bims-polyam Biomed News
on Polyamines
Issue of 2024–12–22
seven papers selected by
Sebastian J. Hofer, University of Graz
  1. Exploring polyamine metabolism of the yeast-like fungus, Emergomyces africanus.
  2. Hypusination in intestinal epithelial cells protects mice from infectious colitis.
  3. Spermidine alleviates depression via control of the stress response.
  4. Polyamine Seed Priming: A Way to Enhance Stress Tolerance in Plants.
  5. Polyamines Protect Porcine Sperm from Lipopolysaccharide-induced Mitochondrial Dysfunction and Apoptosis via Casein Kinase 2 Activation.
  6. Deciphering the Interplay between G-quadruplexes and natural/synthetic polyamines.
  7. Prognostic, oncogenic roles, and pharmacogenomic features of AMD1 in hepatocellular carcinoma.
  1. FEMS Yeast Res. 2024 Jan 09. pii: foae038. [Epub ahead of print]24
    Exploring polyamine metabolism of the yeast-like fungus, Emergomyces africanus.
    Elizaveta Koroleva, Barbra Toplis, Malcolm Taylor, Corné van Deventer, Heidi C Steffen, Christiaan van den Heever, Nelesh P Govender, Sybren de Hoog, Alfred Botha.
      Emergomyces africanus is a thermally dimorphic pathogen causing severe morbidity and mortality in immunocompromized patients. Its transition to a pathogenic yeast-like phase in the human host is a notable virulence mechanism. Recent studies suggest polyamines as key players in dimorphic switching, yet their precise functions remain enigmatic. This work aimed to explore polyamine metabolism of two clinical strains of E. africanus (CBS 136260 and CBS 140360) in mycelial and yeast-like phases. In this first report of the polyamine profile of E. africanus, we reveal, using mass spectrometry, spermidine, and spermine as the major polyamines in both phases. The secretion of these amines was significantly higher in the pathogenic yeast-like phase than in the mycelial phase, warranting further investigation into the implications thereof on virulence. Additionally, we detected the activity of several polyamine biosynthesis enzymes, including arginine decarboxylase, agmatinase, arginase, and ornithine decarboxylase, with significant differences in enzyme expression between morphological phases and strains. Finally, we provide initial evidence for the requirement for spermine, spermidine, and putrescine during the thermally induced dimorphic switch of E. africanus, with strain-specific differences in the production of these amines. Overall, our study presents novel insight into polyamine metabolism and its role in dimorphism of E. africanus.
    Keywords:   Emergomyces africanus ; dimorphism; ornithine decarboxylase; polyamine biosynthesis; spermine
    DOI:  https://doi.org/10.1093/femsyr/foae038
  2. Gut Microbes. 2024 Jan-Dec;16(1):16(1): 2438828
    Hypusination in intestinal epithelial cells protects mice from infectious colitis.
    Alain P Gobert, Caroline V Hawkins, Kamery J Williams, Lydia A Snyder, Daniel P Barry, Mohammad Asim, Margaret M Allaman, Kara M McNamara, Alberto G Delgado, Yu Wang, Shilin Zhao, Kristie L Rose, M Blanca Piazuelo, Keith T Wilson.
      Enteropathogenic Escherichia coli (EPEC) is a bacterium that causes attaching/effacing (A/E) lesions and serious diarrheal disease, a major health issue in developing countries. EPEC pathogenicity results from the effect of virulence factors and dysregulation of host responses. Polyamines, including spermidine, play a major role in intestinal homeostasis. Spermidine is the substrate for deoxyhypusine synthase (DHPS), which catalyzes the conjugation of the amino acid hypusine to eukaryotic translation initiation factor 5A (EIF5A); hypusinated EIF5A (EIF5AHyp) binds specific mRNAs and initiates translation. Our aim was to determine the role of hypusination during infection with A/E pathogens. We found that DHPS and EIF5AHyp levels are induced in i) a colonic epithelial cell line and human-derived colon organoids infected with EPEC, and ii) the colon of mice infected with Citrobacter rodentium, the rodent equivalent of EPEC. Specific deletion of Dhps in intestinal epithelial cells worsened clinical, histological, and pro-inflammatory parameters in C. rodentium-infected mice. These animals also exhibited an exacerbated pathogenic transcriptome in their colon. Furthermore, infected mice with specific Dhps deletion exhibited reduced levels of proteins involved in detoxification of tissue-damaging reactive aldehydes and consequently increased electrophile adducts in the colon. Thus, hypusination in intestinal epithelial cells protects from infectious colitis mediated by A/E pathogens.
    Keywords:  Citrobacter rodentium; Enteropathogenic Escherichia coli; Polyamines; attaching and effacing pathogen; colitis; host–pathogen interactions; hypusine; mucosal immune response; translation
    DOI:  https://doi.org/10.1080/19490976.2024.2438828
  3. bioRxiv. 2024 Dec 07. pii: 2024.12.04.626625. [Epub ahead of print]
    Spermidine alleviates depression via control of the stress response.
    Sarah Mackert, Christine Niemeyer, Yara Mecdad, Tim Ebert, Thomas Bajaj, Sylvère Durand, Sebastian J Hofer, Andreas Zellner, Bianca Besteher, Jan Engelmann, Barbara Gisabella, Valerie Kempf, Lily A Heckmann, Marcel Laakmann, Emily L Newman, Clara Sokn, Daniel E Heinz, Ellen Junglas, Andrés Uribe-Marino, Christoph Magnes, Claudia Klengel, Anna Müller, Lydia Opriessnig, Andreas Meinitzer, Martina Lennarz, Katja M Wirtz Martin, Rawan Albatarni, Marieke Brockherde, Klaus Lieb, Henrik Rohner, Birgit Stoffel-Wagner, Alexandra Philipsen, Bernhard Kuster, Markus Kölle, Kerry J Ressler, Nils Opel, Mathias V Schmidt, Harry Pantazopoulos, Marianne B Müller, Guido Kroemer, Tobias Eisenberg, Jakob Hartmann, Frank Madeo, Nils C Gassen.
      Depression is a stress-associated disorder, and it represents a major global health issue. Its pathophysiology is complex and remains insufficiently understood, with current medications often showing limited efficacy and undesirable side effects. Here, we identify imbalanced polyamine levels and dysregulated autophagy as key components of the acute stress response in humans, and as hallmarks of chronic stress and depressive disorders. Moreover, conventional antidepressant pharmacotherapy increases endogenous plasma concentrations of the polyamine spermidine exclusively in patients who respond to the treatment, suggesting a link between spermidine and successful outcomes. In a clinical trial, involving drug-naive depressed individuals, three weeks of spermidine supplementation increased autophagy and alleviated symptoms of depression. Behavioral and mechanistic findings of spermidine supplementation were validated in various mouse stress and depression models. In summary, spermidine supplementation mitigates polyamine dysregulation and stimulates autophagy under pathological stress conditions, offering a novel and well-tolerated treatment approach for stress-related depressive disorders.
    DOI:  https://doi.org/10.1101/2024.12.04.626625
  4. Int J Mol Sci. 2024 Nov 23. pii: 12588. [Epub ahead of print]25(23):
    Polyamine Seed Priming: A Way to Enhance Stress Tolerance in Plants.
    Łukasz Wojtyla, Karolina Wleklik, Sławomir Borek, Małgorzata Garnczarska.
      Polyamines (PAs), such as putrescine, spermine, and spermidine, are bioactive molecules that play a vital role in plant responses to stresses. Although they are frequently applied to achieve higher levels of stress tolerance in plants, their function in seed biology is still not fully understood. PAs have been described in only a limited number of studies as seed priming agents, but most of the data report only the physiological and biochemical PA effects, and only a few reports concern the molecular mechanisms. In this review, we summarized PA seed priming effects on germination, seedling establishment, and young plant response to abiotic stresses, and tried to draw a general scheme of PA action during early developmental plant stages.
    Keywords:  abiotic stress; chilling stress; priming memory; rice (Oryza sativa L.); salt stress; seed biology; seed germination
    DOI:  https://doi.org/10.3390/ijms252312588
  5. J Anim Sci. 2024 Dec 20. pii: skae383. [Epub ahead of print]
    Polyamines Protect Porcine Sperm from Lipopolysaccharide-induced Mitochondrial Dysfunction and Apoptosis via Casein Kinase 2 Activation.
    Rongnan Li, Xiaodong Wu, Jia Chen, Zhendong Zhu, Ming Guo, Guochao Hou, Tianjiao Li, Yi Zheng, Haidong Ma, Hongzhao Lu, Wenxian Zeng, Tao Zhang, Xiaoxu Chen.
      Bacterial contamination is an inevitable issue during the processing of semen preservation in pigs. As a prototypical endotoxin from Gram-negative bacteria in semen, lipopolysaccharide (LPS) undermines sperm function during liquid preservation. Spermine and spermidine could protect cells against LPS-induced injury, and the content of spermine and spermidine in seminal plasma is positively correlated with sperm quality. Thus, the present study aimed to clarify whether addition of spermine or spermidine is beneficial to porcine semen preservation and able to prevent LPS-induced sperm damage. The supplementation of spermine and spermidine in the diluent resulted in higher sperm motility, viability, acrosome integrity, and mitochondrial membrane potential (ΔΨm) after preservation in vitro at 17 °C for 7 d (P < 0.05). LPS induced sperm quality deterioration, ΔΨm decline, cellular adenosine-triphosphate (ATP) depletion, mitochondrial ultrastructure abnormality, mitochondrial permeability transition pore (MPTP) opening, phosphatidylserine (PS) translocation, and caspase-3 activation (P < 0.05). Interestingly, spermine and spermidine alleviated the LPS-induced changes of the aforementioned parameters and mitigated the decrease in the microtubule-associated protein light chain 3-II (LC3-II) to LC3-I ratio. Meanwhile, the α and β subunits of casein kinase 2 (CK2) were detected at the connecting piece and the tail. Significantly, addition of 4,5,6,7-tetrabromobenzotriazole (TBB), a specific CK2 inhibitor, counteracted the beneficial effects of spermine and spermidine on sperm quality, mitochondrial activity, and apoptosis. Together, these results suggest that spermine and spermidine improve sperm quality and the efficiency of liquid preservation of porcine semen. Furthermore, spermine and spermidine alleviate LPS-induced sperm mitochondrial dysfunction and apoptosis in a CK2-dependent manner.
    Keywords:  casein kinase 2; lipopolysaccharide; mitochondria; polyamines; sperm
    DOI:  https://doi.org/10.1093/jas/skae383
  6. Chembiochem. 2024 Dec 10. e202400873
    Deciphering the Interplay between G-quadruplexes and natural/synthetic polyamines.
    Ariadna Gil-Martinez, Cristina Galiana-Rosello, Andrea Lázaro-Gómez, Laura Mulet-Rivero, Jorge Gonzalez-Garcia.
      The interplay between polyamines and G-quadruplexes has been largely overlooked in the literature, even though polyamines are ubiquitous metabolites in living cells and G-quadruplexes are transient regulatory elements, being both of them key regulators of biological processes. Herein, we compile the investigations connecting G-quadruplexes and biogenic polyamines to understand the biological interplay between them. Moreover, we overview the main works focused on synthetic ligands containing polyamines designed to target G-quadruplexes, aiming to unravel the structural motifs for designing potent and selective G4 ligands.
    Keywords:  polyamine - G-quadruplex - G4 binder - ligand - macrocycle - cryptand
    DOI:  https://doi.org/10.1002/cbic.202400873
  7. Cancer Cell Int. 2024 Dec 18. 24(1): 398
    Prognostic, oncogenic roles, and pharmacogenomic features of AMD1 in hepatocellular carcinoma.
    Youliang Zhou, Yi Zhou, Jiabin Hu, Yao Xiao, Yan Zhou, Liping Yu.
       BACKGROUND: AMD1 is the gene encoding S-adenosylmethionine decarboxylase 1. How AMD1 affects the prognosis of hepatocellular carcinoma (HCC) patients is unclear.
    METHODS: Using the Cancer Genome Atlas (TCGA) liver hepatocellular carcinoma datasets, gene enrichment and immunological traits were compared between groups with high and low AMD1 expression. After altering AMD1 expression in HCC cells, cell viability, the clonal formation rate, and migration and invasion ability were detected. Univariate Cox regression analysis and Pearson correlation were used to screen for AMD1-related genes (ARGs). Multidimensional bioinformatic algorithms were utilized to establish a risk score model for ARGs.
    RESULTS: AMD1 expression was notably increased in the majority of cancer types. High AMD1 expression was associated with adverse outcomes and poorer immunotherapy response in HCC patients. AMD1 exhibited higher expression levels in HCC cell lines. The efficient inhibition of HCC cell proliferation, migration, and invasion in vitro can be achieved through the downregulation of AMD1. The AMD1-related risk score was constructed with the expression of 9 ARGs, and demonstrated high predictive efficacy in multiple validation cohorts. Patients with high risk scores exhibited greater resistance to classical chemotherapy drugs. The nomogram, which consists of age, stage, and the AMD1-related risk score, was used to calculate the probability of survival for each individual.
    CONCLUSION: The present study indicates that AMD1 functions as a potential role in HCC progression and may serve as a therapeutic target in HCC. This study constructed a novel AMD1-related scoring system for predicting the prognosis and treatment responsiveness of patients with HCC, enabling the prediction of prognosis and identification of potential treatment targets.
    Keywords:  Hepatocellular carcinoma; Polyamine; Prognosis; S-adenosylmethionine decarboxylase 1; Treatment responsiveness
    DOI:  https://doi.org/10.1186/s12935-024-03593-x
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