bims-polyam Biomed News
on Polyamines
Issue of 2019‒04‒21
ten papers selected by
Alexander Ivanov
Engelhardt Institute of Molecular Biology


  1. Amino Acids. 2019 Apr 19.
    Soda K.
      The polyamines spermidine and spermine are synthesized in almost all organisms and are also contained in food. Polyamine synthesis decreases with aging, but no significant decrease in polyamine concentrations were found in organs, tissues, and blood of adult animals and humans. We found that healthy dietary patterns were associated with a preference for polyamine-rich foods, and first reported that increased polyamine intake extended the lifespan of mice and decreased the incidence of colon cancer induced by repeated administration of moderate amounts of a carcinogen. Recent investigations have revealed that changes in DNA methylation status play an important role in lifespan and aging-associated pathologies. The methylation of DNA is regulated by DNA methyltransferases in the presence of S-adenosylmethionine. Decarboxylated S-adenosylmethionine, converted from S-adenosylmethionine by S-adenosylmethionine decarboxylase, provides an aminopropyl group to synthesize spermine and spermidine and acts to inhibit DNMT activity. Long-term increased polyamine intake were shown to elevate blood spermine levels in mice and humans. In vitro studies demonstrated that spermine reversed changes induced by the inhibition of ornithine decarboxylase (e.g., increased decarboxylated S-adenosylmethionine, decreased DNA methyltransferase activity, increased aberrant DNA methylation), whose activity decreases with aging. Further, aged mice fed high-polyamine chow demonstrated suppression of aberrant DNA methylation and a consequent increase in protein levels of lymphocyte function-associated antigen 1, which plays a pivotal role on inflammatory process. This review discusses the relation between polyamine metabolism and DNA methylation, as well as the biological mechanism of lifespan extension induced by increased polyamine intake.
    Keywords:  Aging-associated diseases; Gene methylation; Lifespan; Senescence; Spermidine; Spermine
    DOI:  https://doi.org/10.1007/s00726-019-02733-2
  2. Amino Acids. 2019 Apr 16.
    Perdeh J, Berioso B, Love Q, LoGiudice N, Le TL, Harrelson JP, Roberts SC.
      Polyamines are metabolites that play important roles in rapidly proliferating cells, and recent studies have highlighted their critical nature in Leishmania parasites. However, little is known about the function of polyamines in parasites. To address this question, we assessed the effect of polyamine depletion in Leishmania donovani mutants lacking ornithine decarboxylase (Δodc) or spermidine synthase (Δspdsyn). Intracellular putrescine levels depleted rapidly in Δodc mutants and accumulated in Δspdsyn mutants, while spermidine levels were maintained at low but stable levels in both cell lines. Putrescine depletion in the Δodc mutants led to cell rounding, immediate cessation of proliferation, and loss of viability, while putrescine-rich Δspdsyn mutants displayed an intermediate proliferation phenotype and were able to arrest in a quiescent-like state for 6 weeks. Supplementation of Δodc mutants with spermidine had little effect on cell proliferation and morphology but enabled parasites to persist for 14 weeks. Thus, putrescine is not only essential as precursor for spermidine formation but also critical for parasite proliferation, morphology, and viability.
    Keywords:  Gene deletion mutants; Leishmania; Polyamines; Proliferation; Putrescine; Viability
    DOI:  https://doi.org/10.1007/s00726-019-02736-z
  3. Kardiologiia. 2019 Apr 13. 59(3): 43-51
    Kuzmin VS, Egorov YV, Rozenshtraukh LV.
      Cytoplasmic polyamines (PA) are involved in control of many cellular functions and are well known as regulators of so called inward-rectifier potassium ion channels. Nevertheless, functional significance of extracellular PA in the heart is poorly elucidated. Aim of this study was to study effects of endogenous PA spermine in the ventricular myocardium. Effects of the extracellular spermine were investigated in isolated multicellular preparations of rabbit and rat ventricular myocardium. Langendorff-perfused  isolated rat and rabbit hearts were also used. Action potential (APs) duration and pattern of excitation in ventricular myocardium were estimated using standard microelectrode technique and optical mapping. Functional refractory periods were assessed in Langendorff perfused hearts with the help of programmedelectrical stimulation of the ventricle. In this study extracellular PA spermine (0.1-5 mM) induced shortening of the APs in multicellular preparations of rat ventricular myocardium registered using sharp microelectrode technique. However, spermine caused only weak effect in preparations of ventricular myocardium from rabbit heart: highest tested concentration of spermine (5 mM) induced 4.7 % APs shortening. Similarly, 0.1-1 mM of spermine was unable to alter substantially ventricular effective refractory periods in isolated perfused rabbit hearts. In two animal species tested (rat and rabbit) 0.1-1 mM of spermine failed to affect conduction velocity and activation pattern in ventricles of isolated Langendorff-perfused hearts under normoxia. However, in the rat no-flow model of ischemia-reperfusion extracellular spermine improved conduction of excitation in ventricles. Our results allow suggesting that extracellular spermine can prevent ischemia-induced proarrhythmic changes in ventricular myocardium probably due to reduction of calcium accumulation, but this effect is significant only when PA is applied in millimolar concentrations. Also, potential anti-ischemic effect of the PA may be species specific.
    DOI:  https://doi.org/10.18087/cardio.2019.3.10240
  4. Front Plant Sci. 2019 ;10 301
    Piñero MC, Porras ME, López-Marín J, Sánchez-Guerrero MC, Medrano E, Lorenzo P, Del Amor FM.
      The horticultural industry demands high-quality resources to achieve excellence in yield and optimal revenues. Nitrogen is a pivotal nutrient to accomplish these goals for plant growth and product quality. However, competition for water in semi-arid regions can force the use of brackish waters, which can impair N uptake. The lower N uptake can be due to several reasons, such as an antagonism between ions, an absence of ATP, and/or alteration of N metabolism. The effect of supplying N as NO 3 - alone or in combination with NH 4 + , coupled with low or high salinity (8 or 20 mM NaCl), has been studied in sweet pepper fruits (Capsicum annuum L. cv. Melchor). The application of NH 4 + at high salinity affected chromatic parameters (a∗, b∗, and C∗), while chlorophyll a and b levels declined and β-carotene increased. The concentrations of P, K, Ca, Mg, and Cu were reduced in the fruits of plants irrigated with NH 4 + . The concentration of Na was only reduced when NH 4 + was supplied. Likewise, the concentration of total phenolics was also reduced at high salinity. However, total protein was unaffected. The amino acid profile was altered by the supply of NH 4 + , which reduced the concentrations of histidine and phenylalanine. Moreover, the concentrations of putrescine and cadaverine were increased by NH 4 + at high salinity, whereas that of cadaverine was reduced by NH 4 + at low salinity. The observed changes in fruit quality triggered by salinity, under the conditions of this study, should be borne in mind for this crop with regard to the envisaged palliative effect of the supply of N- NH 4 + .
    Keywords:  Capsicum annuum L.; free amino acids; nitrogen; nutrients; polyamines; salinity
    DOI:  https://doi.org/10.3389/fpls.2019.00301
  5. Front Plant Sci. 2019 ;10 320
    Sekula B, Dauter Z.
      Plants are unique eukaryotes that can produce putrescine (PUT), a basic diamine, from arginine via a three-step pathway. This process starts with arginine decarboxylase that converts arginine to agmatine. Then, the consecutive action of two hydrolytic enzymes, agmatine iminohydrolase (AIH) and N-carbamoylputrescine amidohydrolase, ultimately produces PUT. An alternative route of PUT biosynthesis requires ornithine decarboxylase that catalyzes direct putrescine biosynthesis. However, some plant species lack this enzyme and rely only on agmatine pathway. The scope of this manuscript concerns the structural characterization of AIH from the model legume plant, Medicago truncatula. MtAIH is a homodimer built of two subunits with a characteristic propeller fold, where five αββαβ repeated units are arranged around the fivefold pseudosymmetry axis. Dimeric assembly of this plant AIH, formed by interactions of conserved structural elements from one repeat, is drastically different from that observed in dimeric bacterial AIHs. Additionally, the structural snapshot of MtAIH in complex with 6-aminohexanamide, the reaction product analog, presents the conformation of the enzyme during catalysis. Our structural results show that MtAIH undergoes significant structural rearrangements of the long loop, which closes a tunnel-shaped active site over the course of the catalytic event. This conformational change is also observed in AIH from Arabidopsis thaliana, indicating the importance of the closed conformation of the gate-keeping loop for the catalysis of plant AIHs.
    Keywords:  agmatine deiminase; beta/alpha propeller fold; guanidine-modifying enzymes; penteins; polyamine biosynthesis; putrescine
    DOI:  https://doi.org/10.3389/fpls.2019.00320
  6. Plants (Basel). 2019 Apr 15. pii: E99. [Epub ahead of print]8(4):
    Sagor GHM, Kusano T, Berberich T.
      Of the five polyamine oxidases in Arabidopsis thaliana, AtPAO5 has a substrate preference for the tetraamine thermospermine (T-Spm) which is converted to triamine spermidine (Spd) in a back-conversion reaction in vitro. A homologue of AtPAO5 from the lycophyte Selaginella lepidophylla (SelPAO5) back-converts T-Spm to the uncommon polyamine norspermidine (NorSpd) instead of Spd. An Atpao5 loss-of-function mutant shows a strong reduced growth phenotype when growing on a T-Spm containing medium. When SelPAO5 was expressed in the Atpao5 mutant, T-Spm level decreased to almost normal values of wild type plants, and NorSpd was produced. Furthermore the reduced growth phenotype was cured by the expression of SelPAO5. Thus, a NorSpd synthesis pathway by PAO reaction and T-Spm as substrate was demonstrated in planta and the assumption that a balanced T-Spm homeostasis is needed for normal growth was strengthened.
    Keywords:  Arabidopsis thaliana mutant; Selaginella lepidophylla; norspermidine; polyamine oxidase; thermospermine
    DOI:  https://doi.org/10.3390/plants8040099
  7. Dev Neurosci. 2019 Apr 17. 1-14
    Krystofova J, Pathipati P, Russ J, Sheldon A, Ferriero D.
      Brain damage after hypoxia-ischemia (HI) occurs in an age-dependent manner. Neuroprotective strategies assumed to be effective in adults might have deleterious effects in the immature brain. In order to create effective therapies, the complex pathophysiology of HI in the developing brain requires exploring new mechanisms. Critical determinants of neuronal survival after HI are the extent of vascular dysfunction, inflammation, and oxidative stress, followed later by tissue repair. The key enzyme of these processes in the human body is arginase (ARG) that acts via the bioavailability of nitric oxide, and the synthesis of polyamines and proline. ARG is expressed throughout the brain in different cells. However, little is known about the effect of ARG in pathophysiological states of the brain, especially hypoxia-ischemia. Here, we summarize the role of ARG during neurodevelopment as well as in various brain pathologies.
    Keywords:  Arginase; Hypoxia-ischemia; Neonatal brain; Neuroinflammation
    DOI:  https://doi.org/10.1159/000496467
  8. Phytopathology. 2019 Apr 16.
    Seifi HS, Zarei A, Hsiang T, Shelp B.
      Polyamines (PAs) are ubiquitous aliphatic amines that play important roles in growth, development and environmental stress responses in plants. In this study, we report that exogenous application of spermine (Spm) is effective in the induction of resistance to gray mold disease, which is caused by the necrotrophic fungal pathogen Botrytis cinerea, on tomato (Solanum lycopersicum L.), bean (Phaseolus vulgaris L.) and Arabidopsis thaliana [L.] Heynh. Transcriptomic analysis revealed a priming role for the Spm molecule in Arabidopsis, resulting in strong upregulation of several important defense-associated genes, particularly those involved in systemic-acquired resistance. Microscopic analysis confirmed that Spm application potentiates endogenous defense responses in tomato leaves through the generation of reactive oxygen species and the hypersensitive response, which effectively contained B. cinerea growth within the inoculated area. Moreover, co-application of Spm and salicylic acid resulted in a synergistic effect against the pathogen, leading to higher levels of resistance than those induced by separate applications of the two compounds. The Spm plus salicylic acid treatment also reduced infection in systemic, non-treated leaves of tomato plants. Our findings suggest that Spm, particularly when applied in combination with salicylic acid, functions as a potent plant defense activator that leads to effective local and systemic resistance against B. cinerea.
    Keywords:  Biochemistry and cell biology; Disease control and pest management
    DOI:  https://doi.org/10.1094/PHYTO-12-18-0470-R
  9. Photosynth Res. 2019 Apr 19.
    Wu X, Shu S, Wang Y, Yuan R, Guo S.
      When plants suffer from abiotic stresses, cyclic electron flow (CEF) is induced for photo-protection. Putrescine (Put), a primary polyamine in chloroplasts, plays a critical role in stress tolerance. However, the relationship between CEF and Put in chloroplasts for photo-protection is unknown. In this study, we investigated the role of Put-induced CEF for salt tolerance in cucumber plants (Cucumis sativus L). Treatment with 90 mM NaCl and/or Put did not influence the maximum photochemical efficiency of PSII (Fv/Fm), but the photoactivity of PSI was severely inhibited by NaCl. Salt stress induced a high level of CEF; moreover, plants treated with both NaCl and Put exhibited much higher CEF activity and ATP accumulation than those exhibited by single-salt-treated plants to provide an adequate ATP/NADPH ratio for plant growth. Furthermore, Put decreased the trans-membrane proton gradient (ΔpH), which was accompanied by reduced pH-dependent non-photochemical quenching (NPQ) and an increased the effective quantum yield of PSII (Y(II)). The ratio of NADP+/NADPH increased significantly with Put in salt-stressed leaves compared with the ratio in leaves treated with NaCl, indicating that Put relieved over-reduction pressure at the PSI acceptor side caused by salt stress. Collectively, our results suggest that exogenous Put creates an excellent condition for CEF promotion: a large amount of pmf is predominantly stored as Δψ, resulting in moderate lumen pH and low NPQ, while maintaining high rates of ATP synthesis (high pmf).
    Keywords:  Cucumber; Cyclic electron flow; Photoprotection; Putrescine; Salt stress
    DOI:  https://doi.org/10.1007/s11120-019-00631-y
  10. J Inherit Metab Dis. 2019 Apr 14.
    Häberle J, Burlina A, Chakrapani A, Dixon M, Karall D, Lindner M, Mandel H, Martinelli D, Pintos-Morell G, Santer R, Skouma A, Servais A, Tal G, Rubio V, Huemer M, Dionisi-Vici C.
      In 2012 we published guidelines summarizing and evaluating late 2011 evidence for diagnosis and therapy of urea cycle disorders (UCDs). With 1:35,000 estimated incidence, UCDs cause hyperammonemia of neonatal (~50%) or late onset that can lead to intellectual disability or death, even while effective therapies do exist. In the 7 years that have elapsed since the first guideline was published, abundant novel information has accumulated, experience on newborn screening for some UCDs has widened, a novel hyperammonemia-causing genetic disorder has been reported, glycerol phenylbutyrate has been introduced as a treatment, and novel promising therapeutic avenues (including gene therapy) have been opened. Several factors including the impact of the first edition of these guidelines (frequently read and quoted) may have increased awareness among health professionals and patient families. However, under-recognition and delayed diagnosis of UCDs still appear widespread. It was therefore necessary to revise the original guidelines to ensure an up-to-date frame of reference for professionals and patients as well as for awareness campaigns. This was accomplished by keeping the original spirit of providing a trans-European consensus based on robust evidence (scored with GRADE methodology), involving professionals on UCDs from nine countries in preparing this consensus. We believe this revised guideline, which has been reviewed by several societies that are involved in the management of UCDs, will have a positive impact on the outcomes of patients by establishing common standards, and spreading and harmonising good practices. It may also promote the identification of knowledge voids to be filled by future research. TAKE-HOME MESSAGE: This is the first revision of the urea cycle disorders guideline after extensive revision of the previous work from 2012, this time developed based on GRADE methodology. This article is protected by copyright. All rights reserved.
    Keywords:  GRADE; N-acetylglutamate synthase; UCD; Urea cycle disorders; ammonia; arginase 1; argininosuccinate lyase; argininosuccinate synthetase; carbamoylphosphate synthetase 1; guidelines; hyperammonemia; hyperornithinemia-hyperammonemia-homocitrullinuria syndrome; ornithine transcarbamylase
    DOI:  https://doi.org/10.1002/jimd.12100