bims-polyam Biomed News
on Polyamines
Issue of 2023–12–24
five papers selected by
Sebastian J. Hofer, University of Graz



  1. Iran J Pharm Res. 2023 Jan-Dec;22(1):22(1): e134938
      Polyamines prolong longevity due to their role in cell proliferation and are regarded as an essential group of anti-aging substances that reduce the risk of cardiovascular, neurological, and chronic inflammatory illnesses, as well as cancer. Because of its importance in growth and tissue regeneration, discovering polyamine-rich sources has gotten a lot of interest. Given the role of polyamines in controlling plant growth and physiological changes in the spring after cold winter stress, high polyamine concentrations in quickly growing plant tissues such as flowers, blossoms, and germs are possible. Based on this premise, five different spring flowers were selected and isolated from relevant plants, dried, and then quantified for the first time using an accurate, simple, and repeatable quantification method, liquid chromatography-tandem mass spectrometry. According to the amount of spermidine found in the samples investigated in this study, dried flower powders of Wisteria sinensis (244.18 µg/g), Lonicera caprifolium (217.28 µg/g), and Jasminum officinale (200.33 µg/g) appear to be a good source of spermidine. With additional research, W. sinensis dried flower powder is a good source of polyamines, whereas L. caprifolium and J. officinale dried flower powders are recommended as a rich source of spermidine for the preparation of natural supplements for people over the age of 30 to improve cell proliferation and anti-aging.
    Keywords:  LC-MS/MS; Polyamines; Spermidine; Spring Flowers
    DOI:  https://doi.org/10.5812/ijpr-134938
  2. Theriogenology. 2023 Dec 15. pii: S0093-691X(23)00497-1. [Epub ahead of print]215 290-301
      Spermidine, a natural polyamine, has been proven antioxidant function, but its pathway and mechanism of action remain unclear. Based on the oxidative stress model by 3-nitropropionic acid (3-NPA), the study explored the pathways by spermidine to rescue oxidative stress via autophagic process in goose granulosa cells by RNA-seq and RNA interference. In transcriptional regulation, in addition to KEGG pathways related to cell proliferation and differentiation, lots of KEGG pathways associated with inflammation, metabolism, and signaling were also significantly enriched in 3-NPA vs. 3-NPA + spermidine treatments. Six key genes (JUN, CD44, KITLG, RND2, BMP4 and KALRN) involved in spermidine-mediated anti-oxidative stress were screened. Furthermore, the experimental results showed that spermidine (80 μmol/L) significantly increased autophagic gene expression in goose granulosa cells, while EP300-siRNA or MAP1S-siRNA also significantly increased autophagic process. The autophagic gene expressions were no difference between EP300-siRNA and EP300-siRNA + spermidine treatments, although spermidine significantly increased autophagic process of granulosa cells compared to MAP1S-siRNA alone. In addition, inhibition of mTOR pathway significantly increased autophagic gene expression, which was further enhanced by spermidine in combined with mTOR inhibitor. These results suggest that spermidine can alleviate oxidative stress by inducing autophagy regulated by EP300, MAP1S and mTOR as well as regulating other independent gene expressions in goose granulosa cells.
    Keywords:  Antioxidant; Autophagy; Granulosa cells; Pathway; Spermidine
    DOI:  https://doi.org/10.1016/j.theriogenology.2023.12.020
  3. bioRxiv. 2023 Dec 09. pii: 2023.12.08.570828. [Epub ahead of print]
      The eukaryotic genome, first packed into nucleosomes of about 150 bp around the histone core, is organized into euchromatin and heterochromatin, corresponding to the A and B compartments, respectively. Here, we asked if individual nucleosomes in vivo know where to go. That is, do mono-nucleosomes by themselves contain A/B compartment information, associated with transcription activity, in their biophysical properties? We purified native mono-nucleosomes to high monodispersity and used physiological concentrations of biological polyamines to determine their condensability. The chromosomal regions known to partition into A compartments have low condensability and vice versa. In silico chromatin polymer simulations using condensability as the only input showed that biophysical information needed to form compartments is all contained in single native nucleosomes and no other factors are needed. Condensability is also strongly anticorrelated with gene expression, and especially so near the promoter region and in a cell type dependent manner. Therefore, individual nucleosomes in the promoter know whether the gene is on or off, and that information is contained in their biophysical properties. Comparison with genetic and epigenetic features suggest that nucleosome condensability is a very meaningful axis onto which to project the high dimensional cellular chromatin state. Analysis of condensability using various condensing agents including those that are protein-based suggests that genome organization principle encoded into individual nucleosomes is electrostatic in nature. Polyamine depletion in mouse T cells, by either knocking out ornithine decarboxylase (ODC) or inhibiting ODC, results in hyperpolarized condensability, suggesting that when cells cannot rely on polyamines to translate biophysical properties of nucleosomes to control gene expression and 3D genome organization, they accentuate condensability contrast, which may explain dysfunction known to occur with polyamine deficiency.
    DOI:  https://doi.org/10.1101/2023.12.08.570828
  4. Int J Mol Sci. 2023 Dec 09. pii: 17294. [Epub ahead of print]24(24):
      S-adenosylmethionine (SAM) is considered to be a useful therapeutic agent for degenerative cartilage diseases, although its mechanism is not clear. We previously found that polyamines stimulate the expression of differentiated phenotype of chondrocytes. We also found that the cellular communication network factor 2 (CCN2) played a huge role in the proliferation and differentiation of chondrocytes. Therefore, we hypothesized that polyamines and CCN2 could be involved in the chondroprotective action of SAM. In this study, we initially found that exogenous SAM enhanced proteoglycan production but not cell proliferation in human chondrocyte-like cell line-2/8 (HCS-2/8) cells. Moreover, SAM enhanced gene expression of cartilage-specific matrix (aggrecan and type II collagen), Sry-Box transcription factor 9 (SOX9), CCN2, and chondroitin sulfate biosynthetic enzymes. The blockade of the methionine adenosyltransferase 2A (MAT2A) enzyme catalyzing intracellular SAM biosynthesis restrained the effect of SAM on chondrocytes. The polyamine level in chondrocytes was higher in SAM-treated culture than control culture. Additionally, Alcian blue staining and RT-qPCR indicated that the effects of SAM on the production and gene expression of aggrecan were reduced by the inhibition of polyamine synthesis. These results suggest that the stimulation of polyamine synthesis and gene expression of chondrogenic differentiation factors, such as CCN2, account for the mechanism underlying the action of SAM on chondrocytes.
    Keywords:  CCN2; ODC; S-adenosylmethionine; chondrocyte differentiation; gene expression; polyamine
    DOI:  https://doi.org/10.3390/ijms242417294
  5. J Stroke Cerebrovasc Dis. 2023 Dec 14. pii: S1052-3057(23)00552-9. [Epub ahead of print]33(2): 107531
       OBJECTIVES: The role of urea cycle related amino acids in the development of ischemic stroke (IS) remains unclear. The study aimed to evaluate the association of these amino acids with IS.
    MATERIALS AND METHODS: We conducted a case-control study nested within a cohort study in Changshu, Eastern China. A total of 321 cases and 321 controls matched by age and gender were finally included. Plasma levels of ornithine, arginine, spermidine, and proline were measured using ultra-high performance liquid chromatography-tandem mass-spectrometry (UHPLC-MS/MS). Odds ratios (ORs) and their 95 % confidence intervals (CIs) were calculated by conditional logistic regression analyses.
    RESULTS: Plasma ornithine was inversely associated with risk of IS [crude OR: 0.62 (95 % CI: 0.40-0.97)]. After adjustment for body mass index, smoking, hypertension, family history of stroke, estimated glomerular filtration rate, and total cholesterol, the corresponding ORs for the highest compared to the lowest quartiles was essentially unchanged [adjusted OR: 0.62 (95 % CI: 0.39-0.99)]. The risk association remained significant after repeating the analyses by excluding the first two years of follow-up. Plasma arginine, spermidine, and proline were not associated with the risk of IS.
    CONCLUSION: We observed that higher plasma levels of ornithine were associated with a lower risk of incident IS. Our novel findings suggest a protective role of ornithine in the pathogenesis of IS.
    Keywords:  Amino acid; Ischemic stroke; Nested case-control study; Ornithine; Urea cycle
    DOI:  https://doi.org/10.1016/j.jstrokecerebrovasdis.2023.107531