bims-polyam Biomed News
on Polyamines
Issue of 2022–03–20
seven papers selected by
Sebastian J. Hofer, University of Graz
  1. Environmental stress tolerance in maize (Zea mays): role of polyamine metabolism.
  2. The effect of spermidine on autoimmunity and beta cell function in NOD mice.
  3. Expression of polyamines and its association with GnRH-I in the hypothalamus during aging in rodent model.
  4. Quantitative input-output dynamics of a c-di-GMP signal transduction cascade in Vibrio cholerae.
  5. Caging Polycations: Effect of Increasing Confinement on the Modes of Interaction of Spermidine3+ With DNA Double Helices.
  6. Angiocrine polyamine production regulates adiposity.
  7. Deaccelerated Myogenesis and Autophagy in Genetically Induced Pulmonary Emphysema.
  1. Funct Plant Biol. 2022 Mar 18.
    Environmental stress tolerance in maize (Zea mays): role of polyamine metabolism.
    Salika Ramazan, Ifra Nazir, Waseem Yousuf, Riffat John.
      Maize (Zea mays L.), a major multipurpose crop for food, feed and energy is extremely susceptible to environmental perturbations and setting off the major factors for limiting maize yield. Generally, plant yields are reduced and significantly lost to adverse environments and biotic strains. To ensure the safety of living cells under unfavourable circumstances, polyamines (PAs) play an important role in regulating the response under both abiotic and biotic stresses. It is the relative abundance of higher PAs (spermidine, Spd; spermine, Spm) vis-à-vis the diamine putrescine (Put) and PA catabolism that determines the stress tolerance in plants. Climate changes and increasing demands for production of maize have made it pressing to improve the stress tolerance strategies in this plant and it is imperative to understand the role of PAs in response to various environmental perturbations. Here, we critically review and summarise the recent literature on role of PAs in conferring stress tolerance in the golden crop. The responses in terms of PA accumulation, their mechanism of action and all the recent genetic manipulation studies carried out in PA metabolism pathway, ameliorating range of abiotic and biotic stresses have been discussed. As PA metabolism under stress conditions does not operate singly within cells and is always linked to other metabolic pathways in maize, its complex connections and role as a signalling molecule have also been discussed in this review.
    DOI:  https://doi.org/10.1071/FP21324
  2. Sci Rep. 2022 Mar 16. 12(1): 4502
    The effect of spermidine on autoimmunity and beta cell function in NOD mice.
    Ceren Karacay, Barbara Prietl, Clemens Harer, Barbara Ehall, Christoph W Haudum, Kaddour Bounab, Joakim Franz, Tobias Eisenberg, Frank Madeo, Dagmar Kolb, Kerstin Hingerl, Markus Hausl, Christoph Magnes, Selma I Mautner, Petra Kotzbeck, Thomas R Pieber.
      Spermidine is a natural polyamine which was shown to prolong lifespan of organisms and to improve cardiac and cognitive function. Spermidine was also reported to reduce inflammation and modulate T-cells. Autophagy is one of the mechanisms that spermidine exerts its effect. Autophagy is vital for β-cell homeostasis and autophagy deficiency was reported to lead to exacerbated diabetes in mice. The effect of spermidine in type 1 diabetes pathogenesis remains to be elucidated. Therefore, we examined the effect of spermidine treatment in non-obese diabetic (NOD) mice, a mouse model for type 1 diabetes. NOD mice were given untreated or spermidine-treated water ad libitum from 4 weeks of age until diabetes onset or 35 weeks of age. We found that treatment with 10 mM spermidine led to higher diabetes incidence in NOD mice despite unchanged pancreatic insulitis. Spermidine modulated tissue polyamine levels and elevated signs of autophagy in pancreas. Spermidine led to increased proportion of pro-inflammatory T-cells in pancreatic lymph nodes (pLN) in diabetic mice. Spermidine elevated the proportion of regulatory T-cells in early onset mice, whereas it reduced the proportion of regulatory T-cells in late onset mice. In summary spermidine treatment led to higher diabetes incidence and elevated proportion of T-cells in pLN.
    DOI:  https://doi.org/10.1038/s41598-022-08168-2
  3. Amino Acids. 2022 Mar 14.
    Expression of polyamines and its association with GnRH-I in the hypothalamus during aging in rodent model.
    Nayan Mate, Rohit Shaji, Moitreyi Das, Sammit Jain, Arnab Banerjee.
      GnRH-I and GnIH are the key neuropeptides that regulate the hypothalamic-pituitary-gonadal axis in mammals during aging. Polyamines are important aliphatic amines that are expressed in the brain and show variation with aging. The present study demonstrates evidence of variation in the level of expression of polyamines, GnRH-I and GnIH in the hypothalamus of female mice during aging. The study also suggests regulatory effects of polyamines over expression of the hypothalamic GnRH-I. The study shows a significant positive correlation between polyamines, its associated factors and GnRH-I along with significant negative correlation between polyamines, its associated factors and GnIH. This is the first study to report the effect of polyamines along with lactate or TNF-α or both on GnRH-I expression in GT1-7 cell line. TNF-α and lactate significantly decreased hypothalamic GnRH-I mRNA expression in GT1-7 cells when treated for 24 h. Polyamines (putrescine and agmatine) in contrast, significantly increased GnRH-I mRNA expression in GT1-7 cells when treated for 24 h. Also, polyamines increased GnRH-I mRNA expression when treated in presence of TNF-α or lactate thereby suggesting its neuro-protective role. This study also found 3809 differentially expressed genes through RNA-seq done between the hypothalamic GT1-7 cells treated with putrescine only versus TNF-α and putrescine. The present study suggests for the first time that putrescine treatment to TNFα-primed GT1-7 cells upregulates GnRH-I expression via regulation of several pathways such as calcium ion pathway, estrogen signaling, clock genes as well as regulating other metabolic process like neuronal differentiation and neurulation.
    Keywords:  Aging; GnIH; GnRH-I; Hypothalamus; Polyamine
    DOI:  https://doi.org/10.1007/s00726-022-03139-3
  4. PLoS Biol. 2022 Mar 18. 20(3): e3001585
    Quantitative input-output dynamics of a c-di-GMP signal transduction cascade in Vibrio cholerae.
    Andrew A Bridges, Jojo A Prentice, Chenyi Fei, Ned S Wingreen, Bonnie L Bassler.
      Bacterial biofilms are multicellular communities that collectively overcome environmental threats and clinical treatments. To regulate the biofilm lifecycle, bacteria commonly transduce sensory information via the second messenger molecule cyclic diguanylate (c-di-GMP). Using experimental and modeling approaches, we quantitatively capture c-di-GMP signal transmission via the bifunctional polyamine receptor NspS-MbaA, from ligand binding to output, in the pathogen Vibrio cholerae. Upon binding of norspermidine or spermidine, NspS-MbaA synthesizes or degrades c-di-GMP, respectively, which, in turn, drives alterations specifically to biofilm gene expression. A long-standing question is how output specificity is achieved via c-di-GMP, a diffusible molecule that regulates dozens of effectors. We show that NspS-MbaA signals locally to specific effectors, sensitizing V. cholerae to polyamines. However, local signaling is not required for specificity, as changes to global cytoplasmic c-di-GMP levels can selectively regulate biofilm genes. This work establishes the input-output dynamics underlying c-di-GMP signaling, which could be useful for developing bacterial manipulation strategies.
    DOI:  https://doi.org/10.1371/journal.pbio.3001585
  5. Front Chem. 2022 ;10 836994
    Caging Polycations: Effect of Increasing Confinement on the Modes of Interaction of Spermidine3+ With DNA Double Helices.
    Tudor Vasiliu, Francesca Mocci, Aatto Laaksonen, Leon De Villiers Engelbrecht, Sergiy Perepelytsya.
      Polyamines have important roles in the modulation of the cellular function and are ubiquitous in cells. The polyamines putrescine2+, spermidine3+, and spermine4+ represent the most abundant organic counterions of the negatively charged DNA in the cellular nucleus. These polyamines are known to stabilize the DNA structure and, depending on their concentration and additional salt composition, to induce DNA aggregation, which is often referred to as condensation. However, the modes of interactions of these elongated polycations with DNA and how they promote condensation are still not clear. In the present work, atomistic molecular dynamics (MD) computer simulations of two DNA fragments surrounded by spermidine3+ (Spd3+) cations were performed to study the structuring of Spd3+ "caged" between DNA molecules. Microsecond time scale simulations, in which the parallel DNA fragments were constrained at three different separations, but allowed to rotate axially and move naturally, provided information on the conformations and relative orientations of surrounding Spm3+ cations as a function of DNA-DNA separation. Novel geometric criteria allowed for the classification of DNA-Spd3+ interaction modes, with special attention given to Spd3+ conformational changes in the space between the two DNA molecules (caged Spd3+). This work shows how changes in the accessible space, or confinement, around DNA affect DNA-Spd3+ interactions, information fundamental to understanding the interactions between DNA and its counterions in environments where DNA is compacted, e.g. in the cellular nucleus.
    Keywords:  DNA; condensation; counterion; molecular dynamics; polyamine
    DOI:  https://doi.org/10.3389/fchem.2022.836994
  6. Nat Metab. 2022 Mar 14.
    Angiocrine polyamine production regulates adiposity.
    Erika Monelli, Pilar Villacampa, Amaia Zabala-Letona, Anabel Martinez-Romero, Judith Llena, Daniel Beiroa, Leonor Gouveia, Iñigo Chivite, Sebastián Zagmutt, Pau Gama-Perez, Oscar Osorio-Conles, Laia Muixi, Ainara Martinez-Gonzalez, Sandra D Castillo, Natalia Martín-Martín, Pau Castel, Lorea Valcarcel-Jimenez, Irene Garcia-Gonzalez, Josep A Villena, Sonia Fernandez-Ruiz, Dolors Serra, Laura Herrero, Rui Benedito, Pablo Garcia-Roves, Josep Vidal, Paul Cohen, Rubén Nogueiras, Marc Claret, Arkaitz Carracedo, Mariona Graupera.
      Reciprocal interactions between endothelial cells (ECs) and adipocytes are fundamental to maintain white adipose tissue (WAT) homeostasis, as illustrated by the activation of angiogenesis upon WAT expansion, a process that is impaired in obesity. However, the molecular mechanisms underlying the crosstalk between ECs and adipocytes remain poorly understood. Here, we show that local production of polyamines in ECs stimulates adipocyte lipolysis and regulates WAT homeostasis in mice. We promote enhanced cell-autonomous angiogenesis by deleting Pten in the murine endothelium. Endothelial Pten loss leads to a WAT-selective phenotype, characterized by reduced body weight and adiposity in pathophysiological conditions. This phenotype stems from enhanced fatty acid β-oxidation in ECs concomitant with a paracrine lipolytic action on adipocytes, accounting for reduced adiposity. Combined analysis of murine models, isolated ECs and human specimens reveals that WAT lipolysis is mediated by mTORC1-dependent production of polyamines by ECs. Our results indicate that angiocrine metabolic signals are important for WAT homeostasis and organismal metabolism.
    DOI:  https://doi.org/10.1038/s42255-022-00544-6
  7. Am J Respir Cell Mol Biol. 2022 Mar 14.
    Deaccelerated Myogenesis and Autophagy in Genetically Induced Pulmonary Emphysema.
    Joseph Balnis, Lisa A Drake, Diane V Singer, Catherine E Vincent, Tanner C Korponay, Jeanine D'Armiento, Chun Geun Lee, Jack A Elias, Harold A Singer, Ariel Jaitovich.
      Patients with chronic obstructive pulmonary disease (COPD)-pulmonary emphysema often develop locomotor muscle dysfunction, which entails reduced muscle mass and force-generation capacity and is associated with worse outcomes including higher mortality. Myogenesis contributes to adult muscle integrity during injury-repair cycles. Injurious events crucially occur in COPD patients' skeletal muscles in the setting of exacerbations and infections which lead to acute decompensations for limited periods of time after which patients typically fail to recover the baseline status they had before the acute event. Autophagy, which is dysregulated in muscles from COPD patients, is a key regulator of satellite cells activation and myogenesis, yet very little research has so far investigated the mechanistic role of autophagy dysregulation in COPD muscles. Using a genetically inducible interleukin-13-driven pulmonary emphysema model leading to muscle dysfunction, and confirmed with a second genetic animal model, we found a significant myogenic dysfunction associated with satellite cells reduced proliferative capacity. Transplantation experiments followed by lineage tracing suggest that an intrinsic defect in satellite cells, and not in the COPD environment, plays a dominant role in the observed myogenic dysfunction. RNA sequencing analysis and direct observation of COPD mice satellite cells suggest dysregulated autophagy. Moreover, while autophagy flux experiments with bafilomycin demonstrated COPD mice satellite cells deacceleration of autophagosome turnover, spermidine-induced autophagy stimulation leads to higher replication rate and myogenesis in these animals. Our data suggests that pulmonary emphysema causes a disrupted myogenesis, which could be improved with stimulation of autophagy and satellite cells activation, leading to an attenuated muscle.
    Keywords:  COPD; autophagy; myogenesis; pulmonary emphysema; satellite cells
    DOI:  https://doi.org/10.1165/rcmb.2021-0351OC
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