bims-polyam Biomed News
on Polyamines
Issue of 2021–09–26
eleven papers selected by
Sebastian J. Hofer, University of Graz



  1. Front Nutr. 2021 ;8 717343
      The human diet and dietary patterns are closely linked to the health status. High-calorie Western-style diets have increasingly come under scrutiny as their caloric load and composition contribute to the development of non-communicable diseases, such as diabetes, cancer, obesity, and cardiovascular disorders. On the other hand, calorie-reduced and health-promoting diets have shown promising results in maintaining health and reducing disease burden throughout aging. More recently, pharmacological Caloric Restriction Mimetics (CRMs) have gained interest of the public and scientific community as promising candidates that mimic some of the myriad of effects induced by caloric restriction. Importantly, many of the CRM candidates activate autophagy, prolong life- and healthspan in model organisms and ameliorate diverse disease symptoms without the need to cut calories. Among others, glycolytic inhibitors (e.g., D-allulose, D-glucosamine), hydroxycitric acid, NAD+ precursors, polyamines (e.g., spermidine), polyphenols (e.g., resveratrol, dimethoxychalcones, curcumin, EGCG, quercetin) and salicylic acid qualify as CRM candidates, which are naturally available via foods and beverages. However, it is yet unclear how these bioactive substances contribute to the benefits of healthy diets. In this review, we thus discuss dietary sources, availability and intake levels of dietary CRMs. Finally, since translational research on CRMs has entered the clinical stage, we provide a summary of their effects in clinical trials.
    Keywords:  caloric restriction mimetics; clinical trials; healthy diet; nutrition; polyamines; polyphenols; spermidine
    DOI:  https://doi.org/10.3389/fnut.2021.717343
  2. Biomed Res. 2021 ;42(5): 221-227
      Irregular light-dark cycles desynchronize the circadian clock via hormonal and neuronal pathways and increase the risk of various diseases. This study demonstrated that a single pulse of spermidine-a polyamine-strongly induced circadian phase advances in the presence or absence of dexamethasone (a synthetic glucocorticoid) in NIH3T3 cells transfected with the Bmal1 promotor-driven luciferase reporter gene. The spermidine-induced phase advances were 2-3 fold greater than were the dexamethasone-induced shifts. The phase resetting effect of spermidine occurred in a dose- and time-dependent manner and was not blocked by RU486, an antagonist of glucocorticoid receptors. Spermidine treatment modulated the expression of clock genes within 60 min, which was sooner than changes in the expression of autophagy-related genes. These findings suggested that spermidine is a potent modulator of the circadian phase, acting through glucocorticoid receptor-independent pathways, and may be useful for treating diseases related to circadian desynchrony.
    DOI:  https://doi.org/10.2220/biomedres.42.221
  3. Amino Acids. 2021 Sep 21.
      Among low molecular weight substances, polyamines (spermidine, spermine and their precursor putrescine) are present in eukaryotic cells at the mM level together with ATP and glutathione. It is expected therefore that polyamines play important roles in cell proliferation and viability. Polyamines mainly exist as a polyamine-RNA complex and regulate protein synthesis. It was found that polyamines enhance translation from inefficient mRNAs. The detailed mechanisms of polyamine stimulation of specific kinds of protein syntheses and the physiological functions of these proteins are described in this review. Spermine is metabolized into acrolein (CH2 = CH-CHO) and hydrogen peroxide (H2O2) by spermine oxidase. Although it is thought that cell damage is mainly caused by reactive oxygen species (O2-, H2O2, and •OH), it was found that acrolein is much more toxic than H2O2. Accordingly, the level of acrolein produced becomes a useful biomarker for several tissue-damage diseases like brain stroke. Thus, the mechanisms of cell toxicity caused by acrolein are described in this review.
    Keywords:  Acrolein; Brain infarction; Dementia; PC-Acro; Polyamines; Protein synthesis; RNA; Reactive oxygen species; Spermidine; Spermine
    DOI:  https://doi.org/10.1007/s00726-021-03073-w
  4. Biol Futur. 2020 Sep;71(3): 183-194
      Polyamines (PAs) are positively charged amines such as putrescine, spermidine and spermine that ubiquitously exist in all organisms. They have been considered as a new type of plant biostimulants, with pivotal roles in many physiological processes. Polyamine levels are controlled by intricate regulatory feedback mechanisms. PAs are directly or indirectly regulated through interaction with signaling metabolites (H202, NO), aminobutyric acid (GABA), phytohormones (abscisic acid, gibberellins, ethylene, cytokinins, auxin, jasmonic acid and brassinosteroids) and nitrogen metabolism (maintaining the balance of C:N in plants). Exogenous applications of PAs enhance the stress resistance, flowering and fruit set, synthesis of bioactive compounds and extension of agricultural crops shelf life. Up-regulation of PAs biosynthesis by genetic manipulation can be a novel strategy to increase the productivity of agricultural crops. Recently, the role of PAs in symbiosis relationships between plants and beneficial microorganisms has been confirmed. PA metabolism has also been targeted to design new harmless fungicides.
    Keywords:  Biomarker; Fungicide; Polyamines; Shelf life; Stress resistance
    DOI:  https://doi.org/10.1007/s42977-020-00027-3
  5. J Biol Chem. 2021 Sep 21. pii: S0021-9258(21)01022-X. [Epub ahead of print] 101219
      Polyamines are fundamental molecules of life, and their deep evolutionary history is reflected in extensive biosynthetic diversification. The polyamines putrescine, agmatine and cadaverine, are produced by pyridoxal 5'-phosphate-dependent L-ornithine, L-arginine and L-lysine decarboxylases (ODC, ADC, LDC), respectively, from both the alanine racemase (AR) and aspartate aminotransferase (AAT) folds. Two homologous forms of AAT-fold decarboxylase are present in bacteria: an ancestral form and a derived, acid-inducible extended form containing an N-terminal fusion to the receiver-like domain of a bacterial response regulator. Only ADC was known from the ancestral form, and limited to the Firmicutes phylum, whereas extended forms of ADC, ODC and LDC are present in Proteobacteria and Firmicutes. Here, we report the discovery of ancestral form ODC, LDC, and bifunctional O/LDC, and extend the phylogenetic diversity of functionally characterized ancestral ADC, ODC and LDC to include phyla Fusobacteria, Caldiserica, Nitrospirae and Euryarchaeota. Using purified recombinant enzymes, we show that these ancestral forms have a nascent ability to decarboxylate kinetically less preferred amino acid substrates with low efficiency, and that product inhibition primarily affects preferred substrates. We also note a correlation between the presence of ancestral ODC and ornithine/arginine auxotrophy, and link this with a known symbiotic dependence on exogenous ornithine produced by species using the arginine deiminase system. Finally, we show that ADC, ODC and LDC activities emerged independently, in parallel, in the homologous AAT-fold ancestral and extended forms. The emergence of the same ODC, ADC, and LDC activities in the non-homologous AR-fold, suggests that polyamine biosynthesis may be inevitable.
    Keywords:  agmatine; arginine; cadaverine; decarboxylase; lysine; ornithine; polyamine; putrescine
    DOI:  https://doi.org/10.1016/j.jbc.2021.101219
  6. Biol Futur. 2019 Jan;70(1): 71-78
       INTRODUCTION: Drought is a major environmental factor that limits crops productivity. To cope with the adverse effects of drought, plants have evolved various adaptive mechanisms, such as accumulation of osmolytes. Polyamines (PAs) play an important role in the plant growth and development and response to abiotic stresses. This experiment was conducted to investigate the role of exogenous PAs on drought tolerance of mung bean.
    METHODS: Mung bean seeds were soaked in 0 or 100 uM putrescine (Put), spermidine (Spd), spermine (Spm), or their mixture for 10 hr. Then, treated seeds were sown in the field and were exposed to drought stress condition.
    RESULTS: The growth attributes including shoot length, biomass, leaf area index (LAI), and grain yield markedly reduced due to drought stress. Drought stress also decreased soluble protein content, relative water content (RWC), chlorophyll value, stomatal conductance (gs), and net photosynthetic rate (PN) but increased malondialdehyde (MDA), total soluble sugars (TSS), and proline contents. Nonetheless, seed priming with the mixture of PAs alleviated adverse effects of drought stress and improved all growth attributes. Exogenous application of PAs also increased soluble protein content, RWC, chlorophyll value, PN, and more increased TSS and proline contents but decreased gs and MDA level.
    DISCUSSION: These results indicated that seed treatment with PAs especially combined treatment of Put + Spd + Spm could enhance drought tolerance of mung bean plants through the accumulation of osmoprotectants, improving water status, chlorophyll value, and PN as well as reduction of oxidative damage.
    Keywords:  putrescine; seed priming; spermidine; spermine; water stress
    DOI:  https://doi.org/10.1556/019.70.2019.09
  7. Commun Biol. 2021 Sep 22. 4(1): 1114
      Antimicrobial resistance genes, including multidrug efflux pumps, evolved long before the ubiquitous use of antimicrobials in medicine and infection control. Multidrug efflux pumps often transport metabolites, signals and host-derived molecules in addition to antibiotics or biocides. Understanding their ancestral physiological roles could inform the development of strategies to subvert their activity. In this study, we investigated the response of Acinetobacter baumannii to polyamines, a widespread, abundant class of amino acid-derived metabolites, which led us to identify long-chain polyamines as natural substrates of the disinfectant efflux pump AmvA. Loss of amvA dramatically reduced tolerance to long-chain polyamines, and these molecules induce expression of amvA through binding to its cognate regulator AmvR. A second clinically-important efflux pump, AdeABC, also contributed to polyamine tolerance. Our results suggest that the disinfectant resistance capability that allows A. baumannii to survive in hospitals may have evolutionary origins in the transport of polyamine metabolites.
    DOI:  https://doi.org/10.1038/s42003-021-02629-6
  8. Biol Futur. 2020 Sep;71(3): 313-321
      Water deficit is one of the most limiting factors for plant growth and production. Polyamines are osmo-active compounds and have important roles in plant resistance to water limitation. A pot experiment was undertaken in a greenhouse as factorial based on complete randomized block design with three replications to assess the physiological and biochemical responses of safflower to different levels of water supply (100% and 40% field capacity) and spermine (0, 40 and 60 µM). Ascorbate peroxidase and peroxidase activities (POX), malondialdehyde (MDA), hydrogen peroxide (H2O2), anthocyanins, soluble protein, soluble sugars and proline contents in shoots increased, while total phenols, flavonoids, and photosynthetic pigments significantly decreased due to water deficit. Foliar spray of spermine mitigated the adverse effects of water deficit by increasing the catalase, superoxide dismutase, POX activities, soluble proteins and photosynthetic pigments, and by decreasing MDA and H2O2 contents. Spermine could, therefore, play an important role in protecting photosynthetic system and cellular membranes during drought stress in safflower.
    Keywords:  Antioxidants; Osmolytes; Safflower; Spermine; Water limitation
    DOI:  https://doi.org/10.1007/s42977-020-00039-z
  9. J Clin Endocrinol Metab. 2021 Sep 20. pii: dgab683. [Epub ahead of print]
      
    Keywords:  MEN1; Men1 fl/flPdx1-Cre Tg mice; dpNETs; polyamines
    DOI:  https://doi.org/10.1210/clinem/dgab683
  10. Res Microbiol. 2021 Sep 17. pii: S0923-2508(21)00095-4. [Epub ahead of print] 103881
      Some bacterial stress responses are involved in survival under antibiotic treatment and contribute to less susceptible microbial forms selection. Here, we tested the role of cadaverine, one of the biogenic polyamines considered as universal adaptogens, in the processes. The expression of ldcC and cadA genes, encoding cadaverine-producing lysine decarboxylase, increased in Escherichia coli cells exposed to β-lactams and fluoroquinolones but not aminoglycosides. The transcriptional regulators RpoS and SoxS controlled the expression of ldcC and cadA, respectively, in response to antibiotics. Exogenous cadaverine had little effect on E. coli antibiotic susceptibility, whereas non-antibiotic-induced endogenous cadaverine contributed to its tolerance to β-lactams, fluoroquinolones, and aminoglycosides. Antibiotic-induced cadaverine synthesis promoted bacterial survival under fluoroquinolone exposure, as well as could contribute to low-resistant bacterial forms development. Selection under the fluoroquinolone levofloxacin exposure toward bacteria with an increased ability to synthesize cadaverine and negative correlation between LdcC activity and fluoroquinolone susceptibility in the selected forms were demonstrated. The same correlation in a special group of low-level resistant clinical E. coli isolates was revealed. So, cadaverine biosynthesis appeared to be a significant player in decreased E. coli antibiotic susceptibility development.
    Keywords:  antibiotic tolerance; fluoroquinolone; lysine decarboxylase; polyamines
    DOI:  https://doi.org/10.1016/j.resmic.2021.103881
  11. Front Pharmacol. 2021 ;12 746910
      Hand-foot syndrome (HFS) is a common capecitabine-based chemotherapy-related adverse event (CRAE) in patients with colorectal cancer (CRC). It is of great significance to comprehensively identify susceptible factors for HFS, and further to elucidate the biomolecular mechanism of HFS susceptibility. We performed an untargeted multi-omics analysis integrating DNA methylation, transcriptome, and metabolome data of 63 Chinese CRC patients who had complete CRAE records during capecitabine-based chemotherapy. We found that the metabolome changes for each of matched plasma, urine, and normal colorectal tissue (CRT) in relation to HFS were characterized by chronic tissue damage, which was indicated by reduced nucleotide salvage, elevated spermine level, and increased production of endogenous cytotoxic metabolites. HFS-related transcriptome changes of CRT showed an overall suppressed inflammation profile but increased M2 macrophage polarization. HFS-related DNA methylation of CRT presented gene-specific hypermethylation on genes mainly for collagen formation. The hypermethylation was accumulated in the opensea and shore regions, which elicited a positive effect on gene expression. Additionally, we developed and validated models combining relevant biomarkers showing reasonably good discrimination performance with the area under the receiver operating characteristic curve values from 0.833 to 0.955. Our results demonstrated that the multi-omics variations associated with a profibrotic phenotype were closely related to HFS susceptibility. HFS-related biomolecular variations in CRT contributed more to the relevant biomolecular mechanism of HFS than in plasma and urine. Spermine-related DNA hypermethylation and elevated expression of genes for collagen formation were closely associated with HFS susceptibility. These findings provided new insights into the susceptible factors for chemotherapy-induced HFS, which can promote the implementation of individualized treatment against HFS.
    Keywords:  DNA methylation; adverse effects; chemotherapy; hand-foot syndrome; immune response; multi-omics; spermine; susceptible factors
    DOI:  https://doi.org/10.3389/fphar.2021.746910