Hiroshi Kobayashi,et al.  Estimation of polyamine binding to macromolecules and ATP in bovine lymphocytes and rat liver. , 1991, The Journal of biological chemistry.

[169]  C. Hutchison,et al.  The DNA sequence of the human cytomegalovirus genome. , 1991, DNA sequence : the journal of DNA sequencing and mapping.

[170]  A. Pegg,et al.  High specific induction of spermidine/spermine N1-acetyltransferase in a human large cell lung carcinoma. , 1990, The Biochemical journal.

[171]  P. Sunkara,et al.  Ornithine decarboxylase induction and polyamine biosynthesis are required for the growth of interleukin-2- and interleukin-3-dependent cell lines. , 1986, Cellular immunology.

[172]  C. W. Tabor,et al.  Polyamines in microorganisms , 1985 .

[173]  P. McCann,et al.  Polyamine metabolism and function. , 1982, The American journal of physiology.

[174]  M. H. Park,et al.  Identification of hypusine, an unusual amino acid, in a protein from human lymphocytes and of spermidine as its biosynthetic precursor. , 1981, Proceedings of the National Academy of Sciences of the United States of America.

[175]  D. L. Dewey,et al.  Evidence for serum binding of oxidized spermine and its potent G1-phase inhibition of cell proliferation. , 1979, British Journal of Cancer.

[176]  D. Anderson,et al.  The actions of spermidine and spermine on the central nervous system , 1975, Neuropharmacology.

[177]  C. W. Tabor,et al.  IDENTIFICATION OF THE AMINOALDEHYDES PRODUCED BY THE OXIDATION OF SPERMINE AND SPERMIDINE WITH PURIFIED PLASMA AMINE OXIDASE. , 1964, The Journal of biological chemistry.

[178]  H. W. Dudley,et al.  The Chemical Constitution of Spermine: Structure and Synthesis. , 1926, The Biochemical journal.

[179]  Antoni van Leeuwenhoek Observationes D. Anthonii Lewenhoeck, de natis'e semine genitali animalculis , 1677, Philosophical Transactions of the Royal Society of London.