bims-polyam Biomed News
on Polyamines
Issue of 2021–02–14
eleven papers selected by
Sebastian J. Hofer, University of Graz
  1. Health-Promoting Effects of Dietary Polyamines.
  2. Ornithine decarboxylase genes contribute to S-RNase-independent pollen rejection.
  3. Dual targeting of polyamine synthesis and uptake in diffuse intrinsic pontine gliomas.
  4. Role of CgTpo4 in Polyamine and Antimicrobial Peptide Resistance: Determining Virulence in Candida glabrata.
  5. A new insight into the contribution of putrescine to defense in Arabidopsis thaliana.
  6. Modulation of Ion Transport Across Plant Membranes by Polyamines: Understanding Specific Modes of Action Under Stress.
  7. Spermidine Attenuates Oxidative Stress-Induced Apoptosis via Blocking Ca2+ Overload in Retinal Pigment Epithelial Cells Independently of ROS.
  8. Involvement of Polyamine Metabolism in the Response of Medicago truncatula Genotypes to Salt Stress.
  9. Polyamine Metabolism Is Involved in the Direct Regeneration of Shoots from Arabidopsis Lateral Root Primordia.
  10. Effect of Methionine Restriction on Aging: Its Relationship to Oxidative Stress.
  11. Spermine and Spermidine Priming against Botrytis cinerea Modulates ROS Dynamics and Metabolism in Arabidopsis.
  1. Med Sci (Basel). 2021 Feb 05. pii: 8. [Epub ahead of print]9(1):
    Health-Promoting Effects of Dietary Polyamines.
    Rika Hirano, Hideto Shirasawa, Shin Kurihara.
      The purpose of this paper is to summarize the latest information on the various aspects of polyamines and their health benefits. In recent years, attempts to treat cancer by reducing elevated polyamines levels in cancer cells have been made, with some advancing to clinical trials. However, it has been reported since 2009 that polyamines extend the healthy life span of animals by inducing autophagy, protecting the kidneys and liver, improving cognitive function, and inhibiting the progression of heart diseases. As such, there is conflicting information regarding the relationship between polyamines and health. However, attempts to treat cancer by decreasing intracellular polyamines levels are a coping strategy to suppress the proliferation-promoting effects of polyamines, and a consensus is being reached that polyamine intake does not induce cancer in healthy individuals. To provide further scientific evidence for the health-promoting effects of polyamines, large-scale clinical studies involving multiple groups are expected in the future. It is also important to promote basic research on polyamine intake in animals, including elucidation of the polyamine balance between food, intestinal bacteria, and biosynthesis.
    Keywords:  food; health-promoting effect; intestinal bacteria; polyamines
    DOI:  https://doi.org/10.3390/medsci9010008
  2. Plant Physiol. 2021 Feb 12. pii: kiab062. [Epub ahead of print]
    Ornithine decarboxylase genes contribute to S-RNase-independent pollen rejection.
    Xiaoqiong Qin, Roger T Chetelat.
      Unilateral incompatibility (UI) manifests as pollen rejection in the pistil, typically when self-incompatible (SI) species are pollinated by self-compatible (SC) relatives. In the Solanaceae, UI occurs when pollen lack resistance to stylar S-RNases, but other, S-RNase-independent mechanisms exist. Pistils of the wild tomato Solanum pennellii LA0716 (SC) lack S-RNase yet reject cultivated tomato (S. lycopersicum, SC) pollen. In this cross, UI results from low pollen expression of a farnesyl pyrophosphate synthase gene (FPS2) in S. lycopersicum. Using pollen from fps2-/- loss-of-function mutants in S. pennellii, we identified a pistil factor locus, ui3.1, required for FPS2-based pollen rejection. We mapped ui3.1 to an interval containing 108 genes situated on the IL 3-3 introgression. This region includes a cluster of ornithine decarboxylase (ODC2) genes, with four copies in S. pennellii, versus one in S. lycopersicum. Expression of ODC2 transcript was 1034-fold higher in S. pennellii than in S. lycopersicum styles. Pistils of odc2-/-knockout mutants in IL 3-3 or S. pennellii fail to reject fps2 pollen and abolish transmission ratio distortion (TRD) associated with FPS2. Pollen of S. lycopersicum express low levels of FPS2 and are compatible on IL 3-3 pistils, but incompatible on IL 12-3 x IL 3-3 hybrids, which express both ODC2 and ui12.1, a locus thought to encode the SI proteins HT-A and HT-B. TRD observed in F2 IL 12-3 x IL 3-3 points to additional ODC2-interacting pollen factors on both chromosomes. Thus, ODC2 genes contribute to S-RNase independent UI and interact genetically with ui12.1 to strengthen pollen rejection.
    Keywords:  Solanum lycopersicum; Solanum pennellii; farnesyl pyrophosphate synthase; ornithine decarboxylase; unilateral incompatibility; unilateral incongruity
    DOI:  https://doi.org/10.1093/plphys/kiab062
  3. Nat Commun. 2021 Feb 12. 12(1): 971
    Dual targeting of polyamine synthesis and uptake in diffuse intrinsic pontine gliomas.
    Aaminah Khan, Laura D Gamble, Dannielle H Upton, Caitlin Ung, Denise M T Yu, Anahid Ehteda, Ruby Pandher, Chelsea Mayoh, Steven Hébert, Nada Jabado, Claudia L Kleinman, Mark R Burns, Murray D Norris, Michelle Haber, Maria Tsoli, David S Ziegler.
      Diffuse intrinsic pontine glioma (DIPG) is an incurable malignant childhood brain tumor, with no active systemic therapies and a 5-year survival of less than 1%. Polyamines are small organic polycations that are essential for DNA replication, translation and cell proliferation. Ornithine decarboxylase 1 (ODC1), the rate-limiting enzyme in polyamine synthesis, is irreversibly inhibited by difluoromethylornithine (DFMO). Herein we show that polyamine synthesis is upregulated in DIPG, leading to sensitivity to DFMO. DIPG cells compensate for ODC1 inhibition by upregulation of the polyamine transporter SLC3A2. Treatment with the polyamine transporter inhibitor AMXT 1501 reduces uptake of polyamines in DIPG cells, and co-administration of AMXT 1501 and DFMO leads to potent in vitro activity, and significant extension of survival in three aggressive DIPG orthotopic animal models. Collectively, these results demonstrate the potential of dual targeting of polyamine synthesis and uptake as a therapeutic strategy for incurable DIPG.
    DOI:  https://doi.org/10.1038/s41467-021-20896-z
  4. Int J Mol Sci. 2021 Jan 29. pii: 1376. [Epub ahead of print]22(3):
    Role of CgTpo4 in Polyamine and Antimicrobial Peptide Resistance: Determining Virulence in Candida glabrata.
    Mafalda Cavalheiro, Daniela Romão, Rui Santos, Dalila Mil-Homens, Pedro Pais, Catarina Costa, Mónica Galocha, Diana Pereira, Azusa Takahashi-Nakaguchi, Hiroji Chibana, Arsénio M Fialho, Miguel C Teixeira.
      Candida glabrata is an emerging fungal pathogen whose success depends on its ability to resist antifungal drugs but also to thrive against host defenses. In this study, the predicted multidrug transporter CgTpo4 (encoded by ORF CAGL0L10912g) is described as a new determinant of virulence in C. glabrata, using the infection model Galleria mellonella. The CgTPO4 gene was found to be required for the C. glabrata ability to kill G. mellonella. The transporter encoded by this gene is also necessary for antimicrobial peptide (AMP) resistance, specifically against histatin-5. Interestingly, G. mellonella's AMP expression was found to be strongly activated in response to C. glabrata infection, suggesting AMPs are a key antifungal defense. CgTpo4 was also found to be a plasma membrane exporter of polyamines, especially spermidine, suggesting that CgTpo4 is able to export polyamines and AMPs, thus conferring resistance to both stress agents. Altogether, this study presents the polyamine exporter CgTpo4 as a determinant of C. glabrata virulence, which acts by protecting the yeast cells from the overexpression of AMPs, deployed as a host defense mechanism.
    Keywords:  AMP resistance; Candida glabrata; CgTpo4; Galleria mellonella; polyamine resistance; virulence
    DOI:  https://doi.org/10.3390/ijms22031376
  5. Plant Signal Behav. 2021 Feb 12. 1885187
    A new insight into the contribution of putrescine to defense in Arabidopsis thaliana.
    Changxin Liu, Rubén Alcázar.
      Polyamines are known to accumulate in response to stress. Compelling evidence indicate a protective role for polyamines during defense. However, signaling pathways underlying polyamine functions have not been fully elucidated. We recently found that the polyamine putrescine (Put) accumulates during effector triggered immunity (ETI). Treatment with Put triggered local and systemic transcriptional reprogramming partly overlapping with systemic acquired resistance (SAR) responses. In addition, Put treatment led to local salicylic acid (SA) accumulation and systemic defenses against virulent bacteria. Consistent with this, we found that Put signaling is mainly ROS dependent and partly compromised by ENHANCED DISEASE SUSCEPTIBILITY1 (EDS1), SALICYLIC ACID INDUCTION DEFICIENT 2 (SID2) and NONEXPRESSOR of PR GENES1 (NPR1) loss-of-function mutations. Here, we propose a preliminary model by which putrescine contributes to local and systemic defenses in Arabidopsis thaliana.
    Keywords:  Polyamines; defense priming; plant defense; reactive oxygen species; salicylic acid; systemic acquired resistance
    DOI:  https://doi.org/10.1080/15592324.2021.1885187
  6. Front Plant Sci. 2020 ;11 616077
    Modulation of Ion Transport Across Plant Membranes by Polyamines: Understanding Specific Modes of Action Under Stress.
    Igor Pottosin, Miguel Olivas-Aguirre, Oxana Dobrovinskaya, Isaac Zepeda-Jazo, Sergey Shabala.
      This work critically discusses the direct and indirect effects of natural polyamines and their catabolites such as reactive oxygen species and γ-aminobutyric acid on the activity of key plant ion-transporting proteins such as plasma membrane H+ and Ca2+ ATPases and K+-selective and cation channels in the plasma membrane and tonoplast, in the context of their involvement in stress responses. Docking analysis predicts a distinct binding for putrescine and longer polyamines within the pore of the vacuolar TPC1/SV channel, one of the key determinants of the cell ionic homeostasis and signaling under stress conditions, and an additional site for spermine, which overlaps with the cytosolic regulatory Ca2+-binding site. Several unresolved problems are summarized, including the correct estimates of the subcellular levels of polyamines and their catabolites, their unexplored effects on nucleotide-gated and glutamate receptor channels of cell membranes and Ca2+-permeable and K+-selective channels in the membranes of plant mitochondria and chloroplasts, and pleiotropic mechanisms of polyamines' action on H+ and Ca2+ pumps.
    Keywords:  Ca2+ ATPase; H+-ATPase; TPC1; abiotic stress; ion channel; organelle; polyamines; vacuole
    DOI:  https://doi.org/10.3389/fpls.2020.616077
  7. Int J Mol Sci. 2021 Jan 29. pii: 1361. [Epub ahead of print]22(3):
    Spermidine Attenuates Oxidative Stress-Induced Apoptosis via Blocking Ca2+ Overload in Retinal Pigment Epithelial Cells Independently of ROS.
    Da Hye Kim, Jeong-Hwan Kim, Hyun Hwangbo, So Young Kim, Seon Yeong Ji, Min Yeong Kim, Hee-Jae Cha, Cheol Park, Su Hyun Hong, Gi-Young Kim, Seh-Kwang Park, Ji-Won Jeong, Mi-Young Kim, Yung Hyun Choi, Hyesook Lee.
      Retinal pigment epithelial (RPE) cells occupy the outer layer of the retina and perform various biological functions. Oxidative damage to RPE cells is a major risk factor for retinal degeneration that ultimately leads to vision loss. In this study, we investigated the role of spermidine in a hydrogen peroxide (H2O2)-induced oxidative stress model using human RPE cells. Our findings showed that 300 μM H2O2 increased cytotoxicity, apoptosis, and cell cycle arrest in the G2/M phase, whereas these effects were markedly suppressed by 10 μM spermidine. Furthermore, spermidine significantly reduced H2O2-induced mitochondrial dysfunction including mitochondrial membrane potential and mitochondrial activity. Although spermidine displays antioxidant properties, the generation of intracellular reactive oxygen species (ROS) upon H2O2 insult was not regulated by spermidine. Spermidine did suppress the increase in cytosolic Ca2+ levels resulting from endoplasmic reticulum stress in H2O2-stimulated human RPE cells. Treatment with a cytosolic Ca2+ chelator markedly reversed H2O2-induced cellular dysfunction. Overall, spermidine protected against H2O2-induced cellular damage by blocking the increase of intracellular Ca2+ independently of ROS. These results suggest that spermidine protects RPE cells from oxidative stress, which could be a useful treatment for retinal diseases.
    Keywords:  cytosolic Ca2+; endoplasmic reticulum stress; oxidative stress; retinal pigment epithelial (RPE) cells; spermidine
    DOI:  https://doi.org/10.3390/ijms22031361
  8. Plants (Basel). 2021 Jan 30. pii: 269. [Epub ahead of print]10(2):
    Involvement of Polyamine Metabolism in the Response of Medicago truncatula Genotypes to Salt Stress.
    Chrystalla Antoniou, Xavier Zarza, Gholamreza Gohari, Sima Panahirad, Panagiota Filippou, Antonio F Tiburcio, Vasileios Fotopoulos.
      Salinity constitutes one of the most important causes leading to severe reduction in plant yield. Several reports correlate the accumulation of polyamines in plants with tolerance to abiotic stress cues. The present study examined three Medicago truncatula genotypes with differing sensitivities to salinity (TN1.11, tolerant; Jemalong A17, moderately sensitive; TN6.18, sensitive), with the aim of examining the genotype-specific involvement of the polyamine metabolic pathway in plant response to salinity. The study was carried out with leaves harvested 48 h after watering plants with 200 mM NaCl. A comprehensive profile of free polyamines was determined using high performance liquid chromatography. All genotypes showed spermidine and spermine as the most abundant polyamines under control conditions. In salinity conditions, spermine levels increased at the expense of putrescine and spermidine, indicating a drift of polyamine metabolism towards the synthesis of increasing polycationic forms as a stress response. The increasing balance between high and low polycationic forms was clearly diminished in the salt-sensitive genotype TN6.18, showing a clear correlation with its sensitive phenotype. The polyamine metabolic profile was then supported by molecular evidence through the examination of polyamine metabolism transcript levels by RT-qPCR. General suppression of genes that are involved upstream in the PA biosynthetic pathway was determined. Contrarily, an induction in the expression of genes involved in the biosynthesis of spermine and spermidine was observed, in agreement with the metabolic analysis. A significant induction in diamino oxidase expression, involved in the catabolism of putrescine, was specifically found in the sensitive genotype ΤΝ6.18, indicating a distinct metabolic response to stress. Present findings highlight the involvement of polyamines in the defense response of Medicago genotypes showing sensitivity to salt stress.
    Keywords:  abiotic stress; gene expression; legumes; polyamines
    DOI:  https://doi.org/10.3390/plants10020269
  9. Plants (Basel). 2021 Feb 05. pii: 305. [Epub ahead of print]10(2):
    Polyamine Metabolism Is Involved in the Direct Regeneration of Shoots from Arabidopsis Lateral Root Primordia.
    Nikolett Kaszler, Péter Benkő, Dóra Bernula, Ágnes Szepesi, Attila Fehér, Katalin Gémes.
      Plants can be regenerated from various explants/tissues via de novo shoot meristem formation. Most of these regeneration pathways are indirect and involve callus formation. Besides plant hormones, the role of polyamines (PAs) has been implicated in these processes. Interestingly, the lateral root primordia (LRPs) of Arabidopsis can be directly converted to shoot meristems by exogenous cytokinin application. In this system, no callus formation takes place. We report that the level of PAs, especially that of spermidine (Spd), increased during meristem conversion and the application of exogenous Spd improved its efficiency. The high endogenous Spd level could be due to enhanced synthesis as indicated by the augmented relative expression of PA synthesis genes (AtADC1,2, AtSAMDC2,4, AtSPDS1,2) during the process. However, the effect of PAs on shoot meristem formation might also be dependent on their catabolism. The expression of Arabidopsis POLYAMINE OXIDASE 5 (AtPAO5) was shown to be specifically high during the process and its ectopic overexpression increased the LRP-to-shoot conversion efficiency. This was correlated with Spd accumulation in the roots and ROS accumulation in the converting LRPs. The potential ways how PAO5 may influence direct shoot organogenesis from Arabidopsis LRPs are discussed.
    Keywords:  Arabidopsis thaliana; direct shoot regeneration; hydrogen peroxide; polyamine oxidase; polyamines; reactive oxygen species; spermidine
    DOI:  https://doi.org/10.3390/plants10020305
  10. Biomedicines. 2021 Jan 29. pii: 130. [Epub ahead of print]9(2):
    Effect of Methionine Restriction on Aging: Its Relationship to Oxidative Stress.
    Munehiro Kitada, Yoshio Ogura, Itaru Monno, Jing Xu, Daisuke Koya.
      Enhanced oxidative stress is closely related to aging and impaired metabolic health and is influenced by diet-derived nutrients and energy. Recent studies have shown that methionine restriction (MetR) is related to longevity and metabolic health in organisms from yeast to rodents. The effect of MetR on lifespan extension and metabolic health is mediated partially through a reduction in oxidative stress. Methionine metabolism is involved in the supply of methyl donors such as S-adenosyl-methionine (SAM), glutathione synthesis and polyamine metabolism. SAM, a methionine metabolite, activates mechanistic target of rapamycin complex 1 and suppresses autophagy; therefore, MetR can induce autophagy. In the process of glutathione synthesis in methionine metabolism, hydrogen sulfide (H2S) is produced through cystathionine-β-synthase and cystathionine-γ-lyase; however, MetR can induce increased H2S production through this pathway. Similarly, MetR can increase the production of polyamines such as spermidine, which are involved in autophagy. In addition, MetR decreases oxidative stress by inhibiting reactive oxygen species production in mitochondria. Thus, MetR can attenuate oxidative stress through multiple mechanisms, consequently associating with lifespan extension and metabolic health. In this review, we summarize the current understanding of the effects of MetR on lifespan extension and metabolic health, focusing on the reduction in oxidative stress.
    Keywords:  autophagy; lifespan extension; metabolic health; methionine restriction; oxidative stress
    DOI:  https://doi.org/10.3390/biomedicines9020130
  11. Biomolecules. 2021 Feb 05. pii: 223. [Epub ahead of print]11(2):
    Spermine and Spermidine Priming against Botrytis cinerea Modulates ROS Dynamics and Metabolism in Arabidopsis.
    Henry Christopher Janse van Rensburg, Anis M Limami, Wim Van den Ende.
      Polyamines (PAs) are ubiquitous small aliphatic polycations important for growth, development, and environmental stress responses in plants. Here, we demonstrate that exogenous application of spermine (Spm) and spermidine (Spd) induced cell death at high concentrations, but primed resistance against the necrotrophic fungus Botrytis cinerea in Arabidopsis. At low concentrations, Spm was more effective than Spd. Treatments with higher exogenous Spd and Spm concentrations resulted in a biphasic endogenous PA accumulation. Exogenous Spm induced the accumulation of H2O2 after treatment but also after infection with B. cinerea. Both Spm and Spd induced the activities of catalase, ascorbate peroxidase, and guaiacol peroxidase after treatment but also after infection with B. cinerea. The soluble sugars glucose, fructose, and sucrose accumulated after treatment with high concentrations of PAs, whereas only Spm induced sugar accumulation after infection. Total and active nitrate reductase (NR) activities were inhibited by Spm treatment, whereas Spd inhibited active NR at low concentrations but promoted active NR at high concentrations. Finally, γaminobutyric acid accumulated after treatment and infection in plants treated with high concentrations of Spm. Phenylalanine and asparagine also accumulated after infection in plants treated with a high concentration of Spm. Our data illustrate that Spm and Spd are effective in priming resistance against B. cinerea, opening the door for the development of sustainable alternatives for chemical pesticides.
    Keywords:  Arabidopsis; B. cinerea; amino acids; polyamines; priming; reactive oxygen species; spermidine; spermine; sugars
    DOI:  https://doi.org/10.3390/biom11020223
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