bims-polyam Biomed News
on Polyamines
Issue of 2019‒12‒15
eleven papers selected by
Alexander Ivanov
Engelhardt Institute of Molecular Biology


  1. Surg Obes Relat Dis. 2019 Nov 02. pii: S1550-7289(19)31078-0. [Epub ahead of print]
    Ocaña-Wilhelmi L, Cardona F, Garrido-Sanchez L, Fernandez-Garcia D, Tinahones FJ, Ramos-Molina B.
      BACKGROUND: Recent works have reported that bariatric surgery has remarkable effects on the metabolome, which might be potentially associated to the metabolic improvement of this procedure in patients with obesity. Serum polyamines, metabolites derived from amino acid metabolism, have been recently related to the metabolic status in obese individuals. However, the impact of bariatric surgery on the circulating levels of polyamines remains elusive.OBJECTIVE: To evaluate the effect of bariatric surgery on serum polyamine levels and to evaluate the association of changes in these molecules with metabolic improvement in patients with morbid obesity.
    SETTING: Virgen de la Victoria University Hospital, Malaga, Spain.
    METHODS: This study included 32 morbidly obese patients (weight index ≥40 kg/m2) with metabolic syndrome, who underwent sleeve gastrectomy. Serum levels of polyamines (putrescine, spermidine, and spermine), acetylpolyamines, and polyamine-related amino acids (arginine and ornithine) were assessed at baseline and 6 months after bariatric surgery, and were analyzed in an ultraperformance liquid chromatography-mass spectrometry platform.
    RESULTS: Our metabolomic analysis revealed a significant rise in several metabolites related to the polyamine metabolism, such as putrescine and acetyl derivatives of spermidine and spermine in serum samples from morbidly obese patients after bariatric surgery. Changes in serum levels of both putrescine and acetylputrescine were associated to the resolution of metabolic syndrome after surgery.
    CONCLUSION: Our study indicates that bariatric surgery affects the serum polyamine pattern and the resolution of metabolic syndrome after bariatric surgery is associated to specific changes in the serum polyamine metabolome.
    Keywords:  Bariatric surgery; Metabolic syndrome; Metabolomics; Obesity; Polyamines
    DOI:  https://doi.org/10.1016/j.soard.2019.10.024
  2. Int J Mol Sci. 2019 Dec 11. pii: E6248. [Epub ahead of print]20(24):
    Muxel SM, Mamani-Huanca M, Aoki JI, Zampieri RA, Floeter-Winter LM, López-Gonzálvez Á, Barbas C.
      BACKGROUND: Leishmaniases are neglected tropical diseases that are caused by Leishmania, being endemic worldwide. L-arginine is an essential amino acid that is required for polyamines production on mammal cells. During Leishmania infection of macrophages, L-arginine is used by host and parasite arginase to produce polyamines, leading to parasite survival; or, by nitric oxide synthase 2 to produce nitric oxide leading to parasite killing. Here, we determined the metabolomic profile of BALB/c macrophages that were infected with L. amazonensis wild type or with L. amazonensis arginase knockout, correlating the regulation of L-arginine metabolism from both host and parasite.METHODS: The metabolites of infected macrophages were analyzed by capillary electrophoresis coupled with mass spectrometry (CE-MS). The metabolic fingerprints analysis provided the dual profile from the host and parasite.
    RESULTS: We observed increased levels of proline, glutamic acid, glutamine, L-arginine, ornithine, and putrescine in infected-L. amazonensis wild type macrophages, which indicated that this infection induces the polyamine production. Despite this, we observed reduced levels of ornithine, proline, and trypanothione in infected-L. amazonensis arginase knockout macrophages, indicating that this infection reduces the polyamine production.
    CONCLUSIONS: The metabolome fingerprint indicated that Leishmania infection alters the L-arginine/polyamines/trypanothione metabolism inside the host cell and the parasite arginase impacts on L-arginine metabolism and polyamine production, defining the infection fate.
    Keywords:  arginine; bone marrow-derived macrophages; metabolites; polyamines pathway
    DOI:  https://doi.org/10.3390/ijms20246248
  3. Front Plant Sci. 2019 ;10 1309
    Luo J, Wei B, Han J, Liao Y, Liu Y.
      The improvement of grain filling is the key issue for promoting wheat thousand grain weight and grain yield. The levels of polyamines (PAs) significantly affect grain filling in cereals, but the mechanism by which PAs affect grain filling in wheat is unclear. In the present study, six wheat cultivars whose grain filling differed were used, and their grain-filling characteristics and endogenous PA contents were measured. In addition, exogenous PAs were supplied during the wheat grain-filling period. The grain-filling characteristics, hormone levels, starch contents, and gene expression [based on RNA sequencing (RNA-seq)] in the grain were analyzed. The objective of the present study was to investigate the effects of PAs on grain filling in wheat. The results suggested that the direct synthetic pathway from putrescine (Put) to spermidine (Spd) in the grain was a key factor in promoting grain filling and thousand grain weight in wheat. Spd through regulates the grain-filling rate of inferior grain during the early grain-filling period to affecting the grain filling and thousand grain weight of wheat. The promotive effect of Spd on the grain filling of inferior wheat grain was notably related to carbohydrate metabolism in that grain. Spd significantly increased the zeatin (Z) + zeatin riboside (ZR) contents but reduced the ethylene (ETH) evolution rate in the inferior grain. In addition, Spd significantly increased the sucrose synthase (SS) and acid invertase (AI) activities in the inferior grain. These effects of Spd led to increased sucrose content in the inferior grain. These reasons might explain why Spd significantly promoted the filling and weight of inferior wheat grain.
    Keywords:  carbohydrate transport; grain filling; hormone; polyamine; wheat
    DOI:  https://doi.org/10.3389/fpls.2019.01309
  4. Comp Biochem Physiol A Mol Integr Physiol. 2019 Dec 05. pii: S1095-6433(19)30395-2. [Epub ahead of print] 110632
    Clark TC, Tinsley J, Sigholt T, Macqueen DJ, Martin SAM.
      Functional amino acids (FAA) regulate metabolic pathways directly linked to health, survival, growth and development. Arginine is a FAA with crucial roles in protein deposition and the immune response. In mammals, supplementation of arginine's precursor amino acid, citrulline, is known to increase circulating arginine to levels beyond direct arginine supplementation, however, citrulline supplementation is poorly studied in fish. To address this knowledge gap, we supplemented the diet of rainbow trout with arginine and its precursor amino acids, ornithine and citrulline, at 3 levels (0.5%, 1% and 2% of the total diet) during a 14-week experiment. We sampled fish at 3 h and 24 h post-feeding to investigate immediate and steady-state effects, respectively. There were no differences in fish growth for any of the diets across a range of indicators. In blood plasma, out of 26 amino acids detected, 11 and 6 displayed significant changes 24 h and 3 h post-prandial, respectively. Arginine, ornithine and citrulline levels were all significantly increased by the citrulline supplemented diets. In muscle, 8 amino acids were significantly altered by supplemented diets, while there were no significant changes in liver. Arginine was increased by 2% citrulline supplementation in muscle tissue. We also investigated the transcriptional responses of urea cycle, nitric oxide cycle and rate-limiting polyamine synthesis enzymes, related to arginine's metabolism, in liver. At both time points, only 2 enzymes were significantly altered by the supplemented diets, however several significant changes were observed comparing 3 h and 24 h post-prandial expression levels. Of these, the paralogous polyamine synthesis enzyme encoding genes ODC1 and ODC2 displayed the largest increases in 3 h post-prandial fish. These findings demonstrate that endogenous synthesis of arginine is possible from a citrulline supplemented diet and improve our understanding of arginine metabolism in fish.
    Keywords:  Arginine; Citrulline; Functional amino acids; Ornithine; Polyamine; Salmonids; Urea cycle
    DOI:  https://doi.org/10.1016/j.cbpa.2019.110632
  5. J Plant Physiol. 2019 Nov 26. pii: S0176-1617(19)30214-7. [Epub ahead of print]244 153085
    Benkő P, Jee S, Kaszler N, Fehér A, Gémes K.
      Several signaling pathways have been shown to be involved in the regulation of pollen germination and pollen tube elongation. Among others, exogenously applied polyamines were found to strongly affect pollen maturation, pollen tube emergence and elongation. In this study, our aim was to investigate the regulatory relation among exogenous polyamines, and endogenous reactive oxygen species and nitric oxide under pollen germination and the apical growth of pollen tube in tobacco plants. We have found that the various polyamines differentially affected the metabolism of nitric oxide and reactive oxygen species during the processes of pollen germination in the grain and the lengthening pollen tube. It is hypothesized that their differential effects might be related to their distinct influence on the endogenous nitric oxide and reactive oxygen species levels.
    Keywords:  Growth; Nitric oxide; Pollen germination; Polyamine; Reactive oxygen species; Tobacco
    DOI:  https://doi.org/10.1016/j.jplph.2019.153085
  6. RNA. 2019 Dec 11. pii: rna.072975.119. [Epub ahead of print]
    Sun W, Zhang X, Chen D, Murchie AIH.
      The 5' Untranslated region (5' UTR) of mRNAs play an important role in the eukaryotic translation initiation process. Additional levels of translational regulation may be mediated through interactions between structured mRNAs that can adopt interchangeable secondary or tertiary structures and the regulatory protein/RNA factors or components of the translational apparatus. Here we report a regulatory function of the 5' UTR mRNA of the spe2 gene (SAM decarboxylase) in polyamine metabolism of the fission yeast Schizosaccharomyces pombe. Reporter assays, biochemical experiments and mutational analysis demonstrate that this 5' UTR mRNA of spe2 can bind to spermidine to regulate translation. A tertiary structure transition in the 5' UTR RNA upon spermidine binding is essential for translation regulation. This study provides biochemical evidence for spermidine binding to regulate translation of the spe2 gene through interactions with the 5' UTR mRNA. The identification of such a regulatory RNA that is directly associated with an essential eukaryotic metabolic process suggests that other ligand-binding RNAs may also contribute to eukaryotic gene regulation.
    Keywords:  Regulatory RNA; Spermidine
    DOI:  https://doi.org/10.1261/rna.072975.119
  7. Psychopharmacology (Berl). 2019 Dec 11.
    Girardi BA, Fabbrin S, Wendel AL, Mello CF, Rubin MA.
      RATIONALE: Individuals with opioid use disorders often relapse into drug-seeking behavior after recalling memories linked to the drug use experience. Improving extinction efficacy has been used as a strategy to treat substance use disorders and suppress relapse. Although N-methyl-D-aspartate receptor (NMDAr) agonists facilitate acquisition, consolidation, and extinction, no study has addressed whether spermidine (SPD), a natural polyamine ligand of the NMDA receptor, facilitates the extinction and reinstatement of morphine-induced conditioned place preference (CPP).OBJECTIVES AND METHODS: The aim of the present study was to investigate the effect of SPD, an NMDAr agonist, on the extinction and reinstatement of morphine-induced CPP in mice. Adult male albino Swiss mice received saline (0.9% NaCl) or morphine (5 mg/kg) intraperitoneally (i.p.) and were respectively confined to a black or a white compartment for 30 min for four consecutive days for CPP induction. SPD (10-30 mg/kg, i.p.) or ifenprodil (NMDAr antagonist, 0.1-1 mg/kg, i.p.) were injected 15 min before extinction training.
    RESULTS: SPD and ifenprodil facilitated the extinction of morphine-induced CPP. SPD treatment during the extinction period impaired reinstatement induced by a priming dose of morphine (1.25 mg/kg). Ifenprodil (0.1 mg/kg) prevented the facilitatory effect of spermidine on the extinction of morphine-induced CPP but did not prevent reinstatement induced by morphine.
    CONCLUSIONS: These results suggest that SPD facilitated the extinction of morphine-induced CPP by modulating the polyamine binding site of the NMDA receptor. Our findings reveal important effects of SPD and ifenprodil on the re-exposure-induced decrease in morphine-induced CPP, which may be promising for developing novel pharmacological strategies to treat opioid use disorder.
    Keywords:  Conditioned place preference; Morphine; NMDA receptor; Opioid use disorders; Reinstatement; Spermidine
    DOI:  https://doi.org/10.1007/s00213-019-05403-z
  8. Talanta. 2020 Feb 01. pii: S0039-9140(19)31025-2. [Epub ahead of print]208 120392
    Navarro J, Sanz-Vicente I, Lozano R, de Marcos S, Galbán J.
      The joint determination of putrescine (Put) and cadaverine (Cad) in the presence of other biogenic amines is studied using their enzymatic reaction with diamine oxidase (DAO). Three alternative methods are studied based on the intrinsic colorimetric properties of DAO or horseradish peroxidase (HRP), and the use of 2,2'-Azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS) colorimetric reagent, respectively. In this last case an in-depth study is carried out in order to explain and solve some drawbacks usually associated with the use of this reagent (especially interferences, interaction with enzymes and instability), and to propose new analytical methodologies which this reagent allows to achieve (transient signal and the use of the violet species). Finally, the method has been applied to Put + Cad determination in a tuna sample without interference of other biogenic amines. The result has been compared with that obtained using a method based on HPLC-MS, which has allowed the new methodology to be validated.
    Keywords:  ABTS; Cadaverine; Diamine oxidase; HRP; Putrescine; Tuna
    DOI:  https://doi.org/10.1016/j.talanta.2019.120392
  9. Wien Klin Wochenschr. 2019 Dec 12.
    Pekar T, Wendzel A, Flak W, Kremer A, Pauschenwein-Frantsich S, Gschaider A, Wantke F, Jarisch R.
      Previous studies have highlighted that spermidine has the ability to trigger the important process of dissolving amyloid-beta plaques by autophagy. This manuscript focuses on the correlation of serum spermidine levels between age and between performance in mini-mental state examinations. It will serve as a premise for an ongoing multicentric placebo-controlled study, which focuses on the effect of oral spermidine supplementation on memory performance. Memory tests were carried out on 80 subjects aged 60-96 years old in 6 nursing homes in Styria. Blood samples were taken for the determination of spermidine concentration. The results showed a significant correlation between the spermidine concentration and the mini-mental state examination score (p = 0.025). On the basis of the dependence demonstrated it can be concluded that spermidine might be suitable as a biomarker for the diagnosis of neurocognitive changes (senile dementia or Alzheimer's disease).
    Keywords:  Alzheimer’s disease; CERAD Plus; Dementia; Memory performance; Spermidine
    DOI:  https://doi.org/10.1007/s00508-019-01588-7
  10. Br J Cancer. 2019 Dec 10.
    Urso L, Cavallari I, Sharova E, Ciccarese F, Pasello G, Ciminale V.
      Malignant pleural mesothelioma (MPM) is a rare malignancy of mesothelial cells with increasing incidence, and in many cases, dismal prognosis due to its aggressiveness and lack of effective therapies. Environmental and occupational exposure to asbestos is considered the main aetiological factor for MPM. Inhaled asbestos fibres accumulate in the lungs and induce the generation of reactive oxygen species (ROS) due to the presence of iron associated with the fibrous silicates and to the activation of macrophages and inflammation. Chronic inflammation and a ROS-enriched microenvironment can foster the malignant transformation of mesothelial cells. In addition, MPM cells have a highly glycolytic metabolic profile and are positive in 18F-FDG PET analysis. Loss-of-function mutations of BRCA-associated protein 1 (BAP1) are a major contributor to the metabolic rewiring of MPM cells. A subset of MPM tumours show loss of the methyladenosine phosphorylase (MTAP) locus, resulting in profound alterations in polyamine metabolism, ATP and methionine salvage pathways, as well as changes in epigenetic control of gene expression. This review provides an overview of the perturbations in metabolism and ROS homoeostasis of MPM cells and the role of these alterations in malignant transformation and tumour progression.
    DOI:  https://doi.org/10.1038/s41416-019-0661-9
  11. Circ Res. 2019 Dec 09.
    Tyrrell DJ, Blin M, Song J, Wood S, Zhang M, Beard DA, Goldstein D.
      Rationale: Aging is one of the strongest risk factors for atherosclerosis. Yet whether aging increases the risk of atherosclerosis independently of chronic hyperlipidemia is not known.Objective: To determine if vascular aging prior to the induction of hyperlipidemia enhances atherogenesis. Methods and Results: We analyzed the aortas of young and aged normolipidemic wild type (WT), disease free mice and found that aging led to elevated IL-6 levels and mitochondrial dysfunction, associated with increased mitophagy and the associated protein Parkin. In aortic tissue culture, we found evidence that with aging mitochondrial dysfunction and IL-6 exist in a positive feedback loop. We triggered acute hyperlipidemia in aged and young mice by inducing liver-specific degradation of the LDL receptor combined with a 10-week western diet and found that atherogenesis was enhanced in aged WT mice. Hyperlipidemia further reduced mitochondrial function and increased the levels of Parkin in the aortas of aged mice but not young mice. Genetic disruption of autophagy in smooth muscle cells of young mice exposed to hyperlipidemia led to increased aortic Parkin and IL-6 levels, impaired mitochondrial function, and enhanced atherogenesis. Importantly, enhancing mitophagy in aged, hyperlipidemic mice via oral administration of spermidine prevented the increase in aortic IL-6 and Parkin, attenuated mitochondrial dysfunction, and reduced atherogenesis. Conclusions: Prior to hyperlipidemia, aging elevates IL-6 and impairs mitochondrial function within the aorta, associated with enhanced mitophagy and increased Parkin levels. These age-associated changes prime the vasculature to exacerbate atherogenesis upon acute hyperlipidemia. Our work implies that novel therapeutics aimed at improving vascular mitochondrial bioenergetics or reducing inflammation before hyperlipidemia may reduce age-related atherosclerosis.
    Keywords:  atherosclerosis; hyperlipidemia
    DOI:  https://doi.org/10.1161/CIRCRESAHA.119.315644