bims-polyam Biomed News
on Polyamines
Issue of 2023–06–18
eleven papers selected by
Sebastian J. Hofer, University of Graz
  1. Spore-Forming Lactic Acid-Producing Bacterium Bacillus coagulans Synthesizes and Excretes Spermidine into the Extracellular Space.
  2. Levilactobacillus brevis with High Production of Putrescine Isolated from Blue Cheese and Its Application.
  3. Polyamine-Drug Conjugates: Do They Boost Drug Activity?
  4. Gut microbiota and anti-aging: Focusing on spermidine.
  5. Age-associated polyamines in peripheral blood cells and plasma in 20 to 70 years of age subjects.
  6. Synergistic effect of carbon nanoparticles with mild salinity for improving chemical composition and antioxidant activities of radish sprouts.
  7. An MYC-Driven Vicious Circuit Is a Targetable Achilles' Heel in Lymphoma.
  8. EPLIN-β is a novel substrate of ornithine decarboxylase antizyme 1 and mediates cellular migration.
  9. A polyamine acetyltransferase regulates the motility and biofilm formation of Acinetobacter baumannii.
  10. Barley HOMOCYSTEINE METHYLTRANSFERASE 2 confers drought tolerance by improving polyamine metabolism.
  11. Triptolide attenuates irritable bowel syndrome via inhibiting ODC1.
  1. J Agric Food Chem. 2023 Jun 14.
    Spore-Forming Lactic Acid-Producing Bacterium Bacillus coagulans Synthesizes and Excretes Spermidine into the Extracellular Space.
    Hideyuki Suzuki, Yuki Fujiwara, Kullathida Thongbhubate, Masahiro Maeda, Kenji Kanaori.
      The effect of spermidine in extending healthy longevity has attracted attention. As people age, their ability to synthesize putrescine, the precursor of spermidine, declines, and its supplementation from the diet or gut bacteria is needed. Many bacteria synthesize spermidine, but no strains have been reported to excrete de novo synthesized spermidine from the cells. We found that Bacillus coagulans strain YF1, isolated from "nanohana-duke", excreted de novo synthesized spermidine from the cells under anaerobic conditions. This strain synthesizes spermidine from arginine via agmatine, putrescine, and carboxyspermidine in sequential reactions, and the genes encoding the enzymes responsible for these reactions have been identified. B. coagulans is a gastric acid-resistant spore-forming lactic acid-producing bacterium, known for its beneficial effects as a probiotic. It can be used to produce lactic acid fermented foods containing spermidine. The newly discovered ability to excrete de novo synthesized spermidine is the decisive feature of this bacterium.
    Keywords:  carboxyspermidine; fermented food; longevity; nanohana-duke; polyamine; probiotics
    DOI:  https://doi.org/10.1021/acs.jafc.3c02184
  2. Int J Mol Sci. 2023 Jun 02. pii: 9668. [Epub ahead of print]24(11):
    Levilactobacillus brevis with High Production of Putrescine Isolated from Blue Cheese and Its Application.
    Yuta Ami, Narumi Kodama, Masahiro Umeda, Hanae Nakamura, Hideto Shirasawa, Takashi Koyanagi, Shin Kurihara.
      Polyamine intake has been reported to help extend the lifespan of animals. Fermented foods contain high concentrations of polyamines, produced by fermenting bacteria. Therefore, the bacteria, isolated from fermented foods that produce large amounts of polyamines, are potentially used as a source of polyamines for humans. In this study, the strain Levilactobacillus brevis FB215, which has the ability to accumulate approximately 200 µM of putrescine in the culture supernatant, was isolated from fermented foods, specifically the Blue Stilton cheese. Furthermore, L. brevis FB215 synthesized putrescine from agmatine and ornithine, which are known polyamine precursors. When cultured in the extract of Sakekasu, a byproduct obtained during the brewing of Japanese rice wine containing high levels of both agmatine and ornithine, L. brevis FB215 grew to OD600 = 1.7 after 83 h of cultivation and accumulated high concentrations (~1 mM) of putrescine in the culture supernatant. The fermentation product also did not contain histamine or tyramine. The Sakekasu-derived ingredient fermented by the food-derived lactic acid bacteria developed in this study could contribute to increasing polyamine intake in humans.
    Keywords:  Levilactobacillus brevis; blue cheese; food; polyamine; putrescine
    DOI:  https://doi.org/10.3390/ijms24119668
  3. Molecules. 2023 Jun 02. pii: 4518. [Epub ahead of print]28(11):
    Polyamine-Drug Conjugates: Do They Boost Drug Activity?
    Filippo Basagni, Giambattista Marotta, Michela Rosini, Anna Minarini.
      Over the past two decades, the strategy of conjugating polyamine tails with bioactive molecules such as anticancer and antimicrobial agents, as well as antioxidant and neuroprotective scaffolds, has been widely exploited to enhance their pharmacological profile. Polyamine transport is elevated in many pathological conditions, suggesting that the polyamine portion could improve cellular and subcellular uptake of the conjugate via the polyamine transporter system. In this review, we have presented a glimpse on the polyamine conjugate scenario, classified by therapeutic area, of the last decade with the aim of highlighting achievements and fostering future developments.
    Keywords:  antimicrobial; antitumor; drug conjugate; neuroprotective; polyamine
    DOI:  https://doi.org/10.3390/molecules28114518
  4. Crit Rev Food Sci Nutr. 2023 Jun 16. 1-19
    Gut microbiota and anti-aging: Focusing on spermidine.
    Leilei Yu, Jiani Pan, Min Guo, Hui Duan, Hao Zhang, Arjan Narbad, Qixiao Zhai, Fengwei Tian, Wei Chen.
      The human gut microbiota plays numerous roles in regulating host growth, the immune system, and metabolism. Age-related changes in the gut environment lead to chronic inflammation, metabolic dysfunction, and illness, which in turn affect aging and increase the risk of neurodegenerative disorders. Local immunity is also affected by changes in the gut environment. Polyamines are crucial for cell development, proliferation, and tissue regeneration. They regulate enzyme activity, bind to and stabilize DNA and RNA, have antioxidative properties, and are necessary for the control of translation. All living organisms contain the natural polyamine spermidine, which has anti-inflammatory and antioxidant properties. It can regulate protein expression, prolong life, and improve mitochondrial metabolic activity and respiration. Spermidine levels experience an age-related decrease, and the development of age-related diseases is correlated with decreased endogenous spermidine concentrations. As more than just a consequence, this review explores the connection between polyamine metabolism and aging and identifies advantageous bacteria for anti-aging and metabolites they produce. Further research is being conducted on probiotics and prebiotics that support the uptake and ingestion of spermidine from food extracts or stimulate the production of polyamines by gut microbiota. This provides a successful strategy to increase spermidine levels.
    Keywords:  Polyamines; aging; gut microbiota; probiotics; spermidine
    DOI:  https://doi.org/10.1080/10408398.2023.2224867
  5. Amino Acids. 2023 Jun 13.
    Age-associated polyamines in peripheral blood cells and plasma in 20 to 70 years of age subjects.
    Manuel Sánchez, Lorena Suárez, Gabriela Banda, Eva Barreiro-Alonso, Ignacio Rodríguez-Uña, José Manuel Rubín, Begoña Cantabrana.
      Dietary polyamines have been associated with slowing ageing processes and various pathologies, raising the importance of establishing reference values at different ages throughout life. This study aimed to analyse age-dependent variations in polyamine content using peripheral blood cells and plasma in a healthy and homogeneous population. Peripheral blood of 193 volunteers of both sexes (20-70 years), selected by convenience, was processed to separate cells and plasma. A pre-column derivatization method was used to determine the amines by HPLC (nmol or pmol/mg protein or nmol/ml) to analyse their association with the age (continuous or ordinal in decades) of the subjects. Putrescine and spermine weakly declined significantly in mononuclear cells with age. In erythrocytes and plasma, putrescine showed an evident decrease in the 60-70-year-old group compared to the rest. The ratios between polyamines, mainly in erythrocytes, decreased in the 60-70 years age group and increased the ratio of putrescine in mononuclear cells/erythrocytes. The ratio of putrescine in mononuclear cells/erythrocytes was higher in the 60-70-year-old age group than in the rest. In a sample of subjects (20-29 vs. 60-70 years), whole blood polyamines were not significantly different when differences existed in erythrocytes. Polyamine homeostasis in blood cells and plasma changed with age. Putrescine declined in mononuclear cells and decreased in erythrocytes and plasma in the decade of the 60 s. Further studies should establish an age-dependent phenotype and whether polyamines' supplementation could restore the decreased values and be associated with long-term overall biological benefits.
    Keywords:  Age; Human peripheral blood; Polyamines; Putrescine; Spermidine; Spermine
    DOI:  https://doi.org/10.1007/s00726-023-03269-2
  6. Front Plant Sci. 2023 ;14 1158031
    Synergistic effect of carbon nanoparticles with mild salinity for improving chemical composition and antioxidant activities of radish sprouts.
    Riyadh F Halawani, Hamada AbdElgawad, Fahed A Aloufi, Mansour A Balkhyour, Ahlem Zrig, Abdelrahim H A Hassan.
      The demand for healthy foods with high functional value has progressively increased. Carbon nanoparticles (CNPs) have a promising application in agriculture including the enhancement of plant growth. However, there are few studies on the interactive effects of CNPs and mild salinity on radish seed sprouting. To this end, the effect of radish seed priming with 80mM CNPs on biomass, anthocyanin, proline and polyamine metabolism, and antioxidant defense system under mild salinity growth condition (25 mM NaCl). The results indicated that seed nanopriming with CNPs along with mild salinity stress enhanced radish seed sprouting and its antioxidant capacity. Priming boosted the antioxidant capacity by increasing antioxidant metabolites such as (polyphenols, flavonoids, polyamines, anthocyanin, and proline). To understand the bases of these increases, precursors and key biosynthetic enzymes of anthocyanin [phenylalanine, cinnamic acid, coumaric acid, naringenin, phenylalanine ammonia lyase, chalcone synthase (CHS), cinnamate-4-hydroxylase (C4H) and 4-coumarate: CoA ligase (4CL)], proline [pyrroline-5-carboxylate synthase (P5CS), proline dehydrogenase (PRODH), Sucrose, Sucrose P synthase, invertase) and polyamines [putrescine, spermine, spermidine, total polyamines, arginine decarboxylase, orinthnine decarboxylase, S-adenosyl-L-methionine decarboxylase, spermidine synthase, spermine synthase] were analyzed. In conclusion, seed priming with CNPs has the potential to further stimulate mild salinity-induced bioactive compound accumulation in radish sprouts.
    Keywords:  anthocyanin; carbon nanoparticles; mild salinity; polyamines; proline; radish sprouts
    DOI:  https://doi.org/10.3389/fpls.2023.1158031
  7. Blood Cancer Discov. 2023 Jun 14. OF1-OF4
    An MYC-Driven Vicious Circuit Is a Targetable Achilles' Heel in Lymphoma.
    Erica B Wilson, Ulf Klein.
       SUMMARY: In this issue of Blood Cancer Discovery, Nakanishi et al. uncover a critical role for the elevated activity of the translation initiation factor eIF5A in the malignant growth of MYC-driven lymphoma. eIF5A is posttranslationally modified by hypusination through MYC oncoprotein-mediated hyperactivation of the polyamine-hypusine circuit, which may represent a promising therapeutic target because an enzyme of this circuit that is required for hypusinating eIF5A proved to be essential for lymphoma development. See related article by Nakanishi et al. (4).
    DOI:  https://doi.org/10.1158/2643-3230.BCD-23-0053
  8. J Cell Sci. 2023 Jun 15. pii: jcs260427. [Epub ahead of print]136(12):
    EPLIN-β is a novel substrate of ornithine decarboxylase antizyme 1 and mediates cellular migration.
    Dan Li, Suat Peng Neo, Jayantha Gunaratne, Kanaga Sabapathy.
      Polyamines promote cellular proliferation. Their levels are controlled by ornithine decarboxylase antizyme 1 (Az1, encoded by OAZ1), through the proteasome-mediated, ubiquitin-independent degradation of ornithine decarboxylase (ODC), the rate-limiting enzyme of polyamine biosynthesis. Az1-mediated degradation of other substrates such as cyclin D1 (CCND1), DNp73 (TP73) or Mps1 regulates cell growth and centrosome amplification, and the currently known six Az1 substrates are all linked with tumorigenesis. To understand whether Az1-mediated protein degradation might play a role in regulating other cellular processes associated with tumorigenesis, we employed quantitative proteomics to identify novel Az1 substrates. Here, we describe the identification of LIM domain and actin-binding protein 1 (LIMA1), also known as epithelial protein lost in neoplasm (EPLIN), as a new Az1 target. Interestingly, between the two EPLIN isoforms (α and β), only EPLIN-β is a substrate of Az1. The interaction between EPLIN-β and Az1 appears to be indirect, and EPLIN-β is degraded by Az1 in a ubiquitination-independent manner. Az1 absence leads to elevated EPLIN-β levels, causing enhanced cellular migration. Consistently, higher LIMA1 levels correlate with poorer overall survival of colorectal cancer patients. Overall, this study identifies EPLIN-β as a novel Az1 substrate regulating cellular migration.
    Keywords:  Antizyme; Cell migration; EPLIN; Polyamines; Ubiquitin-independent degradation
    DOI:  https://doi.org/10.1242/jcs.260427
  9. Nat Commun. 2023 Jun 14. 14(1): 3531
    A polyamine acetyltransferase regulates the motility and biofilm formation of Acinetobacter baumannii.
    Julija Armalytė, Albinas Čepauskas, Gabija Šakalytė, Julius Martinkus, Jūratė Skerniškytė, Chloé Martens, Edita Sužiedėlienė, Abel Garcia-Pino, Dukas Jurėnas.
      Acinetobacter baumannii is a nosocomial pathogen highly resistant to environmental changes and antimicrobial treatments. Regulation of cellular motility and biofilm formation is important for its virulence, although it is poorly described at the molecular level. It has been previously reported that Acinetobacter genus specifically produces a small positively charged metabolite, polyamine 1,3-diaminopropane, that has been associated with cell motility and virulence. Here we show that A. baumannii encodes novel acetyltransferase, Dpa, that acetylates 1,3-diaminopropane, directly affecting the bacterium motility. Expression of dpa increases in bacteria that form pellicle and adhere to eukaryotic cells as compared to planktonic bacterial cells, suggesting that cell motility is linked to the pool of non-modified 1,3-diaminopropane. Indeed, deletion of dpa hinders biofilm formation and increases twitching motion confirming the impact of balancing the levels of 1,3-diaminopropane on cell motility. The crystal structure of Dpa reveals topological and functional differences from other bacterial polyamine acetyltransferases, adopting a β-swapped quaternary arrangement similar to that of eukaryotic polyamine acetyltransferases with a central size exclusion channel that sieves through the cellular polyamine pool. The structure of catalytically impaired DpaY128F in complex with the reaction product shows that binding and orientation of the polyamine substrates are conserved between different polyamine-acetyltransferases.
    DOI:  https://doi.org/10.1038/s41467-023-39316-5
  10. Plant Physiol. 2023 Jun 10. pii: kiad333. [Epub ahead of print]
    Barley HOMOCYSTEINE METHYLTRANSFERASE 2 confers drought tolerance by improving polyamine metabolism.
    Cheng-Wei Qiu, Ma Yue, Qing-Qing Wang, Man-Man Fu, Chengdao Li, Yizhou Wang, Feibo Wu.
      Drought stress poses a serious threat to crop production worldwide. Genes encoding homocysteine methyltransferase (HMT) have been identified in some plant species in response to abiotic stress, but its molecular mechanism in plant drought tolerance remains unclear. Here, transcriptional profiling, evolutionary bioinformatics, and population genetics were conducted to obtain insight into the involvement of HvHMT2 from Tibetan wild barley (Hordeum vulgare ssp. agriocrithon) in drought tolerance. We then performed genetic transformation coupled with physio-biochemical dissection and comparative multi-omics approaches to determine the function of this protein and the underlying mechanism of HvHMT2-mediated drought tolerance. HvHMT2 expression was strongly induced by drought stress in tolerant genotypes in a natural Tibetan wild barley population and contributed to drought tolerance through S-adenosylmethionine (SAM) metabolism. Overexpression of HvHMT2 promoted HMT synthesis and efficiency of the SAM cycle, leading to enhanced drought tolerance in barley through increased endogenous spermine and less oxidative damage and growth inhibition, thus improving water status and final yield. Disruption of HvHMT2 expression led to hypersensitivity under drought treatment. Application of exogenous spermine reduced accumulation of reactive oxygen species (ROS), which was increased by exogenous mitoguazone (inhibitor of spermine biosynthesis), consistent with the association of HvHMT2-mediated spermine metabolism and ROS scavenging in drought adaptation. Our findings reveal the positive role and key molecular mechanism of HvHMT2 in drought tolerance in plants, providing a valuable gene not only for breeding drought-tolerant barley cultivars but also for facilitating breeding schemes in other crops in a changing global climate.
    Keywords:  ROS scavenging; Tibetan wild barley (Hordeum vulgare ssp agriocrithon); drought stress; homocysteine S-methyltransferase (HMT); spermine metabolism
    DOI:  https://doi.org/10.1093/plphys/kiad333
  11. BMC Gastroenterol. 2023 Jun 12. 23(1): 202
    Triptolide attenuates irritable bowel syndrome via inhibiting ODC1.
    Ning Zhu, Liuyan Zhu, Xueliang Zhang, Chengbin Huang, Wenjun Xiang, Bingwu Huang.
       BACKGROUND: Irritable bowel syndrome (IBS) is a chronic disorder of the gut-brain axis with significant morbidity. Triptolide, an active compound extracted from Tripterygium wilfordii Hook F (TwHF), has been widely used as a major medicinal herb in the treatment of inflammatory disease.
    METHODS: The chronic-acute combined stress (CAS) stimulation was used to establish IBS rat model. The model rats were then gavaged with triptolide. Forced swimming, marble-burying, fecal weight and abdominal withdrawal reflex (AWR) score were recorded. Pathologic changes in the ileal and colonic tissues were validated by hematoxylin and eosin staining. The inflammatory cytokines and Ornithine Decarboxylase-1 (ODC1) in the ileal and colonic tissues were performed by ELISA and WB.
    RESULTS: Triptolide didn't have antidepressant- and antianxiety- effects in rats caused by CAS, but decreased fecal weight and AWR score. In addition, Triptolide reduced the release of IL-1, IL-6, and TNF-α and the expression of ODC1 in the ileum and colon.
    CONCLUSION: The therapeutic efficacy of triptolide for IBS induced by CAS was revealed in this study, which may be related to the reduction of ODC1.
    Keywords:  Inflammation; Irritable bowel syndrome; Ornithine decarboxylase 1; Triptolide
    DOI:  https://doi.org/10.1186/s12876-023-02847-8
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