bims-polyam Biomed News
on Polyamines
Issue of 2024–08–18
seven papers selected by
Sebastian J. Hofer, University of Graz
  1. The Synergistic Benefit of Combination Strategies Targeting Tumor Cell Polyamine Homeostasis.
  2. Involvement of mammalian SoLute Carriers (SLC) in the traffic of polyamines.
  3. The Many Faces of Hypusinated eIF5A: Cell Context-Specific Effects of the Hypusine Circuit and Implications for Human Health.
  4. Pillar[n]arene-Based Fluorescence Turn-On Chemosensors for the Detection of Spermine, Spermidine, and Cadaverine in Saline Media and Biofluids.
  5. Influence of Some Heterocyclic, Cyclic, and Nitrogen-Containing Compounds on Oxidative Deamination of Polyamines in a Cell-Free Test System.
  6. Physiological responses and microbiota shifts after spermidine administration as a postbiotic on rodents fed a high-fat high-fructose diet.
  7. Spermine and spermidine SI-PPCs: Molecular dynamics reveals enhanced biomolecular interactions.
  1. Int J Mol Sci. 2024 Jul 26. pii: 8173. [Epub ahead of print]25(15):
    The Synergistic Benefit of Combination Strategies Targeting Tumor Cell Polyamine Homeostasis.
    Ting-Ann Liu, Tracy Murray Stewart, Robert A Casero.
      Mammalian polyamines, including putrescine, spermidine, and spermine, are positively charged amines that are essential for all living cells including neoplastic cells. An increasing understanding of polyamine metabolism, its molecular functions, and its role in cancer has led to the interest in targeting polyamine metabolism as an anticancer strategy, as the metabolism of polyamines is frequently dysregulated in neoplastic disease. In addition, due to compensatory mechanisms, combination therapies are clinically more promising, as agents can work synergistically to achieve an effect beyond that of each strategy as a single agent. In this article, the nature of polyamines, their association with carcinogenesis, and the potential use of targeting polyamine metabolism in treating and preventing cancer as well as combination therapies are described. The goal is to review the latest strategies for targeting polyamine metabolism, highlighting new avenues for exploiting aberrant polyamine homeostasis for anticancer therapy and the mechanisms behind them.
    Keywords:  polyamine; polyamine analogues; polyamine biosynthesis; polyamine biosynthesis inhibitors; polyamine catabolism; polyamine combination therapeutic strategies; polyamine transport
    DOI:  https://doi.org/10.3390/ijms25158173
  2. Front Mol Biosci. 2024 ;11 1452184
    Involvement of mammalian SoLute Carriers (SLC) in the traffic of polyamines.
    Lorena Pochini.
      Polyamines interact with different molecular targets to regulate a vast range of cellular processes. A network of enzymes and transport systems is crucial for the maintenance of polyamine homeostasis. Indeed, polyamines after synthesis must be distributed to the various tissues and some intracellular organelles. Differently from the well characterized enzymes devoted to polyamine synthesis, the transport systems are not unequivocally identified or characterized. Besides some ATPases which have been identified as polyamine transporters, much less is known about solute carriers (SLC) involved in the transport of these compounds. Only two SLCs have been unequivocally identified as polyamine transporters: SLC18B1 (VPAT) and SLC22A4 (OCTN1). Transport studies have been performed with cells transfected with the cDNAs encoding the two and other SLCs or, in the case of OCTN1, also by in vitro assay using proteoliposomes harboring the recombinant human protein. According to the role proposed for OCTN1, polyamines have been associated with prolonged and quality of life. This review provides an update on the most recent findings concerning the polyamine transporters or the prediction of the putative ones.
    Keywords:  OCTN1; SLC18B1; SLC22A4; cancer; neuronal disorders; putrescine; spermidine; spermine
    DOI:  https://doi.org/10.3389/fmolb.2024.1452184
  3. Int J Mol Sci. 2024 Jul 26. pii: 8171. [Epub ahead of print]25(15):
    The Many Faces of Hypusinated eIF5A: Cell Context-Specific Effects of the Hypusine Circuit and Implications for Human Health.
    Shima Nakanishi, John L Cleveland.
      The unique amino acid hypusine [Nε-(4-amino-2-hydroxybutyl)lysine] is exclusively formed on the translational regulator eukaryotic initiation factor 5A (eIF5A) via a process coined hypusination. Hypusination is mediated by two enzymes, deoxyhypusine synthase (DHPS) and deoxyhypusine hydroxylase (DOHH), and hypusinated eIF5A (eIF5AHyp) promotes translation elongation by alleviating ribosome pauses at amino acid motifs that cause structural constraints, and it also facilitates translation initiation and termination. Accordingly, eIF5AHyp has diverse biological functions that rely on translational control of its targets. Homozygous deletion of Eif5a, Dhps, or Dohh in mice leads to embryonic lethality, and heterozygous germline variants in EIF5A and biallelic variants in DHPS and DOHH are associated with rare inherited neurodevelopmental disorders, underscoring the importance of the hypusine circuit for embryonic and neuronal development. Given the pleiotropic effects of eIF5AHyp, a detailed understanding of the cell context-specific intrinsic roles of eIF5AHyp and of the chronic versus acute effects of eIF5AHyp inhibition is necessary to develop future strategies for eIF5AHyp-targeted therapy to treat various human health problems. Here, we review the most recent studies documenting the intrinsic roles of eIF5AHyp in different tissues/cell types under normal or pathophysiological conditions and discuss these unique aspects of eIF5AHyp-dependent translational control.
    Keywords:  DHPS; DOHH; aging; cancer; eIF5A; hypusine; immune senescence; metabolism; polyamine; spermidine
    DOI:  https://doi.org/10.3390/ijms25158171
  4. Chemistry. 2024 Aug 14. e202401071
    Pillar[n]arene-Based Fluorescence Turn-On Chemosensors for the Detection of Spermine, Spermidine, and Cadaverine in Saline Media and Biofluids.
    Amrutha Prabodh, Laura M Grimm, Pronay Kumar Biswas, Vahideh Mahram, Frank Biedermann.
      Polyamines are essential analytes due to their critical role in various biological processes and human health in general. Due to their role as regulators for cell growth and proliferation (putrescine and spermine), as neuroprotectors, gero-, and cardiovascular protectors (spermidine), and as bacterial growth indicators (cadaverine), rapid, simple, and cost-effective methods for polyamine detection in biofluids are in demand. The present study focuses on the development and investigation of self-assembled and fluorescent host⋅dye chemo-sensors based on sulfonated pillar[5]arene for the specific detection of polyamines. Binding studies, as well as stability and functionality assessments of the turn-on chemosensors for selective polyamine detection in saline and biologically relevant media, are shown. Furthermore, the practical applicability of the developed chemo-sensors is demonstrated in biofluids such as human urine and saliva.
    Keywords:  Biofluid; Fluorescence detection; Host-guest chemistry; Pillararene; Polyamine sensing
    DOI:  https://doi.org/10.1002/chem.202401071
  5. Bull Exp Biol Med. 2024 Aug 10.
    Influence of Some Heterocyclic, Cyclic, and Nitrogen-Containing Compounds on Oxidative Deamination of Polyamines in a Cell-Free Test System.
    S P Syatkin, M L Blagonravov, A Hilal, K Yu Sungrapova, R I Sokuev, I A Korzun, V A Goryachev.
      We studied the effects of some nitrogen-containing, heterocyclic, and cyclic compounds on the rate of oxidative deamination of polyamines and putrescine in tissues with a high proliferation rate. For this purpose, the specific activities of the main enzymes of polyamine oxidative degradation - spermine oxidase (SMO), polyamine oxidase (PAO), and diamine oxidase (DAO) were determined using a cell-free test system from regenerating rat liver. The compounds methyl 2-(5-formylfuran-2-yl)benzoate and 2,7-bis-[2-(diethylamino)ethoxy]-9H-fluoren-9-one (and in the form of dihydrochloride) showed mainly activating effect on oxidative degradation of putrescine, spermidine, and spermine, which indirectly indicates their antiproliferative effect. Nitrogen-free compounds inhibited this process, thus exhibiting potentially carcinogenic properties. Correlations were calculated for activity of DAO, PAO, and SMO with 5 topological indices: Wiener (W), Rouvray (R), Balaban (J) in the Trinaistich modification, detour (Ip), and electropy (Ie). The highest dependence was noted for DAO and the Balaban index (R=-0.55), for PAO and the detour index (R=0.78), and for SMO and the electropy index (R=0.53). The remaining dependencies showed insignificant correlation strength.
    Keywords:  diamine oxidase; heterocyclic compounds; polyamine oxidase; polyamines; spermine oxidase
    DOI:  https://doi.org/10.1007/s10517-024-06179-9
  6. Benef Microbes. 2024 Aug 14. 1-11
    Physiological responses and microbiota shifts after spermidine administration as a postbiotic on rodents fed a high-fat high-fructose diet.
    N C O Melo, A Cuevas-Sierra, A Casillas-Fikentscher, L Arellano-Garcia, M P Portillo, I Milton-Laskibar, J A Martinez.
      The consumption of a high-fat high-fructose diet partly resemble the western dietary patterns, which is closely associated with excessive body adiposity and metabolic disorders, such as obesity and type 2 diabetes. Moreover, this unhealthy regime produces unfavourable changes on the faecal microbiota, potentially interfering with microorganisms postbiotic function, such as spermidine, a natural polyamine that has been involved in the control of weight gain. The study aimed to analyse the repercussions of spermidine supplementation on somatic measurements, metabolic markers, and the faecal microbiota profile of rats fed a diet rich in fat and fructose. Indeed, Wistar males with oral administration of spermidine (20 mg/kg/day) for 6 weeks were evaluated for food and energy intake, biochemical markers, and faecal microbiota signatures. The daily use of spermidine decreased weight gain ( P < 0.01), reduced feed efficiency ( P < 0.01), and attenuated visceral fat deposition ( P < 0.01), although no effect on energy intake, hepatic weight, triglyceride and glucose index and atherogenic indexes. Similarly, the consumption of spermidine partially restored the presence of microbial species, notably Akkermansia muciniphila. Elevated concentrations of this species were linked to a decrease in triglycerides ( P = 0.04), indicating that the supplementation of spermidine might contribute to managing energy fuel homeostasis in association with an obesogenic diet.
    DOI:  https://doi.org/10.1163/18762891-bja00029
  7. Int J Biol Macromol. 2024 Aug 10. pii: S0141-8130(24)05459-X. [Epub ahead of print]278(Pt 1): 134654
    Spermine and spermidine SI-PPCs: Molecular dynamics reveals enhanced biomolecular interactions.
    Frederico Henrique do C Ferreira, Nicholas P Farrell, Luiz Antônio S Costa.
      In this paper the effects on the interaction of highly positively charged substitution-inert platinum polynuclear complexes (SI-PPCs) with negatively charged DNA and heparin are examined and compared by theoretical chemistry methods. Electrostatic and hydrogen bonding interactions contribute to the overall effects on the biomolecule. Root Mean Square (RMS) deviation, Solvent Accessible Surface, RMS fluctuation, and interaction analysis all confirm similar effects on both biomolecules, dictated predominantly by the total positive charge and total number of hydrogen bonds formed. Especially, changes in structural parameters suggesting condensation and reduction of available surface area will reduce or prevent normal protein recognition and may thus potentially inhibit biological mechanisms related to apoptosis (DNA) or reduced vascularization viability (HEP). Thermodynamic analyses supported these findings with favourable interaction energies. The comparison of DNA and heparin confirms the general intersectionality between the two biomolecules and confirms the intrinsic dual-nature function of this chemotype. The distinction between the two-limiting mode of actions (HS or DNA-centred) could reflect an intriguing balance between extracellular (GAG) and intracellular (DNA) binding and affinities. The results underline the need to fully understand GAG-small molecule interactions and their contribution to drug pharmacology and related therapeutic modalities. This report contributes to that understanding.
    Keywords:  Noncovalent interactions; Polyamines; Polynuclear platinum complexes
    DOI:  https://doi.org/10.1016/j.ijbiomac.2024.134654
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