bims-polyam Biomed News
on Polyamines
Issue of 2021–01–03
ten papers selected by
Sebastian J. Hofer, University of Graz



  1. Anim Nutr. 2020 Dec;6(4): 438-446
      l-proline (Pro) is a precursor of ornithine, which is converted into polyamines via ornithine decarboxylase (ODC). Polyamines plays a key role in the proliferation of intestinal epithelial cells. The study investigated the effect of Pro on polyamine metabolism and cell proliferation on porcine enterocytes in vivo and in vitro. Twenty-four Huanjiang mini-pigs were randomly assigned into 1 of 3 groups and fed a basal diet that contained 0.77% alanine (Ala, iso-nitrogenous control), 1% Pro or 1% Pro + 0.0167% α-difluoromethylornithine (DFMO) from d 15 to 70 of gestation. The fetal body weight and number of fetuses per litter were determined, and the small and large intestines were obtained on d 70 ± 1.78 of gestation. The in vitro study was performed in intestinal porcine epithelial (IPEC-J2) cells cultured in Dulbecco's modified Eagle medium-high glucose (DMEM-H) containing 0 μmol/L Pro, 400 μmol/L Pro, or 400 μmol/L Pro + 10 mmol/L DFMO for 4 d. The results showed that maternal dietary supplementation with 1% Pro increased fetal weight; the protein and DNA concentrations of the fetal small intestine; and mRNA levels for potassium voltage-gated channel, shaker-related subfamily, member 1 (Kv1.1) in the fetal small and large intestines (P < 0.05). Supplementing Pro to either gilts or IPEC-J2 cells increased ODC protein abundances and polyamine concentrations in the fetal intestines and IPEC-J2 cells (P < 0.05). In comparison with the Pro group, the combined administration of Pro and DFMO reduced the expression of ODC protein and spermine concentration in the fetal intestine, as well as the concentrations of putrescine, spermidine and spermine in IPEC-J2 cells (P < 0.05). Meanwhile, the percentage of cells in the S-phase and the mRNA levels of proto-oncogenes c-fos and c-myc were increased in response to Pro supplementation, whereas depletion of cellular polyamines with DFMO increased tumor protein p53 (p53) mRNA levels (P < 0.05). Taken together, dietary supplementation with Pro improved fetal pig growth and intestinal epithelial cell proliferation via enhancing polyamine synthesis.
    Keywords:  Intestine; Ornithine decarboxylase; Pig; Polyamine metabolism; l-proline; α-difluoromethylornithine
    DOI:  https://doi.org/10.1016/j.aninu.2020.07.001
  2. Talanta. 2021 Mar 01. pii: S0039-9140(20)31081-X. [Epub ahead of print]224 121790
      Bioactive polyamines play important roles in many biological processes such as gene expression, cell growth, protein synthesis, and signal transduction. Accurate determination of polyamines is helpful for studying their biological functions. Herein, a C60-based chemical labeling strategy was proposed for the determination of polyamines (putrescine, cadaverine, spermidine, and spermine) in biological samples using matrix-assisted laser desorption/ionization mass spectrometry (MALDI MS). An N-hydroxysuccinimide ester functionalized C60 (NHS-C60) was used as a labeling reagent and the m/z of the labeled polyamines reached up to more than 900 Da, which avoided matrix interferences in the low m/z region. In addition, as NHS-C60 derivatives, mono- and bis-substituted polyamines were produced simultaneously, which benefited the qualitative analysis of polyamines. The analytical method was validated using NHS-C60 labeled polyamines in cells and mice feces samples. Good linearities were obtained with correlation coefficients ranging from 0.9786 to 0.9982. The limits of quantification were in the range of 0.68-1.48 pmol. Good reproducibility and reliability of our proposed method were confirmed by intra- and inter-day precisions ranged from 2.8 to 16.6%, and the recoveries ranged between 81.8 and 119.9%. Finally, the proposed method was applied to determine polyamines in cells and mice feces. Three polyamines were detected in the cells, and the contents of cadaverine and spermidine in the feces of high-fat diet mice were found to be significantly lower than those in the normal diet mice. The results show that the proposed NHS-C60 labeling coupled with MALDI MS strategy is suitable for the determination of polyamines in biological samples.
    Keywords:  Cells; Chemical labeling; MALDI MS; NHS–C(60); Polyamines
    DOI:  https://doi.org/10.1016/j.talanta.2020.121790
  3. Talanta. 2021 Mar 01. pii: S0039-9140(20)31159-0. [Epub ahead of print]224 121868
      Metabolites of methionine cycle, urea cycle and polyamine metabolism play important roles in regulating the metabolic processes and the development of diseases. It is rewarding and interesting to monitor the levels of the above metabolites in biological matrices to investigate pathological mechanisms. However, their quantitation is still unsatisfactory due to the poor retention behavior of the analytes on the traditional reversed-phase column. And never a single analytical method simultaneously quantify these three classes of metabolites. Besides, the concentrations of some metabolites are too low to be detected in the biological samples. In this study, we developed a UHPLC-ESI-MS/MS method to simultaneously determine the levels of 14 metabolites, including 4 methionine metabolism metabolites (methionine, homocysteine, S-adenosylmethionine and S-adenosylhomocysteine), 3 urea cycle intermediates (arginine, citrulline and ornithine) and 7 polyamines (putrescine, spermidine, spermine, N1-acetylputrescine, N1-acetylspermidine, N1-acetylspermine and N1,N12-diacetylspermine). The chromatographic separation was performed on the BEH amide column within 14 min using water and acetonitrile (both with 0.1% formic acid) as the mobile phases. The results of method validation showed good selectivity, linearity (r2 > 0.99), recovery (93.1%-112.1%), inter-day and intra-day precision (RSD < 13.6% and RSD < 11.0%, respectively), stability (RSD < 15.1%) and matrix effect (76.0%-113.2%). The method is simple, quick and sensitive without derivatization processes and the use of ion-pairing reagents. This approach was successfully applied in urine, serum and tissue matrices, as well as in identifying potential biomarkers for hyperthyroidism and hypothyroidism. The method is promising to provide more information on pathophysiological mechanisms in metabolomics study.
    Keywords:  Biological matrices; Methionine cycle metabolites; Polyamines; Thyroid disorder; UHPLC-MS/MS; Urea cycle intermediates
    DOI:  https://doi.org/10.1016/j.talanta.2020.121868
  4. J Agric Food Chem. 2020 Dec 24.
      Spermidine is a biologically active polyamine with extensive application potential in functional foods. However, previously reported spermidine titers by biosynthesis methods are relatively low, which hinders its industrial application. To improve the spermidine titer, key genes affecting the spermidine production were mined to modify Bacillus amyloliquefaciens. Genes of S-adenosylmethionine decarboxylase (speD) and spermidine synthase (speE) from different microorganisms were expressed and compared in B. amyloliquefaciens. Therein, the speD from Escherichia coli and speE from Saccharomyces cerevisiae were confirmed to be optimal for spermidine synthesis, respectively. Gene and amino acid sequence analysis further confirmed the function of speD and speE. Then, these two genes were co-expressed to generate a recombinant strain B. amyloliquefaciens HSAM2(PDspeD-SspeE) with a spermidine titer of 105.2 mg/L, improving by 11.0-fold compared with the control (HSAM2). Through optimization of the fermentation medium, the spermidine titer was increased to 227.4 mg/L, which was the highest titer among present reports. Moreover, the consumption of the substrate S-adenosylmethionine was consistent with the accumulation of spermidine, which contributed to understanding its synthesis pattern. In conclusion, two critical genes for spermidine synthesis were obtained, and an engineering B. amyloliquefaciens strain was constructed for enhanced spermidine production.
    Keywords:  Bacillus amyloliquefaciens; combined expression; gene mining; sequence analysis; spermidine
    DOI:  https://doi.org/10.1021/acs.jafc.0c07143
  5. Chemosphere. 2020 Dec 22. pii: S0045-6535(20)33598-0. [Epub ahead of print]269 129400
      Carcass decomposition could be considered as a common phenomenon in nature. However, during degradation processes, animal carcasses produce many toxic and harmful metabolites, posing potential ecological risks to water safety, thereby threatening human health. However, the metabolites produced by decomposition of animal corpses are not well understood. In this study, building on our previous baseline study of microbial community between the experimental groups (with animal carcasses) and control groups (without carcasses), the samples at the ultimate stage (19th day) of carcass decomposition were chosen to investigate the metabolic profiles and uncover the relationships between water quality, microbes and noxious metabolites in two types of water (Yellow River water and tap water) using fish as animal model by widely targeted metabolomics. Our results showed amino acid metabolomics, indole and its derivatives, and pyridine and pyridine derivatives mainly occurred in the corpse groups, suggesting that these metabolites are markers of carcass decomposition. And some noxious metabolites (e.g., polyamine, amines, and benzene and substituted derivatives) highly associated with carcass decomposition, which revealed new insights into how to investigate the hazard materials in water. And these noxious metabolites in the corpse groups were even increased 214543-fold in average compared with the control groups. Meanwhile, treatment was the most important factor affecting the water metabolites while microbiome contributed a small proportion to the metabolic profiles. Several opportunistic pathogenic genera Comamonas, Bacteriodes and Alcaligenes co-occurred most frequently with several kinds of polyamines and amines while some dominant genera Rhodoferax, Delftia and Brevundimonas had significant positive relationships with specific benzene and substituted derivatives. This work demonstrates that carcass decomposition causes water quality deterioration by producing various toxic metabolites, thus providing new insights into noxious metabolites when exposed to animal carcasses in aquatic environment.
    Keywords:  Amines; Carcass; Metabolic profiles; Microbiome; Polyamines
    DOI:  https://doi.org/10.1016/j.chemosphere.2020.129400
  6. Foods. 2020 Dec 24. pii: E30. [Epub ahead of print]10(1):
      In the last decades, cauliflower consumption has increased due to its observed beneficial effects on human health, especially on chronic diseases. Furthermore, the use of arginine has been shown to improve the heat stress tolerance of plants by increasing the polyamine content. Thus, we aimed to investigate the effects of the exogenous application of arginine on the physical and chemical quality parameters of cauliflower florets under heat stress. For this, we applied two concentrations of arginine (1 and 4 mM) to the leaves of cauliflower (Brassica oleracea var. botrytis L.) plants grown in three different temperatures (ambient, elevated, and extreme). Our data show that potassium and phosphate, as well as iron were the most abundant macro- and micronutrients, respectively. The combination of high temperature and exogenous application of arginine increased the antioxidant activity, total content of phenolic compounds, polyamines, and proteins. The data presented herein indicate that the combination of an adequate heat stress and the appropriate foliar arginine treatment may be a useful strategy that could be used to increase the number of valuable plant compounds in our diet.
    Keywords:  Brassica oleracea var. botrytis L.; UHPLC-DAD; antioxidants; exogenous arginine; polyamines; short-term heat stress
    DOI:  https://doi.org/10.3390/foods10010030
  7. Bioresour Technol. 2020 Dec 15. pii: S0960-8524(20)31816-2. [Epub ahead of print]323 124542
      Modern chemical industry calls for new resource-efficient and sustainable value chains for production of key base chemicals such as polyamines. The green microalga Chlamydomonas reinhardtii offers great potential as an innovative green-cell factory by combining fast and inexpensive, phototrophic growth with mature genetic engineering. Here, overexpression of recombinant lysine decarboxylases in C. reinhardtii enabled the robust accumulation of the non-native polyamine cadaverine, which serves as building block for bio-polyamides. The issue of low cell densities, limiting most microalgal cultivation processes was resolved by systematically optimizing cultivation parameters. A new, easy-to-apply and fully phototrophic medium enables high cell density cultivations of C. reinhardtii with a 6-fold increase in biomass and cell count (20 g/L biomass dry weight, ~2·108 cells/mL). Application of high cell density cultivations in established photobioreactors resulted in a 10-fold increase of cadaverine yields, with up to 0.24 g/L after 9 days and maximal productivity of 0.1 g/L/d.
    Keywords:  Cadaverine; Chlamydomonas reinhardtii; High cell density; Medium optimization; Microalgae; Polyamine
    DOI:  https://doi.org/10.1016/j.biortech.2020.124542
  8. J Chromatogr B Analyt Technol Biomed Life Sci. 2020 Nov 30. pii: S1570-0232(20)31344-1. [Epub ahead of print]1162 122468
       BACKGROUND: Many scientific contributions recognize polyamines as important biomarkers for the diagnosis and treatment of cancer. Several authors have suggested the use of LC/MS instruments as an elective method for their measurement, providing good detection limits and specificity; however, many of these procedures suffer from long chromatographic run times, high detection limits and lengthy and expensive sample pre-treatment steps.
    METHODS: UHPLC coupled with high-resolution Orbitrap mass spectrometry (UHPLC/Orbitrap) was set up for the identification and separation ofpolyamines, together with some of their metabolites and catabolites, in the plasma of healthy and prostate cancer human patients. Thirteen metabolites were measured in deproteinized plasma samples through a new analytical approach known as the parallel reaction monitoring (PRM) for targeted quantitative analysis.
    RESULTS: The calibration curves were linear and R2 ranged from 0.9913 to 0.9995 for all analytes. LOQ values are between 0.382 and 25 ng mL-1 and LOD values are between 0.109 and 7.421 ng mL-1. The method shows an accuracy and precision for intra-day and inter-day < 15% RSD and R.E.% for all the QC samples. The matrix effect calculated at different concentration levels did not exceed 15%.
    CONCLUSIONS: The method developed provides rapid, easy and robust identification and measurement of a wide range of polyamines, and some of their metabolites that can be evaluated as biomarkers to predict the clinical features of prostate cancer patients, avoiding invasive diagnostic procedures.
    Keywords:  Biomarkers; Orbitrap mass spectrometer; PRM mode; Plasma polyamines; Prostate cancer; UHPLC
    DOI:  https://doi.org/10.1016/j.jchromb.2020.122468
  9. Molecules. 2020 Dec 18. pii: E6018. [Epub ahead of print]25(24):
      Aging and the emergence of age-associated illnesses are one of the major challenges of our present society. Alzheimer's disease (AD) is closely associated with aging and is defined by increasing memory loss and severe dementia. Currently, there are no therapy options available that halt AD progression. This work investigates three hallmarks of the disease (autophagy, neuroinflammation, and senescence) and systematically analyzes if there is a beneficial effect from three substances derived from food sources, the so called "nutraceuticals" epigallocatechin gallate, fisetin, and spermidine, on these hallmarks. The results imply a positive outlook for the reviewed substances to qualify as a novel treatment option for AD. A combination of nutraceutical substances and other preventive measures could have significant clinical impact in a multi-layered therapy approach to counter AD.
    Keywords:  EGCG; autophagy; cognitive decline; epigenetic; fisetin; neuroinflammation; spermidine
    DOI:  https://doi.org/10.3390/molecules25246018
  10. Crit Rev Food Sci Nutr. 2020 Dec 24. 1-15
      As a ubiquitous and essential part of phytophysiology, phytohormones have attracted tremendous attention for effective regulation of development and senescence of agricultural products. However, the postharvest mechanisms of phytohormones have not been thoroughly understood. This review provides an overview of common phytohormones for extending the shelf life of fruit and vegetables. The modulation principles are discussed in detail based on defence gene expression activation, sensitivity of senescence-related phytohormones inhibition, antioxidant enzymes activity stimulation, and cell membrane integrity maintenance. The applications of jasmonates, salicylic acids, cytokinins, gibberellins, polyamines, and brassinosteroids in preserving fruit and vegetables based on defence signaling network stimulation, senescence-related phytohormones expression or sensitivity repression, as well as antioxidant system enhancement and cell membrane integrity sustentation are introduced. The challenges and problems to be solved are discussed, and new trends of expanding lifespan by combining phytohormones with other treatments are also suggested. Although phytohormones have been demonstrated to have promising efforts in maintaining agricultural products, more novel and effective combination treatments should be developed to complement each other.
    Keywords:  Fruit and vegetables; phytohormones; postharvest storage; preservation
    DOI:  https://doi.org/10.1080/10408398.2020.1864280