bims-polyam Biomed News
on Polyamines
Issue of 2022–04–24
eight papers selected by
Sebastian J. Hofer, University of Graz
  1. Role of Polyamines and Hypusine in β Cells and Diabetes Pathogenesis.
  2. Putrescine Production by Latilactobacillus curvatus KP 3-4 Isolated from Fermented Foods.
  3. Unique Chemistry, Intake, and Metabolism of Polyamines in the Central Nervous System (CNS) and Its Body.
  4. Exogenously applied spermidine alleviates hypoxia stress in Phyllostachys praecox seedlings via changes in endogenous hormones and gene expression.
  5. Self-Assembled Alkylated Polyamine Analogs as Supramolecular Anticancer Agents.
  6. Spermidine Is an Intercellular Signal Modulating T3SS Expression in Pseudomonas aeruginosa.
  7. Development and characterization of rabbit monoclonal antibodies that recognize human spermine oxidase and application to immunohistochemistry of human cancer tissues.
  8. Polyamine Metabolites as Biomarkers in Head and Neck Cancer Biofluids.
  1. Metabolites. 2022 Apr 12. pii: 344. [Epub ahead of print]12(4):
    Role of Polyamines and Hypusine in β Cells and Diabetes Pathogenesis.
    Abhishek Kulkarni, Cara M Anderson, Raghavendra G Mirmira, Sarah A Tersey.
      The polyamines-putrescine, spermidine, and spermine-are polycationic, low molecular weight amines with cellular functions primarily related to mRNA translation and cell proliferation. Polyamines partly exert their effects via the hypusine pathway, wherein the polyamine spermidine provides the aminobutyl moiety to allow posttranslational modification of the translation factor eIF5A with the rare amino acid hypusine (hydroxy putrescine lysine). The "hypusinated" eIF5A (eIF5Ahyp) is considered to be the active form of the translation factor necessary for the translation of mRNAs associated with stress and inflammation. Recently, it has been demonstrated that activity of the polyamines-hypusine circuit in insulin-producing islet β cells contributes to diabetes pathogenesis under conditions of inflammation. Elevated levels of polyamines are reported in both exocrine and endocrine cells of the pancreas, which may contribute to endoplasmic reticulum stress, oxidative stress, inflammatory response, and autophagy. In this review, we have summarized the existing research on polyamine-hypusine metabolism in the context of β-cell function and diabetes pathogenesis.
    Keywords:  diabetes; eIF5A; hypusine; polyamines; putrescine; spermidine; spermine; β cells
    DOI:  https://doi.org/10.3390/metabo12040344
  2. Microorganisms. 2022 Mar 24. pii: 697. [Epub ahead of print]10(4):
    Putrescine Production by Latilactobacillus curvatus KP 3-4 Isolated from Fermented Foods.
    Rika Hirano, Aiko Kume, Chisato Nishiyama, Ryosuke Honda, Hideto Shirasawa, Yiwei Ling, Yuta Sugiyama, Misaki Nara, Hiromi Shimokawa, Hiroki Kawada, Takashi Koyanagi, Hisashi Ashida, Shujiro Okuda, Mitsuharu Matsumoto, Hiroki Takagi, Shin Kurihara.
      Polyamines are aliphatic hydrocarbons with terminal amino groups and are essential for biological activities. It has been reported that polyamines have health-promoting effects in animals, such as the extension of lifespan by polyamine intake. The identification of a high polyamine-producing bacterium from foods could lead to the development of a novel probiotic candidate. We aimed to identify high polyamine-producing bacteria from food, and isolated and collected bacteria from vegetables and fermented foods produced in Japan. We successfully acquired Latilactobacillus curvatus KP 3-4 isolated from Kabura-zushi as a putrescine producing lactic acid bacteria. Comparing the polyamine synthesis capability of L. curvatus KP 3-4 with that of typical probiotic lactic acid bacteria and L. curvatus strains available from the Japan Collection of Microorganisms, it was found that only L. curvatus KP 3-4 was capable of exporting high levels of putrescine into the culture supernatant. The enhancement of putrescine production by the addition of ornithine, and whole-genome analysis of L. curvatus KP 3-4, suggest that putrescine is synthesized via ornithine decarboxylase. The administration of L. curvatus KP 3-4 to germ-free mice increased the concentration of putrescine in the feces.
    Keywords:  lactic acid bacteria; polyamine; probiotics; whole-genome sequencing
    DOI:  https://doi.org/10.3390/microorganisms10040697
  3. Biomolecules. 2022 Mar 25. pii: 501. [Epub ahead of print]12(4):
    Unique Chemistry, Intake, and Metabolism of Polyamines in the Central Nervous System (CNS) and Its Body.
    Julian Rieck, Serguei N Skatchkov, Christian Derst, Misty J Eaton, Rüdiger W Veh.
      Polyamines (PAs) are small, versatile molecules with two or more nitrogen-containing positively charged groups and provide widespread biological functions. Most of these aspects are well known and covered by quite a number of excellent surveys. Here, the present review includes novel aspects and questions: (1) It summarizes the role of most natural and some important synthetic PAs. (2) It depicts PA uptake from nutrition and bacterial production in the intestinal system following loss of PAs via defecation. (3) It highlights the discrepancy between the high concentrations of PAs in the gut lumen and their low concentration in the blood plasma and cerebrospinal fluid, while concentrations in cellular cytoplasm are much higher. (4) The present review provides a novel and complete scheme for the biosynthesis of Pas, including glycine, glutamate, proline and others as PA precursors, and provides a hypothesis that the agmatine pathway may rescue putrescine production when ODC knockout seems to be lethal (solving the apparent contradiction in the literature). (5) It summarizes novel data on PA transport in brain glial cells explaining why these cells but not neurons preferentially accumulate PAs. (6) Finally, it provides a novel and complete scheme for PA interconversion, including hypusine, putreanine, and GABA (unique gliotransmitter) as end-products. Altogether, this review can serve as an updated contribution to understanding the PA mystery.
    Keywords:  CNS; agmatine; astrocytes; glial cells; neurons; nutrition; polyamines; spermidine; spermine; transport
    DOI:  https://doi.org/10.3390/biom12040501
  4. BMC Plant Biol. 2022 Apr 19. 22(1): 200
    Exogenously applied spermidine alleviates hypoxia stress in Phyllostachys praecox seedlings via changes in endogenous hormones and gene expression.
    Jianshuang Gao, Shunyao Zhuang, Yuhe Zhang, Zhuangzhuang Qian.
       BACKGROUND: Hypoxia stress is thought to be one of the major abiotic stresses that inhibits the growth and development of higher plants. Phyllostachys pracecox is sensitive to oxygen and suffers soil hypoxia during cultivation; however, the corresponding solutions to mitigate this stress are still limited in practice. In this study, Spermidine (Spd) was tested for regulating the growth of P. praecox seedlings under the hypoxia stress with flooding.
    RESULTS: A batch experiment was carried out in seedlings treated with 1 mM and 2 mM Spd under flooding for eight days. Application of 1 mM and 2 mM Spd could alleviate plant growth inhibition and reduce oxidative damage from hypoxia stress. Exogenous Spd significantly (P < 0.05) increased proline, soluble protein content, catalase (CAT), superoxide dismutase (SOD), and S-adenosylmethionine decarboxylase (SAMDC) activity, enhanced abscisic acid (ABA) and indole-3-acetic acid (IAA) content, and reduced ethylene emission, hydrogen peroxide (H2O2), superoxide radical (O2·-) production rate, ACC oxidase (ACO) and ACC synthase (ACS) to protect membranes from lipid peroxidation under flooding. Moreover, exogenous Spd up-regulated the expression of auxin-related genes auxin responsive factor1 (ARF1), auxin1 protein (AUX1), auxin2 protein (AUX2), auxin3 protein (AUX3) and auxin4 protein (AUX4), and down-regulated the expression of ethylene-related ACO and ACS genes during flooding.
    CONCLUSION: The results indicated that exogenous Spd altered hormone concentrations and the expression of hormone-related genes, thereby protecting the bamboo growth under flooding. Our data suggest that Spd can be used to reduce hypoxia-induced cell damage and improve the adaptability of P. praecox to flooding stress.
    Keywords:  Flooding; Gene expression; Hormone; Hypoxia; Phyllostachys praecox; Spermidine
    DOI:  https://doi.org/10.1186/s12870-022-03568-y
  5. Molecules. 2022 Apr 10. pii: 2441. [Epub ahead of print]27(8):
    Self-Assembled Alkylated Polyamine Analogs as Supramolecular Anticancer Agents.
    Diptesh Sil, Sudipta Panja, Chinmay M Jogdeo, Raj Kumar, Ao Yu, Cassandra E Holbert, Ling Ding, Jackson R Foley, Tracy Murray Stewart, Robert A Casero, David Oupický.
      Conformationally restrained polyamine analog PG11047 is a well-known drug candidate that modulates polyamine metabolism and inhibits cancer cell growth in a broad spectrum of cancers. Here, we report a structure-activity relationship study of the PG11047 analogs (HPGs) containing alkyl chains of varying length, while keeping the unsaturated spermine backbone unchanged. Synthesis of higher symmetrical homologues was achieved through a synthetic route with fewer steps than the previous route to PG11047. The amphiphilic HPG analogs underwent self-assembly and formed spherically shaped nanoparticles whose size increased with the hydrophobic alkyl group's increasing chain length. Assessment of the in vitro anticancer activity showed more than an eight-fold increase in the cancer cell inhibition activity of the analogs with longer alkyl chains compared to PG11047 in human colon cancer cell line HCT116, and a more than ten-fold increase in human lung cancer cell line A549. Evaluation of the inhibition of spermine oxidase (SMOX) showed no activity for PG11047, but activity was observed for its higher symmetrical homologues. Comparison with a reference SMOX inhibitor MDL72527 showed nine-fold better activity for the best performing HPG analog.
    Keywords:  PG11047; cancer therapy; polyamine analogs; self-assembly; spermine oxidase
    DOI:  https://doi.org/10.3390/molecules27082441
  6. Microbiol Spectr. 2022 Apr 18. e0064422
    Spermidine Is an Intercellular Signal Modulating T3SS Expression in Pseudomonas aeruginosa.
    Qiqi Lin, Huishan Wang, Jiahui Huang, Zhiqing Liu, Qunyi Chen, Guohui Yu, Zeling Xu, Ping Cheng, Zhibin Liang, Lian-Hui Zhang.
      Pseudomonas aeruginosa is a vital opportunistic human bacterial pathogen that causes acute and chronic infections. In this study, we set to determine whether the endogenous spermidine biosynthesis plays a role in regulation of type III secretion system (T3SS). The results showed that deletion of speA and speC, which encode putrescine biosynthesis, did not seem to affect cellular spermidine level and the T3SS gene expression. In contrast, mutation of speD and speE encoding spermidine biosynthesis led to significantly decreased spermidine production and expression of T3SS genes. We also showed that endogenous spermidine could auto-induce the transcriptional expression of speE and its full functionality required the transporter SpuDEFGH. Cytotoxicity analysis showed that mutants ΔspeE and ΔspuE were substantially attenuated in virulence compared with their wild-type strain PAO1. Our data imply a possibility that spermidine biosynthesis in P. aeruginosa may not use putrescine as a substrate, and that spermidine signaling pathway may interact with other two T3SS regulatory mechanisms in certain degree, i.e., cAMP-Vfr and GacS/GacA signaling systems. Taken together, these results specify the role of endogenous spermidine in regulation of T3SS in P. aeruginosa and provide useful clues for design and development antimicrobial therapies. IMPORTANCE Type III secretion system (T3SS) is one of the pivotal virulence factors of Pseudomonas aeruginosa responsible for evading phagocytosis, and secreting and translocating effectors into host cells. Previous studies underline the complicated and elaborate regulatory mechanisms of T3SS for the accurate, fast, and malicious pathogenicity of P. aeruginosa. Among these regulatory mechanisms, our previous study indicated that the spermidine from the host was vital to the host-pathogen interaction. However, the role of endogenous spermidine synthesized by P. aeruginosa on the regulation of T3SS expression is largely unknown. Here we reveal the role and regulatory network of endogenous spermidine synthesis in regulation of T3SS and bacterial virulence, showing that the spermidine is an important interspecies signal for modulating the virulence of P. aeruginosa through regulating T3SS expression.
    Keywords:  T3SS; exsCEBA; quorum sensing; regulation; spermidine
    DOI:  https://doi.org/10.1128/spectrum.00644-22
  7. PLoS One. 2022 ;17(4): e0267046
    Development and characterization of rabbit monoclonal antibodies that recognize human spermine oxidase and application to immunohistochemistry of human cancer tissues.
    Armand W J W Tepper, Gerald Chu, Vincent N A Klaren, Jay H Kalin, Patricia Molina-Ortiz, Antonietta Impagliazzo.
      The enzyme spermine oxidase (SMOX) is involved in polyamine catabolism and converts spermine to spermidine. The enzymatic reaction generates reactive hydrogen peroxide and aldehydes as by-products that can damage DNA and other biomolecules. Increased expression of SMOX is frequently found in lung, prostate, colon, stomach and liver cancer models, and the enzyme also appears to play a role in neuronal dysfunction and vascular retinopathy. Because of growing evidence that links SMOX activity with DNA damage, inflammation, and carcinogenesis, the enzyme has come into view as a potential drug target. A major challenge in cancer research is the lack of characterization of antibodies used for identification of target proteins. To overcome this limitation, we generated a panel of high-affinity rabbit monoclonal antibodies against various SMOX epitopes and selected antibodies for use in immunoblotting, SMOX quantification assays, immunofluorescence microscopy and immunohistochemistry. Immunohistochemistry analysis with the antibody SMAB10 in normal and transformed tissues confirms that SMOX is upregulated in several different cancers. Together, the panel of antibodies generated herein adds to the toolbox of high-quality reagents to study SMOX biology and to facilitate SMOX drug development.
    DOI:  https://doi.org/10.1371/journal.pone.0267046
  8. Diagnostics (Basel). 2022 Mar 24. pii: 797. [Epub ahead of print]12(4):
    Polyamine Metabolites as Biomarkers in Head and Neck Cancer Biofluids.
    Brian C DeFelice, Oliver Fiehn, Peter Belafsky, Constanze Ditterich, Michael Moore, Marianne Abouyared, Angela M Beliveau, D Gregory Farwell, Arnaud F Bewley, Shannon M Clayton, Joehleen A Archard, Jordan Pavlic, Shyam Rao, Maggie Kuhn, Peter Deng, Julian Halmai, Kyle D Fink, Andrew C Birkeland, Johnathon D Anderson.
      Background: Novel, non-invasive diagnostic biomarkers that facilitate early intervention in head and neck cancer are urgently needed. Polyamine metabolites have been observed to be elevated in numerous cancer types and correlated with poor prognosis. The aim of this study was to assess the concentration of polyamines in the saliva and urine from head and neck cancer (HNC) patients, compared to healthy controls. Methods: Targeted metabolomic analysis was performed on saliva and urine from 39 HNC patient samples and compared to 89 healthy controls using a quantitative, targeted liquid chromatography mass spectrometry approach. Results: The metabolites N1-acetylspermine (ASP), N8-acetylspermidine (ASD) and N1,N12-diacetylspermine (DAS) were detected at significantly different concentrations in the urine of HNC patients as compared to healthy controls. Only ASP was detected at elevated levels in HNC saliva as compared to healthy controls. Conclusion: These data suggest that assessment of polyamine-based metabolite biomarkers within the saliva and urine warrants further investigation as a potential diagnostic in HNC patients.
    Keywords:  biomarkers; head and neck cancer; metabolomics; polyamines; saliva; urine
    DOI:  https://doi.org/10.3390/diagnostics12040797
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