bims-polyam Biomed News
on Polyamines
Issue of 2019‒09‒22
ten papers selected by
Alexander Ivanov
Engelhardt Institute of Molecular Biology


  1. Molecules. 2019 Sep 14. pii: E3351. [Epub ahead of print]24(18):
    Li J, Zhang L, Xiong J, Cheng X, Huang Y, Su Z, Yi M, Liu S.
      Polyamines are positively charged small molecules ubiquitously existing in all living organisms, and they are considered as one kind of the most ancient cellular components. The most common polyamines are spermidine, spermine, and their precursor putrescine generated from ornithine. Polyamines play critical roles in cells by stabilizing chromatin structure, regulating DNA replication, modulating gene expression, etc., and they also affect the structure and function of proteins. A few studies have investigated the impact of polyamines on protein structure and function previously, but no reports have focused on a protein-based biological module with a dedicated function. In this report, we investigated the impact of polyamines (putrescine, spermidine, and spermine) on the cyanobacterial KaiABC circadian oscillator. Using an established in vitro reconstitution system, we noticed that polyamines could disrupt the robustness of the KaiABC oscillator by inducing the denaturation of the Kai proteins (KaiA, KaiB, and KaiC). Further experiments showed that the denaturation was likely due to the induced change of the thermal stability of the clock proteins. Our study revealed an intriguing role of polyamines as a component in complex cellular environments and would be of great importance for elucidating the biological function of polyamines in future.
    Keywords:  biological module; circadian clock; kai proteins; polyamine; protein stability
    DOI:  https://doi.org/10.3390/molecules24183351
  2. Amino Acids. 2019 Sep 20.
    Hanff E, Bollenbach A, Beckmann B, Brunner G, Tsikas D.
      Gas chromatography-mass spectrometry (GC-MS) methods were developed, validated and used to measure serum spermidine (SPD) and putrescine (PUT) in 9 seropositive Helicobacter pylori (Hp +) and 18 seronegative Helicobacter pylori (Hp -) subjects (31-105 years). Homoarginine (hArg) was also measured by GC-MS. There were no statistical differences (unpaired t test) between the Hp + and Hp - subjects with respect to the serum concentrations of SPD (67.6 ± 40.3 vs. 93.7 ± 37.7 nM, P = 0.109), PUT (220 ± 139 vs. 236 ± 85 nM, P = 0.708) and hArg (1.60 ± 0.64 µM vs. 1.83 ± 0.74 µM, P = 0.554). Serum SPD and hArg concentrations correlated with each other (r = 0.426, P = 0.026, n = 27). The PUT/SPD molar ratio correlated inversely with the hArg concentration (r = - 0.406, P = 0.034, n = 27) and proteinic citrulline (r = - 0.487, P = 0.01, n = 27). These results suggest that SPD and PUT synthesis is associated with hArg formation and protein citrullination in healthy elderly subjects. The mechanisms underlying these associations and their significance remain to be elucidated.
    Keywords:  AGAT; Amino acids; Biogenic amines; GC–MS; Polyamines; Serum
    DOI:  https://doi.org/10.1007/s00726-019-02786-3
  3. Plant Signal Behav. 2019 Sep 17. 1667730
    Tailor A, Tandon R, Bhatla SC.
      Free polyamine (PA) titers in plants may be regulated through reversible conjugate formation and/or through modulation of their synthesis, transport and degradation. PA signaling involves the well-acknowledged signaling molecule, nitric oxide (NO), which functions in diverse biological processes. Present investigations demonstrate the influence of salt stress (120 mM NaCl) and exogenous NO donor (250 µM Diethylenetriamine, DETA) on PA homeostasis of 2 d old, etiolated sunflower (Helianthus annuus L.) seedling cotyledons as a long-distance signaling response. Significantly enhanced intracellular spermine (Spm) accumulation was observed in seedling cotyledons under salt stress and in response to NO donor, the increase being more pronounced in seedlings treated with NO, evidently as a result of upregulation of the PA biosynthetic enzymes - arginine decarboxylase (ADC) and S-adenosylmethionine decarboxylase (SAMDC) - as revealed by Western blot and confocal imaging (CLSM). Moreover, salt stress induced the activity of polyamine oxidase (PAO), a PA catabolic enzyme, while NO lowered its activity in salt-stressed seedling cotyledons. NO, thus, appears to assist the seedlings in adapting to salt stress by positively regulating PA homeostasis through regulation of PA distribution between free, conjugated and bound forms, increased accumulation of PA biosynthetic enzymes and lowering the rate of PA catabolism.
    Keywords:  ADC; DAO; ODC; PAO; SAMDC; nitric oxide; polyamine; salt stress; spermine
    DOI:  https://doi.org/10.1080/15592324.2019.1667730
  4. Urologiia. 2019 Sep; 74-79
    Ploskonos MV, Evdokimov VV.
      The aim of the study was to compare the content of polyamines (spermine and spermidine) in the seminal plasma of men of different fertility and to reveal the relationship between their level in sperm and the presence of markers of apoptosis in gametes.MATERIALS AND METHODS: ejaculates of 34 fertile men and 40 infertile men with various forms of subfertility between the ages of 22 and 40 were examined. The determination of polyamines was carried out by electrophoretic fractionation in an agar gel. As markers of apoptosis, externalization of phosphatidylserine (PS) to the external side of the spermatozoon membrane was determined and the receptor for the initiation of apoptosis CD95 in the gametes was detected.
    RESULTS: In sperm of infertile men, more spermatozoa with markers of apoptosis were revealed in comparison with fertile donors (p0,001). Against the background of a general decrease in the concentration of polyamines in ejaculates of infertile patients, the ratio between polyamines with a predominance of sperm in the seminal fluid is observed, which is the initiating factor for the initiation of apoptosis in gametes. This was proved by the relationship between the externalization of FS in gametes and the concentration of sperm in the spermoplasm in accordance with the coefficient of positive correlation (r=0.5, p<0.01).
    CONCLUSIONS: Thus, a change in the concentration of polyamines in the seminal fluid of men is one of the factors in the regulation of apoptosis of the sex cells. Determination of the content of polyamines in seminal plasma can be recommended to increase the information content of the study of the causes of impaired fertility of the ejaculate, and the results obtained for the development of the algorithm for examining infertile patients.
    Keywords:  fertility; markers of apoptosis; polyamines; spermatozoa; spermoplasm
  5. Alcohol. 2019 Sep 11. pii: S0741-8329(19)30050-3. [Epub ahead of print]
    Chimthanawala N, Patil S, Agrawal R, Kotagale NR, Umekar MJ, Taksande BG.
      Although ethanol withdrawal depression is one of the prominent reasons for its reinstatement and dependence, its neurochemical basis is not clearly understood. Present study investigated the role of agmatinergic system in ethanol withdrawal-induced depression using forced swim test (FST) in rats. Chronic exposure of animals to ethanol for 21 days and its abrupt withdrawal produced depression like behavior as evidenced by increased immobility time in FST, compared to the pair-fed control animals. The ethanol withdrawal-induced depression was significantly attenuated by agmatine (20-40 μg/rat, i.c.v.), moxonidine (50 μg/rat, i.c.v.), 2-BFI (20 μg/rat, i.c.v.), L-arginine (80 μg/rat, i.c.v.), amino-guanidine (25 μg/rat, i.c.v.) and arcaine (50 μg/rat, i.c.v.) by their once daily administration during the withdrawal phase (Day 21, 22 and 23). The antidepressant effect of agmatine in ethanol withdrawn rats was potentiated by imidazoline receptor I1 agonist, moxonidine (25 μg/rat, i.c.v.) and imidazoline receptor I2 agonist 2-BFI (10 μg/rat, i.c.v.) at their sub-effective doses. On the other hand, it was completely blocked by imidazoline receptor I1 antagonist, efaroxan (10 μg/rat, i.c.v.) and imidazoline receptor I2 antagonist, idazoxan (4 μg/rat, i.c.v.). In addition, agmatine levels were significantly reduced in brain samples of ethanol withdrawn rats as compared to the pair-fed control animals. In conclusion, the present study suggests the importance of endogenous agmatinergic system and imidazoline receptors system in ethanol withdrawal-induced depression. The data projects agmatine as a potential therapeutic target for the alcohol withdrawal-induced depression.
    Keywords:  Agmatine; ethanol; forced swim test; imidazoline receptors; withdrawal depression
    DOI:  https://doi.org/10.1016/j.alcohol.2019.09.002
  6. Viruses. 2019 Sep 16. pii: E861. [Epub ahead of print]11(9):
    Wang LL, Swevers L, Rombouts C, Meeus I, Van Meulebroek L, Vanhaecke L, Smagghe G.
      How a host metabolism responds to infection with insect viruses and how it relates to pathogenesis, is little investigated. Our previous study observed that Cricket paralysis virus (CrPV, Dicistroviridae) causes short term persistence in silkworm Bm5 cells before proceeding to acute infection. In this study, a metabolomics approach based on high resolution mass spectrometry was applied to investigate how a host metabolism is altered during the course of CrPV infection in Bm5 cells and which changes are characteristic for the transition from persistence to pathogenicity. We observed that CrPV infection led to significant and stage-specific metabolic changes in Bm5 cells. Differential metabolites abundance and pathway analysis further identified specific metabolic features at different stages in the viral life cycle. Notably, both glucose and glutamine levels significantly increased during CrPV persistent infection followed by a steep decrease during the pathogenic stages, suggesting that the central carbon metabolism was significantly modified during CrPV infection in Bm5 cells. In addition, dynamic changes in levels of polyamines were detected. Taken together, this study characterized for the first time the metabolic dynamics of CrPV infection in insect cells, proposing a central role for the regulation of both amino acid and carbohydrate metabolism during the period of persistent infection of CrPV in Bm5 cells.
    Keywords:  Cricket paralysis virus; host metabolism; metabolomics; persistent infection; silkworm
    DOI:  https://doi.org/10.3390/v11090861
  7. Free Radic Biol Med. 2019 Sep 11. pii: S0891-5849(19)31344-9. [Epub ahead of print]143 534-544
    Chen J, Li H, Yang K, Wang Y, Yang L, Hu L, Liu R, Shi Z.
      Melatonin, a phytochemical, can regulate lateral root (LR) formation, but the downstream signaling of melatonin remains elusive. Here we investigated the roles of hydrogen peroxide (H2O2) and superoxide radical (O2•‾) in melatonin-promoted LR formation in tomato (Solanum lycopersicum) roots by using physiological, histochemical, bioinformatic, and biochemical approaches. The increase in endogenous melatonin level stimulated reactive oxygen species (ROS)-dependent development of lateral root primordia (LRP) and LR. Melatonin promoted LRP/LR formation and modulated the expression of cell cycle genes (SlCDKA1, SlCYCD3;1, and SlKRP2) by stimulating polyamine oxidase (PAO)-dependent H2O2 production and respiratory burst oxidase homologue (Rboh)-dependent O2•‾ production, respectively. Screening of SlPAOs and SlRbohs gene family combined with gene expression analysis suggested that melatonin-promoted LR formation was correlated to the upregulation of SlPAO1, SlRboh3, and SlRboh4 in LR-emerging zone. Transient expression analysis confirmed that SlPAO1 was able to produce H2O2 while SlRboh3 and SlRboh4 were capable of producing O2•‾. Melatonin-ROS signaling cassette was also found in the regulation of LR formation in rice root and lateral hyphal branching in fungi. These results suggested that SlPAO1-H2O2 and SlRboh3/4-O2•‾ acted as downstream of melatonin to regulate the expression of cell cycle genes, resulting in LRP initiation and LR development. Such findings uncover one of the regulatory pathways for melatonin-regulated LR formation, which extends our knowledge for melatonin-regulated plant intrinsic physiology.
    Keywords:  Hydrogen peroxide; Lateral root; Melatonin; Polyamine oxidase; RBOH; Reactive oxygen species; Superoxide radical
    DOI:  https://doi.org/10.1016/j.freeradbiomed.2019.09.011
  8. WMJ. 2019 Jul;118(2): 98-100
    Wang B, Jha P.
      INTRODUCTION: Urea cycle disorders are metabolic disorders of nitrogenous waste substances due to either complete or partial deficiency of enzymes. Hyperammonemia associated with urea cycle disorders should be addressed immediately in the acute setting, as it can cause irreversible neurological injury or death.CASE PRESENTATION: We report the case of a 48-year-old woman who presented with lethargy, weakness, and altered mental status following prolonged nausea and vomiting despite an esophageal dilatation procedure 3 weeks prior. Further investigation with assistance from the genetics consult team revealed a partial enzyme deficiency associated with urea cycle disorder.
    DISCUSSION: Although many cases of urea cycle disorder present in neonates 24 to 48 hours following birth, a delayed presentation may be observed in female carriers with partial activity of any urea cycle enzyme leading to ammonia buildup. This is the result of stress-related events that form a catabolic state involving protein breakdown within the body that trigger increased ammonia levels.
    CONCLUSION: A diagnosis of urea cycle disorder should be suspected in patients who have had a recent stressor with progressive lethargy and confusion associated with hyperammonemia, so that treatment may begin with intravenous sodium benzoate and phenylacetate initially and hemodialysis at 8 hours if ammonia levels do not decrease to avoid permanent neurologic damage.
  9. Stem Cell Reports. 2019 Sep 04. pii: S2213-6711(19)30301-7. [Epub ahead of print]
    Akbari S, Sevinç GG, Ersoy N, Basak O, Kaplan K, Sevinç K, Ozel E, Sengun B, Enustun E, Ozcimen B, Bagriyanik A, Arslan N, Önder TT, Erdal E.
      Organoid technologies have become a powerful emerging tool to model liver diseases, for drug screening, and for personalized treatments. These applications are, however, limited in their capacity to generate functional hepatocytes in a reproducible and efficient manner. Here, we generated and characterized the hepatic organoid (eHEPO) culture system using human induced pluripotent stem cell (iPSC)-derived EpCAM-positive endodermal cells as an intermediate. eHEPOs can be produced within 2 weeks and expanded long term (>16 months) without any loss of differentiation capacity to mature hepatocytes. Starting from patient-specific iPSCs, we modeled citrullinemia type 1, a urea cycle disorder caused by mutations in the argininosuccinate synthetase (ASS1) enzyme. The disease-related ammonia accumulation phenotype in eHEPOs could be reversed by the overexpression of the wild-type ASS1 gene, which also indicated that this model is amenable to genetic manipulation. Thus, eHEPOs are excellent unlimited cell sources to generate functional hepatic organoids in a fast and efficient manner.
    Keywords:  3D organoid; EpCAM; citrullinemia; disease modelling; hepatocyte; hepatocyte differentiation; iPSC; liver
    DOI:  https://doi.org/10.1016/j.stemcr.2019.08.007
  10. Langmuir. 2019 Sep 20.
    Safinya CR, Chung PJ, Song C, Li Y, Miller HP, Choi MC, Raviv U, Ewert KK, Wilson L, Feinstein SC.
      In this mini-review, which is part of a special issue in honor of Jacob N. Israelachvili's remarkable research career on intermolecular forces and interfacial science, we present studies of structures, phase behavior, and forces in reaction mixtures of microtubules (MTs) and tubulin oligomers, with either intrinsically disordered protein (IDP) Tau, cationic vesicles, or the polyamine spermine (4+). Bare MTs consist of thirteen protofilaments (PFs) on average where each PF is made of a linear stack of αβ-tubulin dimers (i.e. tubulin oligomers). We begin with a series of experiments, which demonstrate the flexibility of PFs towards shape changes in response to local environmental cues. First, studies show that MT-associated protein (MAP) Tau controls the diameter of microtubules upon binding to the outer surface implying a shape change in the cross-sectional area of PFs forming the MT perimeter. The diameter of a MT may also be controlled by the charge density of a lipid bilayer membrane that coats the outer surface. We further describe an experimental study where it is unexpectedly found that the biologically relevant polyamine spermine (+4e) is able to depolymerize taxol-stabilized microtubules with efficiency that increases with decreasing temperature. This MT destabilization drives a dynamical structural transition where inside-out curving of PFs, during the depolymerization peeling process, is followed by re-assembly of ring-like curved PF building blocks into an array of helical inverted tubulin tubules. We finally turn to a very recent study on pressure-distance measurements in bundles of MTs employing the small-angle X-ray scattering (SAXS)-osmotic pressure technique, which complements the Surface-Forces Apparatus technique developed by Jacob N. Israelachvili. These latter studies are among the very few, which are beginning to shed light on the precise nature of the interactions between MTs mediated by MAP Tau in 37°C reaction mixtures containing GTP and lacking taxol.
    DOI:  https://doi.org/10.1021/acs.langmuir.9b02208