bims-polyam Biomed News
on Polyamines
Issue of 2020‒08‒16
eight papers selected by
Alexander Ivanov
Engelhardt Institute of Molecular Biology

  1. mBio. 2020 Aug 11. pii: e01845-20. [Epub ahead of print]11(4):
      Amino acid metabolism is crucial for fungal growth and development. Ureohydrolases produce amines when acting on l-arginine, agmatine, and guanidinobutyrate (GB), and these enzymes generate ornithine (by arginase), putrescine (by agmatinase), or GABA (by 4-guanidinobutyrase or GBase). Candida albicans can metabolize and grow on arginine, agmatine, or guanidinobutyrate as the sole nitrogen source. Three related C. albicans genes whose sequences suggested that they were putative arginase or arginase-like genes were examined for their role in these metabolic pathways. Of these, Car1 encoded the only bona fide arginase, whereas we provide evidence that the other two open reading frames, orf19.5862 and orf19.3418, encode agmatinase and guanidinobutyrase (Gbase), respectively. Analysis of strains with single and multiple mutations suggested the presence of arginase-dependent and arginase-independent routes for polyamine production. CAR1 played a role in hyphal morphogenesis in response to arginine, and the virulence of a triple mutant was reduced in both Galleria mellonella and Mus musculus infection models. In the bloodstream, arginine is an essential amino acid that is required by phagocytes to synthesize nitric oxide (NO). However, none of the single or multiple mutants affected host NO production, suggesting that they did not influence the oxidative burst of phagocytes.IMPORTANCE We show that the C. albicans ureohydrolases arginase (Car1), agmatinase (Agt1), and guanidinobutyrase (Gbu1) can orchestrate an arginase-independent route for polyamine production and that this is important for C. albicans growth and survival in microenvironments of the mammalian host.
    Keywords:  Candida ; Candida albicans ; agmatinase; arginase; guanidinobutyrase; immunity; macrophages; morphogenesis
  2. J Nat Prod. 2020 Aug 12.
      The natural product allicin is a reactive sulfur species (RSS) from garlic (Allium sativum L.). Neuroblastoma (NB) is an early childhood cancer arising from the developing peripheral nervous system. Ornithine decarboxylase (ODC) is a rate-limiting enzyme in the biosynthesis of polyamines, which are oncometabolites that contribute to cell proliferation in NB and other c-MYC/MYCN-driven cancers. Both c-MYC and MYCN directly transactivate the E-box gene ODC1, a validated anticancer drug target. We identified allicin as a potent ODC inhibitor in a specific radioactive in vitro assay using purified human ODC. Allicin was ∼23 000-fold more potent (IC50 = 11 nM) than DFMO (IC50 = 252 μM), under identical in vitro assay conditions. ODC is a homodimer with 12 cysteines per monomer, and allicin reversibly S-thioallylates cysteines. In actively proliferating human NB cells allicin inhibited ODC enzyme activity, reduced cellular polyamine levels, inhibited cell proliferation (IC50 9-19 μM), and induced apoptosis. The natural product allicin is a new ODC inhibitor and could be developed for use in conjunction with other anticancer treatments, the latter perhaps at a lower than usual dosage, to achieve drug synergism with good prognosis and reduced adverse effects.
  3. Physiology (Bethesda). 2020 Sep 01. 35(5): 328-337
      Polyamines regulate a variety of physiological functions and are involved in pathogenesis of diverse human diseases. The epithelium of the mammalian gut mucosa is a rapidly self-renewing tissue in the body, and its homeostasis is preserved through well-controlled mechanisms. Here, we highlight the roles of cellular polyamines in maintaining the integrity of the gut epithelium, focusing on the emerging evidence of polyamines in the regulation of gut epithelial renewal and barrier function. Gut mucosal growth depends on the available supply of polyamines to the dividing cells in the crypts, and polyamines are also essential for normal gut epithelial barrier function. Polyamines modulate expression of various genes encoding growth-associated proteins and intercellular junctions via distinct mechanisms involving RNA-binding proteins and noncoding RNAs. With the rapid advance of polyamine biology, polyamine metabolism and transport are promising therapeutic targets in our efforts to protect the gut epithelium and barrier function in patients with critical illnesses.
    Keywords:  RNA-binding proteins; gut epithelial homeostasis; noncoding RNAs; polyamine biosynthesis; posttranscriptional regulation
  4. Metabolites. 2020 Aug 08. pii: E323. [Epub ahead of print]10(8):
      Metabolomic analysis is an emerging new diagnostic tool, which holds great potential for improving the understanding of osteoarthritis (OA)-caused metabolomic shifts associated with systemic inflammation and oxidative stress. The main aim of the study was to map the changes of amino acid, biogenic amine and complex lipid profiles in severe OA, where the shifts should be more eminent compared with early stages. The fasting serum of 70 knee and hip OA patients and 82 controls was assessed via a targeted approach using the AbsoluteIDQ™ p180 kit. Changes in the serum levels of amino acids, sphingomyelins, phoshatidylcholines and lysophosphatidylcholines of the OA patients compared with controls suggest systemic inflammation in severe OA patients. Furthermore, the decreased spermine to spermidine ratio indicates excessive oxidative stress to be associated with OA. Serum arginine level was positively correlated with radiographic severity of OA, potentially linking inflammation through NO synthesis to OA. Further, the level of glycine was negatively associated with the severity of OA, which might refer to glycine deficiency in severe OA. The current study demonstrates significant changes in the amino acid, biogenic amine and low-molecular weight lipid profiles of severe OA and provides new insights into the complex interplay between chronic inflammation, oxidative stress and OA.
    Keywords:  amino acids; arginine; glycine; lipidomics; lipids; lysophosphatidylcholine; metabolites; metabolomics; osteoarthritis; phosphatidylcholine
  5. Biol Pharm Bull. 2020 Aug 13.
      Depression is the most significant risk factor for suicide, yet the causes are complex and disease mechanism remains unclear. The incidence and disability rate of depression are very high and the efficacy of some traditional antidepressants is not completely satisfactory. Recently, some studies have found that benzofurans have anti-oxidation and anti-monoamine oxidase properties, which are related to depression. Euparin is a monomer compound of benzofuran, previous work by our team found that it improves the behavior of depressed mice. However, additional antidepressant effects and mechanisms of Euparin have not been reported. In this study, the Chronic Unpredictable Mild Stress (CUMS) model of mice was used to further investigate the effect and mechanism of Euparin on depression. Results showed that Euparin (8, 16 and 32 mg/kg) reduced depression-like behavior in mice compared with the model group. Meanwhile, all doses of Euparin were found to increase the contents of monoamine neurotransmitter and decrease monoamine oxidase and reactive oxygen species (ROS) levels in brain of depression mice. Additionally, Euparin restored CUMS-induced decrease of Spermidine / Spermine N1-Acetyltransferase 1 (SAT1), N-methyl-D-aspartate receptor subtype 2B (NMDAR2B) and Brain derived neurotrophic factor (BDNF) expression. These findings demonstrate that Euparin has antidepressant properties, and its mechanism involves the SAT1/NMDAR2B/BDNF signaling pathway.
    Keywords:  Brain derived neurotrophic factor; Depression; Euparin; Monoaminergic neurotransmitter; Oxidative stress; Signal pathway
  6. Environ Sci Pollut Res Int. 2020 Aug 07.
      Biogenic amines (BAs) are natural toxicants produced during the metabolism of their precursor amino acids or due to the proteolytic activities of some microorganisms. The objective of this study was to estimate the formed BAs in five types of the most commonly consumed and retailed cheese in Egypt. The examined cheese types included Feta, Karish, Mozzarella, Rumy, and Mish. Besides, the total mesophilic (TMC) and total psychrophilic (TPsC) bacterial counts were investigated. Furthermore, the estimated daily intakes (EDI) of BAs via the ingestion of various types of cheese were calculated, and their potential health risks were discussed. The achieved results indicated the formation of histamine (HIS), tyramine (TYR), cadaverine (CAD), putrescine, spermine, and spermidine at different concentrations. Except for Feta cheese, all samples (100%) of other cheese types had HIS concentrations higher than the established maximum permissible limits. Mish cheese contained the highest concentrations of total BAs, particularly, HIS, TYR, and CAD. TBA content showed significant positive correlations with TMC in the examined cheese types. The recorded EDI values of the different BAs in the current study would not have adverse effects. However, excessive consumption of cheese contaminated with BA might have serious health implications such as symptoms of histamine poisoning. Therefore, the adoption of strict hygienic measures during the production, storage, and distribution of cheese is highly recommended to reduce the formation of BAs in cheese.
    Keywords:  Biogenic amines; Cheese; Dietary intakes; Egypt; Microbial population; Risk assessment
  7. Chirality. 2020 Aug 13.
      In this work, we have characterized the interactions of monospermine porphyrin derivative with calf thymus DNA (ct-DNA) and poly (dG-dC)2 in both B and Z conformation. By several spectroscopic techniques (UV-vis, electronic circular dichroism and resonance light scattering), the binding modes of monospermine porphyrin derivative with different DNA sequences have been elucidated. In the presence of ct-DNA, the porphyrin binds along the external double helix as well as in the presence of B conformation of poly (dG-dC)2 . Whilst when the Z form of the poly (dG-dC)2 is induced, a slight intercalation of the porphyrin between the basis has been detected.
    Keywords:  DNA binding modes; Z-DNA; induced CD; porphyrin; spermine derivative