bims-polyam Biomed News
on Polyamines
Issue of 2021–12–19
eight papers selected by
Sebastian J. Hofer, University of Graz



  1. Microbiology (Reading). 2021 Dec;167(12):
      Polyamines constitute a group of organic polycations positively charged at physiological pH. They are involved in a large variety of biological processes, including the protection against physiological stress. In this study, we show that the genome of Streptococcus agalactiae, a commensal bacterium of the intestine and the vagina and one of the most common agents responsible of neonate infections, does not encode proteins homologous to the specific enzymes involved in the known polyamine synthetic pathways. This lack of biosynthetic capability was verified experimentally by TLC analysis of the intracellular content of S. agalactiae grown in the absence of polyamines. However, similar analyses showed that the polyamines spermidine, spermine and putrescine can be imported from the growth media into the bacteria. We found that all strains of S. agalactiae possess the genes encoding the polyamine ABC transporter PotABCD. We demonstrated that these genes form an operon with folK, a gene involved in folate biosynthesis, murB, a gene involved in peptidoglycan biosynthesis, and with clc, a gene encoding a Cl-/H+ antiporter involved in resistance to acid stress in Escherichia coli. Transcription of the potABCD operon is induced by peroxide-induced oxidative stress but not by acidic stress. Spermidine and spermine were found to be inducers of potABCD transcription at pH 7.4 whereas putrescine induces this expression only during peroxide-induced oxidative stress. Using a deletion mutant of potABCD, we were nevertheless unable to associate phenotypic traits to the PotABCD transporter, probably due to the existence of one or more as yet identified transporters with a redundant action.
    Keywords:  ABC transporter; oxidative stress; polyamines
    DOI:  https://doi.org/10.1099/mic.0.001124
  2. Cell Mol Life Sci. 2021 Dec 16.
      Living organisms repeatedly encounter stressful events and apply various strategies to survive. Polyamines are omnipresent bioactive molecules with multiple functions. Their transient synthesis, inducible by numerous stressful stimuli, is termed the polyamine stress response. Animals developed evolutionarily conserved strategies to cope with stresses. The urea cycle is an ancient attribute that deals with ammonia excess in terrestrial species. Remarkably, most fish retain the urea cycle genes fully expressed during the early stages of development and silenced in adult animals. Environmental challenges instigate urea synthesis in fish despite substantial energetic costs, which poses the question of the urea cycle's evolutionary significance. Arginase plays a critical role in oxidative stress-dependent reactions being the final urea cycle enzyme. Its unique subcellular localization, high inducibility, and several regulation levels provide a supreme ability to control the polyamine synthesis rate. Notably, oxidative stress instigates the arginase-1 activity in mammals. Arginase is also dysregulated in aging organisms' brain and muscle tissues, indicating its role in the pathogenesis of age-associated diseases. We designed a study to investigate the levels of the urea cycle and polyamine synthesis-related enzymes in a fish model of acute hypoxia. We evidence synchronized elevation of arginase-2 and ornithine decarboxylase following oxidative stress in adult fish and aging animals signifying the specific function of arginase-2 in fish. Moreover, we demonstrate oxidative stress-associated polyamine synthesis' induction and urea cycle' arrest in adult fish. The subcellular arginase localization found in the fish seems to correspond to its possible evolutionary roles.
    Keywords:  Aging; Arginase; Norvaline; Oxidative stress; Polyamines; Urea cycle
    DOI:  https://doi.org/10.1007/s00018-021-04043-x
  3. Curr Diab Rep. 2021 Dec 13. 21(12): 52
       PURPOSE OF REVIEW: Insulin is at the heart of diabetes mellitus (DM). DM alters cardiac metabolism causing cardiomyopathy, ultimately leading to heart failure. Polyamines, organic compounds synthesized by cardiomyocytes, have an insulin-like activity and effect on glucose metabolism, making them metabolites of interest in the DM heart. This review sheds light on the disrupted microRNA network in the DM heart in relation to developing novel therapeutics targeting polyamine biosynthesis to prevent/mitigate diabetic cardiomyopathy.
    RECENT FINDINGS: Polyamines prevent DM-induced upregulation of glucose and ketone body levels similar to insulin. Polyamines also enhance mitochondrial respiration and thereby regulate all major metabolic pathways. Non-coding microRNAs regulate a majority of the biological pathways in our body by modulating gene expression via mRNA degradation or translational repression. However, the role of miRNA in polyamine biosynthesis in the DM heart remains unclear. This review discusses the regulation of polyamine synthesis and metabolism, and its impact on cardiac metabolism and circulating levels of glucose, insulin, and ketone bodies. We provide insights on potential roles of polyamines in diabetic cardiomyopathy and putative miRNAs that could regulate polyamine biosynthesis in the DM heart. Future studies will unravel the regulatory roles these miRNAs play in polyamine biosynthesis and will open new doors in the prevention/treatment of adverse cardiac remodeling in diabetic cardiomyopathy.
    Keywords:  Diabetes; Heart; Insulin; Ketone body; Methionine cycle; T1DM; T2DM; Urea cycle
    DOI:  https://doi.org/10.1007/s11892-021-01429-w
  4. Plant Physiol Biochem. 2021 Dec 11. pii: S0981-9428(21)00622-7. [Epub ahead of print]170 225-233
      Polyamines, due to their positive charges, bind to ROS Reactive oxygen species (ROS) thereby stabilizing the plasma membrane (PM). Drought is one of the main limiting factors affecting tea plant yield and quality. However, the effect of Spermidine (Spd) or Spermine (Spm) on membrane stability and fluidity in tea plants under drought stress is poorly understood. In this investigation, an exogenous supply of 1 mM Spd or Spm did not mitigate drought stress-induced damage, however, an exogenous supply of 0.2 mM Spd or Spm application significantly alleviated drought-induced damage in tea plants. To further illustrate the role of 0.2 mM Spd or Spm in maintaining membrane integrity and fluidity, the fatty acid percentage and PM H+-ATPase activity were analyzed. Spd and Spm application significantly increased PM H+-ATPase activity by 43.79% compared with that without the addition of polyamine under drought stress. In addition, exogenous application of Spd and Spm also significantly increased C18:3 by approximately 10%, hence alleviating drought-reduced fatty acid unsaturation. In contrast, Spd and Spm metabolic inhibitors dicyclohexylamine (DCHA) further impaired PM H+-ATPase activity and fatty acid desaturation under the drought + DCHA treatment compared with the drought treatment, respectively. Taken together, 0.2 mM Spd and Spm application significantly enhanced drought tolerance by increasing fatty acid unsaturation and maintaining PM H+-ATPase activity in tea plants. Therefore, foliar application of 0.2 mM Spd or Spm can be a potential foliar-spraying substances for improving tea drought tolerance.
    Keywords:  Drought stress; Fatty acid; Plasma membrane H(+)-ATPase; Polyamines; Tea plants
    DOI:  https://doi.org/10.1016/j.plaphy.2021.12.008
  5. J Biotechnol. 2021 Dec 13. pii: S0168-1656(21)00300-X. [Epub ahead of print]
      Polyamines are small organic and basic polycations that perform essential regulatory functions in all living organisms. Fluctuations in polyamine content have been observed to occur during growth, development and under stress conditions, implying that polyamines play pivotal roles in diverse cellular and physiological processes. To achieve polyamine homeostasis, the entire metabolic pathway is subjected to a fine-tuned regulation of its biosynthetic and catabolic genes and enzymes. In this review, we describe and discuss the most important mechanisms implicated in the translational and post-translational regulation of polyamine metabolic enzymes in plants. At the translational level, we emphasize the role of polyamines in the modulation of upstream open reading frame (uORF) activities that control the translation of polyamine biosynthetic and catabolic mRNAs. At the post-translational level, different aspects of the regulation of polyamine metabolic proteins are depicted, such as the proteolytic activation of enzyme precursors, the importance of dimerization in protein stability as well as in protein intracellular localization.
    Keywords:  PEST sequences; dimerization; polyamines; proteolytic cleavage, translational and post-translational regulation, uORF
    DOI:  https://doi.org/10.1016/j.jbiotec.2021.12.004
  6. AMB Express. 2021 Dec 15. 11(1): 168
      In the bio-based polymer industry, putrescine is in the spotlight for use as a material. We constructed strains of Escherichia coli to assess its putrescine production capabilities through the arginine decarboxylase pathway in batch fermentation. N-Acetylglutamate (ArgA) synthase is subjected to feedback inhibition by arginine. Therefore, the 19th amino acid residue, Tyr, of argA was substituted with Cys to desensitize the feedback inhibition of arginine, resulting in improved putrescine production. The inefficient initiation codon GTG of argA was substituted with the effective ATG codon, but its replacement did not affect putrescine production. The essential genes for the putrescine production pathway, speA and speB, were cloned into the same plasmid with argAATG Y19C to form an operon. These genes were introduced under different promoters; lacIp, lacIqp, lacIq1p, and T5p. Among these, the T5 promoter demonstrated the best putrescine production. In addition, disruption of the puuA gene encoding enzyme of the first step of putrescine degradation pathway increased the putrescine production. Of note, putrescine production was not affected by the disruption of patA, which encodes putrescine aminotransferase, the initial enzyme of another putrescine utilization pathway. We also report that the strain KT160, which has a genomic mutation of YifEQ100TAG, had the greatest putrescine production. At 48 h of batch fermentation, strain KT160 grown in terrific broth with 0.01 mM IPTG produced 19.8 mM of putrescine.
    Keywords:  Glutamate-putrescine ligase; Macrodomain Ori protein; N-acetylglutamate synthase; Terrific broth
    DOI:  https://doi.org/10.1186/s13568-021-01330-5
  7. Immunometabolism. 2022 ;pii: e220001. [Epub ahead of print]4(1):
      T cells rapidly convert their cellular metabolic requirements upon activation, switching to a highly glycolytic program to satisfy their increasingly complex energy needs. Fundamental metabolic differences have been established for the development of Foxp3+ T regulatory (Treg) cells versus TH17 cells, alterations of which can drive disease. TH17 cell dysregulation is a driver of autoimmunity and chronic inflammation, contributing to pathogenesis in diseases such as multiple sclerosis. A recent paper published in Cell by Wagner, et al. combined scRNA-seq and metabolic mapping data to interrogate potential metabolic modulators of TH17 cell pathogenicity. This Compass to TH17 cell metabolism highlights the polyamine pathway as a critical regulator of TH17/Treg cell function, signifying its potential as a therapeutic target.
    Keywords:  Foxp3; T regulatory; TH17 cell; arginine; glycolysis; inflammation; metabolism; polyamine
    DOI:  https://doi.org/10.20900/immunometab20220001
  8. Front Plant Sci. 2021 ;12 771464
      Changes in the chemical environment at the maturation stage in Pinus spp. somatic embryogenesis will be a determinant factor in the conversion of somatic embryos to plantlets. Furthermore, the study of biochemical and morphological aspects of the somatic embryos could enable the improvement of somatic embryogenesis in Pinus spp. In the present work, the influence of different amino acid combinations, carbohydrate sources, and concentrations at the maturation stage of Pinus radiata D. Don and Pinus halepensis Mill. was analyzed. In P. radiata, the maturation medium supplemented with 175 mM of sucrose and an increase in the amino acid mixture (1,100 mgL-1 of L-glutamine, 1,050 mgL-1 of L-asparagine, 350 mgL-1 of L-arginine, and 35 mgL-1 of L-proline) promoted bigger embryos, with a larger stem diameter and an increase in the number of roots in the germinated somatic embryos, improving the acclimatization success of this species. In P. halepensis, the maturation medium supplemented with 175 mM of maltose improved the germination of somatic embryos. The increase in the amount of amino acids in the maturation medium increased the levels of putrescine in the germinated somatic embryos of P. halepensis. We detected significant differences in the amounts of polyamines between somatic plantlets of P. radiata and P. halepensis; putrescine was less abundant in both species. For the first time, in P. radiata and P. halepensis somatic embryogenesis, we detected the presence of cadaverine, and its concentration changed according to the species.
    Keywords:  Pinus halepensis; Pinus radiata; amino acids; osmolality; sugars
    DOI:  https://doi.org/10.3389/fpls.2021.771464