bims-polyam Biomed News
on Polyamines
Issue of 2022–02–13
seven papers selected by
Sebastian J. Hofer, University of Graz



  1. Cancer Control. 2021 Jan-Dec;28:28 10732748211039762
       BACKROUND: Polyamines play an important role in cellular proliferation, and the change in polyamine metabolism is reported in various cancers. We searched for urinary polyamine signature for distinguishing between pancreatic cancer, premalignant lesions of the pancreas (PLP), acute and chronic pancreatitis, and controls.
    METHODS: Patients and controls were prospectively recruited in three Finnish hospitals between October 2013 and June 2016. The patients provided a urine sample at the time of the diagnosis. The panel of 14 polyamines was obtained in a single run with mass spectrometry. The polyamine concentrations were analysed with quadratic discriminant analysis and cross-validated with leave-one-out cross-validation.
    RESULTS: Sixty-eight patients with pancreatic cancer, 36 with acute pancreatitis, 18 with chronic pancreatitis and 7 with PLP were recruited, as were 53 controls. The combination of 4 polyamines - acetylputrescine, diacetylspermidine, N8-acetylspermidine and diacetylputrescine - distinguished pancreatic cancer and PLP from controls (sensitivity = 94%, specificity = 68% and AUC = 0.88). The combination of diacetylspermidine, N8-acetylspermidine and diacetylspermine distinguished acute pancreatitis from controls (sensitivity = 94%, specificity = 92%, AUC = 0.98). The combination of acetylputrescine, diacetylspermidine and diacetylputrescine distinguished chronic pancreatitis from controls (sensitivity = 98%, specificity = 71%, AUC = 0.93).
    CONCLUSIONS: Optimally selected urinary polyamine panels discriminate between pancreatic cancer and controls, as well as between acute and chronic pancreatitis and controls.
    Keywords:  biomarker; pancreatic cancer; polyamines; quadratic discriminant analysis; urine VOCs
    DOI:  https://doi.org/10.1177/10732748211039762
  2. Funct Plant Biol. 2022 Feb 11.
      Plant leaves provide a unique insight into the changes that occur in organs, tissues and cells as they approach senescence. As part of the parental outlay, plants instigate leaf senescence to reallocate resources from older tissues to new organs towards the termination of the growing season. The aim of crop breeding initiatives is to optimize senescence for specific species. Considering hormonal regulation and their crosstalk during leaf senescence through integration of developmental signals, this work examines the efficacy of polyamines (PAs) in modulating several biochemical and physiological aspects with an ultimate aim to delay leaf senescence in leaf discs of Berginia ciliata (Haw.) sternb. Leaf discs were treated with putrescine (Put), spermidine (Spd) and spermine (Spm) at 20μM, 20μM and 15μM concentration, respectively. A set of leaf discs kept in distilled water served as the control. Leaf discs treated with PAs were green and fresh by about 4 days compared to the control, thus exhibited delayed senescence. This delayed leaf senescence corroborated with the maintenance of high activity of reactive oxygen species (ROS) scavenging antioxidant enzymes viz, superoxide dismutase (SOD), catalase (CAT), ascorbate peroxidase (APX) and higher content of chlorophylls. A marked increase was also observed in membrane stability and soluble proteins in leaf discs treated with PAs. Exogenous PAs reduced oxidative stress in the leaf discs, as revealed by lower malondialdehyde (MDA) level, which is manifested as reduced lipid peroxidation (LPO). Improved membrane stability was proportional to lower LPO, as measured by the membrane stability index (MSI).
    DOI:  https://doi.org/10.1071/FP21273
  3. Biochim Biophys Acta Mol Cell Res. 2022 Feb 07. pii: S0167-4889(22)00027-1. [Epub ahead of print] 119236
      Urea transporter B (UT-B, encoded by the SLC14A1 gene) is a membrane channel protein involved in urea transmembrane transport. Compared with normal tissues, UT-B expression is significantly decreased in most tumours, especially melanoma. However, the UT-B role in tumorigenesis and development is still unclear. Herein, we investigated the effects of UT-B overexpression on polyamine metabolism and the urea cycle in murine melanoma B16 cells, to explore the roles of mitochondrial dysfunction and p53 activation in cell growth and polyamines metabolism. UT-B overexpression in B16 cells decreased cell growth, increased apoptosis, and significantly altered metabolic pathways related to the urea cycle, which were characterized by reduced production of urea and polyamines and increased production of nitric oxide. Subsequently, we observed that activation of the p53 pathway may be the main cause of the above phenomena. The p53 inhibitor pifithrin-α partially restored the production of polyamines, but the mitochondrial morphology and function were still impaired. Further treatment of UT-B-overexpressing B16 cells with reactive oxygen species scavenging agent N-acetyl-l-cysteine and coenzyme Q10 restored cell viability and mitochondrial function and increased polyamine production. In conclusion, UT-B overexpression caused mitochondrial dysfunction and increased oxidative stress in B16 cells, and then activated p53 expression, which may be one of the mechanisms leading to the decrease in intracellular polyamines.
    Keywords:  Apoptosis; Melanoma; Mitochondrial dysfunction; Polyamine metabolism; p53
    DOI:  https://doi.org/10.1016/j.bbamcr.2022.119236
  4. Nat Prod Res. 2022 Feb 10. 1-6
      Caffeic acid (CA) is a naturally occurring plant-derived polyphenol possessing diverse biological properties. However, the poor water-solubility of CA restricts its widespread applications. On the other hand, biogenic amines such as spermine and spermidine are natural constituents in eukaryotes. In this work, we present water-soluble complexes of CA with spermine and spermidine by exploiting the acid-base interaction. Four different compositions have been prepared by varying the CA to amine ratios, whose chemical structures have been probed in detail using Fourier-transform infrared spectroscopy (FT-IR) and nuclear magnetic resonance (NMR) studies that have revealed the acid-base interaction between the constituent precursors. The obtained acid-base complexes at their native pH values have shown enhanced antibacterial and antioxidant activities than pristine CA. Further, the CA-polyamine complexes have shown high anticancer performances in the concentration range that is compatible with the normal cell lines.
    Keywords:  Caffeic acid; anticancer; antimicrobial; antioxidant; phytochemical; spermidine; spermine
    DOI:  https://doi.org/10.1080/14786419.2022.2038597
  5. Nucleic Acids Res. 2022 Feb 12. pii: gkac072. [Epub ahead of print]
      Ribosome assembly is an essential process that is linked to human congenital diseases and tumorigenesis. While great progress has been made in deciphering mechanisms governing ribosome biogenesis in eukaryotes, an inventory of factors that support ribosome synthesis in human cells is still missing, in particular regarding the maturation of the large 60S subunit. Here, we performed a genome-wide RNAi screen using an imaging-based, single cell assay to unravel the cellular machinery promoting 60S subunit assembly in human cells. Our screen identified a group of 310 high confidence factors. These highlight the conservation of the process across eukaryotes and reveal the intricate connectivity of 60S subunit maturation with other key cellular processes, including splicing, translation, protein degradation, chromatin organization and transcription. Intriguingly, we also identified a cluster of hits comprising metabolic enzymes of the polyamine synthesis pathway. We demonstrate that polyamines, which have long been used as buffer additives to support ribosome assembly in vitro, are required for 60S maturation in living cells. Perturbation of polyamine metabolism results in early defects in 60S but not 40S subunit maturation. Collectively, our data reveal a novel function for polyamines in living cells and provide a rich source for future studies on ribosome synthesis.
    DOI:  https://doi.org/10.1093/nar/gkac072
  6. J Genet Genomics. 2022 Feb 07. pii: S1673-8527(22)00036-4. [Epub ahead of print]
      Soil salinity inhibits seed germination and reduces seedling survival rate, resulting in significant yield reductions in crops. Here, we identified a polyamine oxidase, OsPAO3, conferring salt tolerance at the germination stage in rice (Oryza sativa L.), through map-based cloning approach. OsPAO3 is up-regulated under salt stress at the germination stage and highly expressed in various organs. Overexpression of OsPAO3 increased activity of polyamine oxidases, enhancing the polyamine content in seed coleoptiles. Increased polyamine may lead to the enhance of the activity of ROS-scavenging enzymes to eliminate over-accumulated H2O2 and the reduction of Na+ content in seed coleoptiles to maintain ion homeostasis and weaken Na+ damage. These changes resulted in stronger salt tolerance at the germination stage in rice. Our findings not only provide a novel gene for breeding new salt-tolerant rice cultivars but also help to elucidate the mechanism of salt tolerance in rice.
    Keywords:  Germination stage; OsPAO3; Polyamine oxidase; Rice; Salt tolerance
    DOI:  https://doi.org/10.1016/j.jgg.2022.01.007
  7. Colloids Surf B Biointerfaces. 2022 Feb 01. pii: S0927-7765(22)00062-5. [Epub ahead of print]212 112379
      A supramolecular strategy with sustainable emission amplification of an environmentally sensitive polyoxometalate, Na9[EuW10O36]·32H2O (EuW10), has been constructed for the Spm determination and discrimination. The EuW10 has no response to Put and other biogenic amine but a sensitive response to Spm (LOD = 0.56 nM) and Spd (LOD = 85.93 nM), respectively. Assembling with a cationic peptide from HPV E6, GL-22, achieved the EuW10/GL-22 assembly, which showed a unique enhanced emission response to Spm and distinguished it from Spd successfully. Furthermore, a synergistic rather than competitive binding of Spm to the EuW10/GL-22 assembly was revealed using FT-IR, and NMR titration spectra, together with DLS and TEM, essentially for the three-component sensing system. Besides, both EuW10 and EuW10/GL-22 assembly were successfully applied to the Spm determination in human urine and serum, suggesting the potential of these sensing approaches in detecting trace amounts of Spm in the clinic. Therefore, the constructed supramolecular assembly can detect the Spm sensitively (LOD = 2.0 nM) and efficiently distinguish it step-wise from other biogenic amines. It is a facile, straightforward, sensitive, and selective strategy for Spm determination and discrimination, which will be helpful in addressing the related biological and clinical requirements.
    Keywords:  Biogenic amines; Spermine discrimination & determination; Sustainable emission enhancement; Tri-assembly
    DOI:  https://doi.org/10.1016/j.colsurfb.2022.112379