bims-polyam Biomed News
on Polyamines
Issue of 2019‒05‒19
eleven papers selected by
Alexander Ivanov
Engelhardt Institute of Molecular Biology


  1. J Integr Plant Biol. 2019 May 13.
    Lou YR, Ahmed S, Yan J, Adio AM, Powell HM, Morris PF, Jander G.
      Polyamines are small aliphatic amines found in almost all organisms, ranging from bacteria to plants and animals. In most plants, putrescine, the metabolic precursor for longer polyamines, such as spermidine and spermine, is produced from arginine, with either agmatine or ornithine as intermediates. Here we show that Arabidopsis thaliana (Arabidopsis) ADC1, one of the two known arginine decarboxylases in Arabidopsis, not only synthesizes agmatine from arginine, but also converts Nδ -acetylornithine to N-acetylputrescine. Phylogenetic analyses indicate that duplication and neofunctionalization of ADC1 and NATA1, the enzyme that synthesizes Nδ -acetylornithine in Arabidopsis, co-occur in a small number of related species in the Brassicaceae. Unlike ADC2, which is localized in the chloroplasts, ADC1 is in the endoplasmic reticulum together with NATA1, an indication that these two enzymes have access to the same substrate pool. Together, these results are consistent with a model whereby NATA1 and ADC1 together provide a pathway for the synthesis of N-acetylputrescine in Arabidopsis. This article is protected by copyright. All rights reserved.
    DOI:  https://doi.org/10.1111/jipb.12821
  2. Amino Acids. 2019 May 17.
    Yamori Y, Hamakawa M, Hidese R, Fukuda M, Atomi H, Fukuda W, Fujiwara S.
      Branched-chain polyamines (BCPAs) are unique polycations found in (hyper)thermophiles. Thermococcus kodakarensis grows optimally at 85 °C and produces the BCPA N4-bis(aminopropyl)spermidine by sequential addition of decarboxylated S-adenosylmethionine (dcSAM) aminopropyl groups to spermidine (SPD) by BCPA synthase A (BpsA). The T. kodakarensis bpsA deletion mutant (DBP1) did not grow at temperatures at or above 93 °C, and grew at 90 °C only after a long lag period following accumulation of excess cytoplasmic SPD. This suggests that BCPA plays an essential role in cell growth at higher temperatures and raises the possibility that BCPA is involved in controlling gene expression. To examine the effects of BCPA on transcription, the RNA polymerase (RNAP) core fraction was extracted from another bpsA deletion mutant, DBP4 (RNAPDBP4), which carried a His-tagged rpoL, and its enzymatic properties were compared with those of RNAP from wild-type (WT) cells (RNAPWT). LC-MS analysis revealed that nine ribosomal proteins were detected from RNAPWT but only one form RNAPDBP4. These results suggest that BCPA increases the linkage between RNAP and ribosomes to achieve efficient coupling of transcription and translation. Both RNAPs exhibited highest transcription activity in vitro at 80 °C, but the specific activity of RNAPDBP4 was lower than that of RNAPWT. Upon addition of SPD and BCPA, both increased the transcriptional activity of RNAPDBP4; however, elevation by BCPA was achieved at a tenfold lower concentration. Addition of BCPA also protected RNAPDBP4 against thermal inactivation at 90 °C. These results suggest that BCPA increases transcriptional activity in T. kodakarensis by stabilizing the RNAP complex at high temperatures.
    Keywords:  Archaea; Branched-chain polyamine; Hyperthermophile; Polyamine; RNA polymerase; Transcription
    DOI:  https://doi.org/10.1007/s00726-019-02745-y
  3. Int J Oncol. 2019 Jun;54(6): 2080-2094
    Ohkubo S, Mancinelli R, Miglietta S, Cona A, Angelini R, Canettieri G, Spandidos DA, Gaudio E, Agostinelli E.
      Amine oxidases, which contribute to the regulation of polyamine levels, catalyze the oxidative deamination of polyamines to generate H2O2 and aldehyde(s). In this study, and at least to the best of our knowledge, maize polyamine oxidase (ZmPAO) was used for the first time with the aim of identifying a novel strategy for cancer therapy. The cytotoxicity and the mechanisms of cell death induced by the enzymatic oxidation products of polyamine generated by ZmPAO were investigated. Exogenous spermine and ZmPAO treatment decreased cell viability in a spermine dose‑ and time‑dependent manner, particularly, the viability of the multidrug‑resistant (MDR) colon adenocarcinoma cells, LoVo DX, when compared with drug‑sensitive ones (LoVo WT). Further analyses revealed that H2O2 derived from spermine was mainly responsible for the cytotoxicity. Flow cytometric analysis revealed that treatment with ZmPAO and spermine increased the apoptotic population of LoVo WT and LoVo DX cells. In addition, we found that treatment with ZmPAO and spermine markedly reduced mitochondrial membrane potential in the LoVo DX cells, in agreement with the results of cell viability and apoptosis assays. Transmission electron microscopic observations supported the involvement of mitochondrial depolarization in the apoptotic process. Therefore, the dysregulation of polyamine metabolism in tumor cells may be a potential therapeutic target. In addition, the development of MDR tumor cells is recognized as a major obstacle in cancer therapy. Therefore, the design of a novel therapeutic strategy based on the use of this combination may be taken into account, making this approach attractive mainly in treating MDR cancer patients.
    DOI:  https://doi.org/10.3892/ijo.2019.4780
  4. Polymers (Basel). 2019 May 16. pii: E897. [Epub ahead of print]11(5):
    Cristiani C, Iannicelli-Zubiani EM, Dotelli G, Finocchio E, Gallo Stampino P, Licchelli M.
      Hybrid materials based on clays and polyamines are supposed to be efficient heavy metals sorbents due to the well-known adsorption behaviour of the clay matrix and to the coordination properties of un-protonated amino groups. For this purpose, a montmorillonite clay was modified with three different aliphatic polyamines: L6 and L10 have a linear structure with six and ten amino groups, respectively, while B14 is a branched polyamine with fourteen amino groups. Initial amine concentration was the main parameter investigated and data were fitted with Langmuir and Freundlich models. Interaction mechanisms between clay and amines were deeply investigated by different experimental techniques such as X-ray powder diffraction (XRD), thermal analysis measurements (DTG), Fourier Transform Infrared Spectroscopy (FT-IR) and diffuse reflectance (NIR) spectroscopy. Experimental results showed that the amount of amines efficiently immobilized in the solid phase can be increased by increasing the initial concentration of polyamines in the clay modification process. These data were best fitted by Freundlich model, indicating a presence of surface sites of different nature. In the resulting hybrid materials, neither the accessibility of the NH/NH2 groups of the amines, nor the accessibility of the structural OH of the clay was hindered. Several preliminary tests in La ions' uptake and release from aqueous solution were also carried out. In the conditions used for this study, total metal ion removal was achieved at sufficiently low linear amine loadings (i.e., 0.45 mmol/gclay for the small L6 amine), suggesting that these hybrid materials are promising for the proposed application in environmental remediation.
    Keywords:  clay-amine interaction mechanisms; la uptake and release; organo-clays; polyamines; structure effects
    DOI:  https://doi.org/10.3390/polym11050897
  5. Cancers (Basel). 2019 May 15. pii: E675. [Epub ahead of print]11(5):
    Choi BH, Coloff JL.
      Far beyond simply being 11 of the 20 amino acids needed for protein synthesis, non-essential amino acids play numerous important roles in tumor metabolism. These diverse functions include providing precursors for the biosynthesis of macromolecules, controlling redox status and antioxidant systems, and serving as substrates for post-translational and epigenetic modifications. This functional diversity has sparked great interest in targeting non-essential amino acid metabolism for cancer therapy and has motivated the development of several therapies that are either already used in the clinic or are currently in clinical trials. In this review, we will discuss the important roles that each of the 11 non-essential amino acids play in cancer, how their metabolic pathways are linked, and how researchers are working to overcome the unique challenges of targeting non-essential amino acid metabolism for cancer therapy.
    Keywords:  arginine; asparagine; aspartate; cancer; cysteine; glutamate; glutamine; glycine; proline; serine
    DOI:  https://doi.org/10.3390/cancers11050675
  6. Nature. 2019 May 14.
    Li L, Mao Y, Zhao L, Li L, Wu J, Zhao M, Du W, Yu L, Jiang P.
      In Fig. 1c of this Letter, the labels p53+/+ and p53-/- were inadvertently swapped. The original figure has been corrected online.
    DOI:  https://doi.org/10.1038/s41586-019-1121-7
  7. Int J Psychiatry Clin Pract. 2019 May 13. 1-6
    Yılmaz E, Şekeroğlu MR, Yılmaz E, Çokluk E.
      OBJECTIVES: Agmatine is a cationic amine resulting from the decarboxylation of l-arginine. Agmatine has neuroprotective, anti-inflammatory, anti-stress, and anti-depressant properties. In this study, plasma agmatine, arginine decarboxylase, and agmatinase levels were measured during manic episode and remission period in patients with bipolar disorder.METHODS: Thirty healthy volunteers and 30 patients who meet Bipolar Disorder Manic Episode diagnostic criteria were included in the study. Additionally, the changes in the patient group between manic episode and remission period were examined. We evaluated the relationship between levels of l-arginine and arginine decarboxylase in the agmatine synthesis pathway, and level of agmatinase that degrades agmatine.
    RESULTS: Levels of agmatine and l-arginine were significantly increased than control group during manic episode (p < .01). All parameters were increased during manic episode compared to remission period (p < .05). Agmatinase was significantly decreased both during manic episode (p < .01) and remission period (p < .05) in comparison to the control group. Arginine decarboxylase levels did not show a significant difference between the groups (p > .05).
    CONCLUSIONS: This study indicate that there may be a relationship between bipolar disorder and agmatine and its metabolic pathway. Nonetheless, we believe more comprehensive studies are needed in order to reveal the role of agmatine in etiology of bipolar disorder. Key points Agmantine, agmatinase, l-arginine and arginine decarboxylase levels in BD have not been explored before. Various neuro-chemical mechanisms act to increase agmatine in BD; however, agmatine could have elevated to compensate agmatine deficit prior to the manifestation of the disease as in schizophrenia. Elevated agmatine degradation resulting from excess expression of agmatinase which is suggested to be effective in pathogenesis of mood disorders was compensated by this way. Elevated agmatine may be one of the causes which play a role in mania development. Elevated agmatine levels are also suggested to trigger psychosis and be related with the etiology of manic episode and lead to BD.
    Keywords:  -arginine; Agmatine; agmatinase; arginine decarboxylase; bipolar disorder
    DOI:  https://doi.org/10.1080/13651501.2019.1569237
  8. Mol Cell Biochem. 2019 May 15.
    Mierzejewska P, Zabielska MA, Kutryb-Zajac B, Tomczyk M, Koszalka P, Smolenski RT, Slominska EM.
      Changes in the ecto-5'-nucleotidase activity-an extracellular nucleotide catabolic enzyme may lead to the inflammation and endothelial dysfunction. We investigated the effect of CD73 deletion on the endothelial function and L-arginine metabolism in various age groups of mice. 1-,3-,6-, and 12-month-old, male C57BL/6 J wild type (WT) and C57BL/6 J CD73-/- (CD73-/-) mice were used. Blood samples were used for the analysis of adenine nucleotide concentrations. Serum samples were analyzed for the concentration of amino acids, Interleukin 6 (IL-6), Intercellular Adhesion Molecule 1 (ICAM-1), Vascular Cell Adhesion Molecule 1 (VCAM-1), and endothelial nitric oxide synthase (eNOS) level. Serum and aortic nitrate/nitrite, as well as aortic arginase and NOS activity in endothelial cells (EC) were evaluated. CD73 deletion led to age-dependent increase in IL-6, ICAM-1, and VCAM-1 concentration compared to WT. All CD73-/- mice age groups were characterized by reduced L-Arginine concentration and eNOS level. Significantly lower NOS activity was noticed in EC isolated from CD73-/- mice lungs in comparison to EC isolated from WT lungs. The L-Arginine/ADMA ratio in the CD73-/- decreased in age-dependent manner in comparison to WT. The nitrate/nitrite ratio was reduced in serum and in aortas of 6-month-old CD73-/- mice as compared to WT. The ornithine/arginine and ornithine/citrulline ratios were increased in CD73-/- compared to controls. Blood (erythrocyte) Adenosine-5'-triphosphate and Adenosine-5'-diphosphate levels were reduced in favor to higher blood Adenosine-5'-monophosphate concentration in CD73-/- mice in comparison to WT. The CD73 deletion leads to the development of age-dependent endothelial dysfunction in mice, associated with impaired L-arginine metabolism. CD73 activity seems to protect endothelium.
    Keywords:  Adenosine; Ecto-5′-nucleotidase; Endothelial dysfunction; Endothelium; L-Arginine metabolism; Nucleotide metabolism
    DOI:  https://doi.org/10.1007/s11010-019-03537-4
  9. Biochem Biophys Res Commun. 2019 May 14. pii: S0006-291X(19)30912-X. [Epub ahead of print]
    Tsugawa Y, Handa H, Imai T.
      Arginine is a semi-essential amino acid with multiple functions, including stimulating the secretion of growth hormone (GH) and insulin-like growth factor 1 (IGF-1). IGF-1, which is produced by hepatocytes, plays important roles in cellular metabolism, proliferation, and growth. Previous studies showed that arginine-induced IGF-1 secretion occurs via two pathways: a GH-dependent pathway and an arginine-dependent pathway with an unknown mechanism. In this study, we identified the mechanisms regulating IGF-1 secretion. First, GH stimulates the translation of IGF-1 and increases IGF-1 protein levels, leading to IGF-1 secretion. As observed in fasted mice and hepatocytes cultivated in arginine-depleted medium, decreases in arginine concentrations resulted in IGF-1 retention in the endoplasmic reticulum. Arginine administration reverses this retention, leading to IGF-1 secretion. These data describe a novel IGF-1 secretion control system in the endoplasmic reticulum.
    Keywords:  Arginine; GH; IGF-1
    DOI:  https://doi.org/10.1016/j.bbrc.2019.05.044
  10. Clin Chim Acta. 2019 May 13. pii: S0009-8981(19)31862-5. [Epub ahead of print]
    Peng MZ, Cai YN, Shao YX, Zhao L, Jiang MY, Lin YT, Yin X, Sheng HY, Liu L.
      Urea cycle disorders (UCD) are inborn errors of ammonia detoxification in which early diagnosis and treatment are critical to prevent metabolic emergencies. Unfortunately, the diagnosis was often and pronounced delayed. To improve diagnosis, we developed herein a liquid chromatography-tandem mass spectrometry method to investigate the disturbance of amino acid profile caused by UCD. The method enabled absolute quantification of 48 amino acids (AAs) within 20 min. Only 2.5 μL plasma was required for the analysis. The lower limits of quantification for most AAs were 0.01 μmol/L. Method accuracies ranged from 89.9% to 113.4%. The within- and between-run coefficients of variation were 0.8-7.7% and 2.6-14.5%, respectively. With this method, age-specific reference values were established for 42 AAs by analyzing 150 samples from normal controls, and patients with different subtypes of UCD were successfully distinguished. The data of patients revealed that UCD not only disturbed the metabolism of urea cycle AAs and induced accumulation of ammonia detoxification AAs, but also interfered the metabolism of some nervous system related AAs, such as pipecolic acid and N-acetylaspartic acid. This data may provide new insight into pathogenesis for UCD.
    Keywords:  Amino acids; Homocitrulline; LC-MS/MS; Ornithine transcarbamylase deficiency; Urea cycle disorders
    DOI:  https://doi.org/10.1016/j.cca.2019.05.011
  11. Int J Syst Evol Microbiol. 2019 May 17.
    Kämpfer P, Busse HJ, McInroy JA, Criscuolo A, Clermont D, Glaeser SP.
      Two slightly beige-pigmented, Gram-stain-negative, rod-shaped bacterial strains, IMT-291T and IMT-297, were isolated from soil in a field located in Malvern, Alabama, USA. The source soil had been amended with humic acid and continuously used for the cultivation of worms used for fish bait. It is still conceivable that the source of the strains is from the humic acid amendment, although all attempts to isolate the novel phenotypes from the humic acid source have failed. The two strains were identical based on morphology, growth rate and subsequently by 16S rRNA gene sequences, but showed differences in genomic fingerprint patterns generated by rep-PCR. Phylogenetic analysis based on the 16S rRNA gene revealed a placement of the strain in a distinct cluster with Xinfangfangia soli (97.2 % 16S rRNA gene sequence similarity) and in close proximity to the genus Falsirhodobacter with highest 16S rRNA gene sequence similarity of 95.3 % to the type strain of Falsirhodobacter deserti . Sequence similarities to all other type strains were below 95.0 %. The chemotaxonomic analysis showed a clear similarity to the genus Xinfangfangia. The main cellular fatty acids of the strain were C18 : 1 ω7c, 11-methly-C18 : 1 ω7c and C16 : 0. The major quinone was ubiquinone Q-10. Phosphatidylethanolamine, phosphatidylmonomethylethanolamine, phosphatidylglycerol and phosphatidylcholine were predominant in the polar lipid profile. The polyamine pattern contained the major compound spermidine and moderate amounts of putrescine and cadaverine. The diamino acid of the peptidoglycan was meso-diaminopimelic acid. Based on phylogenetic, chemotaxonomic and phenotypic analyses we propose a new species of the genus Xinfangfangia , with the name Xinfangfangia humi sp. nov. and strain IMT-291T (=LMG 30636T=CIP 111625T=CCM 8858T) as type strain.
    DOI:  https://doi.org/10.1099/ijsem.0.003434