bims-polyam Biomed News
on Polyamines
Issue of 2020‒02‒09
eight papers selected by
Alexander Ivanov
Engelhardt Institute of Molecular Biology


  1. Inflamm Bowel Dis. 2020 Feb 07. pii: izaa013. [Epub ahead of print]
    Niechcial A, Butter M, Manz S, Obialo N, Bäbler K, van der Lely L, Lang S, Gottier C, McCole DF, Scharl M, Spalinger MR.
      BACKGROUND: The single nucleotide polymorphism (SNP) rs1893217 within the gene locus encoding PTPN2 represents a risk factor for inflammatory bowel disease (IBD). Our previous work demonstrated reduced PTPN2 activity and subsequently increased inflammatory signaling upon presence of SNP rs1893217. The naturally occurring polyamine spermidine reduces pro-inflammatory signaling via induction of PTPN2 activity; however, the effect of SNP rs1893217 on the anti-inflammatory potential of spermidine is still unknown. Here, we investigated how presence of SNP rs1893217 affects treatment efficacy of spermidine and whether it might serve as a potential biomarker for spermidine treatment.METHODS: Human T84 (wild-type [WT] for PTPN2 SNP rs1893217) and HT29 (heterozygous for PTPN2 SNP rs1893217) intestinal epithelial cells (IECs) were treated with several polyamines from the putrescine-spermidine pathway. T84 and HT29 IECs, THP-1 monocytes (WT and transfected with a lentiviral vector expressing PTPN2 SNP rs1893217) and genotyped, patient-derived peripheral blood mononuclear cells were challenged with IFN-γ and/or spermidine.
    RESULTS: Among the analyzed polyamines, spermidine was the most efficient activator of PTPN2 phosphatase activity, regardless of the PTPN2 genotype. Spermidine suppressed IFN-γ-induced STAT1 and STAT3 phosphorylation, along with decreased mRNA expression of ICAM-1, NOD2, and IFNG in IECs and monocytes. Of note, these effects were clearly more pronounced when the disease-associated PTPN2 C-variant in SNP rs1893217 was present.
    CONCLUSIONS: Our data demonstrate that spermidine is the most potent polyamine in the putrescine-spermine axis for inducing PTPN2 enzymatic activity. The anti-inflammatory effect of spermidine is potentiated in the presence of SNP rs1893217, and this SNP might thus be a useful biomarker for possible spermidine-treatment in IBD patients.
    DOI:  https://doi.org/10.1093/ibd/izaa013
  2. Biol Pharm Bull. 2020 ;43(2): 221-229
    Matsumoto M.
      Low molecular weight metabolites produced by the intestinal microbiome that have been associated with health and disease as metabolites need to be constantly absorbed from the intestinal lumen and transported to intestinal epithelial cells and blood. Polyamines, especially spermidine and spermine, are bioactive chemicals which promote autophagy and suppress inflammation. The main source of exogenous polyamines is the intestinal lumen, where they are produced by intestinal microbiome. Considering the intestinal microbiome as a manufacturing plant for bioactive substances, we developed a novel hybrid putrescine biosynthesis system strategy, in which the simultaneous intake of Bifidobacterium animalis ssp. lactis LKM512 (Bifal) and arginine (Arg) upregulates the production of the putrescine, a precursor of spermidine and spermine, in the gut by controlling the bacterial metabolism beyond its vast diversity and inter-individual differences. In a clinical trial, healthy individuals with a body mass index near the maximum "healthy" range (25 kg/m3; n = 44) were randomized to consume either normal yogurt containing Bifal and Arg (Bifal + Arg YG) or placebo (normal yogurt) for 12 weeks. The change in reactive hyperemia index determined by EndoPAT from week 0 to 12 in the Bifal + Arg YG group was significantly higher than that in the placebo group, indicating that Bifal + Arg YG intake improved vascular endothelial function. In addition, the concentrations of fecal putrescine and serum spermidine in the Bifal+ Arg YG group were significantly higher than those in the placebo group. These findings suggest that consuming Bifal + Arg YG prevents or reduces atherosclerosis risk by upregulating blood spermidine levels, which subsequently induces autophagy.
    Keywords:  Bifidobacterium animalis subsp. lactis; arginine; atherosclerosis; intestinal microbiome; metabolomics; polyamine
    DOI:  https://doi.org/10.1248/bpb.b19-00855
  3. Transplantation. 2020 Feb 06.
    Han Z, Li Y, Yang B, Tan R, Wang M, Zhang B, Dai C, Wei L, Chen D, Chen Z.
      BACKGROUND: Liver ischemia reperfusion injury (LIRI) is a common problem during surgical procedures of the liver. It causes severe inflammatory responses and cell death, eventually leading to serious liver damage. Agmatine (AGM) is an endogenous polyamine with analgesic, anti-inflammatory, and antiapoptotic effects. However, it is still unknown whether AGM can protect the liver from damage caused by LIRI.METHODS: For the in vivo experiments, a mouse model of partial warm hepatic ischemia reperfusion was established using C57BL/6 mice and then serum transaminase concentrations were analyzed. Histopathology was used to evaluate the degree of liver injury and quantitative real-time PCR was used to measure the amount of inflammatory cytokines. For in vitro experiments, a cellular model of cobalt chloride (CoCl2)-induced hypoxia was established using AML12 cells. Flow cytometry was performed to measure the apoptosis levels. Western blotting analysis was conducted to measure the levels of proteins involved in apoptosis and Wnt/β-catenin signaling. We also chose 2 inhibitors of the Wnt/β-catenin signaling to elucidate the relationship between AGM and the Wnt/β-catenin signaling.
    RESULTS: AGM showed protective effects against LIRI-induced liver damage, inflammatory responses, and cell apoptosis along with alleviation of CoCl2-induced hepatocyte injury. AGM activated the Wnt/β-catenin signaling pathway during LIRI and CoCl2-induced hepatocyte injury; however, when the Wnt/β-catenin pathway was inhibited, the protective effects of AGM declined.
    CONCLUSIONS: AGM showed protective effects against LIRI by activating the Wnt/β-catenin signaling pathway.
    DOI:  https://doi.org/10.1097/TP.0000000000003161
  4. Plants (Basel). 2020 Feb 01. pii: E179. [Epub ahead of print]9(2):
    Jankovska-Bortkevič E, Gavelienė V, Šveikauskas V, Mockevičiūtė R, Jankauskienė J, Todorova D, Sergiev I, Jurkonienė S.
      Cold stress is one of the most common abiotic stresses experienced by plants and is caused by low temperature extremes and variations. Polyamines (PAs) have been reported to contribute in abiotic stress defense processes in plants. The present study investigates the survival and responses of PA-treated non-acclimated (N) and acclimated (A) winter oilseed rape to increasing cold conditions. The study was conducted under controlled conditions. Seedlings were foliarly sprayed with spermidine (Spd), spermine (Spm), and putrescine (Put) solutions (1 mM) and exposed to four days of cold acclimation (4 °C) and two days of increasing cold (from -1 to -3 °C). Two cultivars with different cold tolerance were used in this study. The recorded traits included the percentage of survival, H+-ATPase activity, proline accumulation, and ethylene emission. Exogenous PA application improved cold resistance, maintained the activity of plasma membrane H+-ATPase, increased content of free proline, and delayed stimulation of ethylene emission under increasing cold. The results of the current study on winter oilseed rape revealed that foliar application of PAs may activate a defensive response (act as elicitor to trigger physiological processes), which may compensate the negative impact of cold stress. Thus, cold tolerance of winter oilseed rape can be enhanced by PA treatment.
    Keywords:  Brassica napus; acclimation; canola; cold stress; cold tolerance; crop plants; putrescine; spermidine; spermine
    DOI:  https://doi.org/10.3390/plants9020179
  5. Plant Cell Environ. 2020 Feb 04.
    Cui J, Pottosin I, Lamade E, Tcherkez G.
      Biomarker metabolites are of increasing interest in crops since they open avenues for precision agriculture, whereby nutritional needs and stresses can be monitored optimally. Putrescine has the potential to be a useful biomarker to reveal potassium (K+ ) deficiency. In fact, although this diamine has also been observed to increase during other stresses such as drought, cold or heavy metals, respective changes are comparably low. Due to its multifaceted biochemical properties, several roles for putrescine under K+ deficiency have been suggested, such as cation balance, antioxidant, reactive oxygen species (ROS) mediated signaling, osmolyte, or pH regulator. However, the specific association of putrescine build-up with low K+ availability in plants remains poorly understood, and possible regulatory roles must be consistent with putrescine concentration found in plant tissues. We hypothesize that massive increase of putrescine upon K+ starvation plays an adaptive role. A distinction of putrescine function from that of other polyamines (spermine, spermidine) may be based either on its specificity or (which is probably more relevant under K+ deficiency) on a very high attainable concentration of putrescine, which far exceeds those for spermidine and spermine. Excessive putrescine and its catabolites appear to possess a strong potential in controlling cellular K+ and Ca2+ , and mitochondria and chloroplasts bioenergetics under K+ stress. This article is protected by copyright. All rights reserved.
    Keywords:  deficiency; ion balance; polyamines; potassium; putrescine
    DOI:  https://doi.org/10.1111/pce.13740
  6. Antimicrob Agents Chemother. 2020 Feb 03. pii: AAC.02040-19. [Epub ahead of print]
    Ben Jeddou F, Falconnet L, Luscher A, Siriwardena T, Reymond JL, van Delden C, Köhler T.
      Colistin (polymyxin E) is a last resort antibiotic against multidrug-resistant isolates of Pseudomonas aeruginosa However, the nephro-toxicity of colistin limits its use, spurring the interest in novel antimicrobial peptides (AMP). Here we show that the synthetic dendrimer AMPs G3KL (MW 4531.38, 15 positive charges, MIC = 8 mg/L) showed faster killing than polymyxin B (Pmx-B) and no detectable resistance selection in P. aeruginosa strain PA14. Spontaneous mutants selected on Pmx-B, harboring loss of function mutations in the PhoQ sensor kinase gene, showed increased Pmx-B MICs and arnB operon expression (4-amino-L-arabinose addition to lipid A), but remained susceptible to dendrimers. Two mutants carrying a missense mutation in the periplasmic loop of the PmrB sensor kinase showed increased MICs for Pmx-B (8-fold) and G3KL (4-fold) but not for the dendrimer T7 (MW 4885.64, 16 positive charges, MIC = 8 mg/L). The pmrB mutants showed increased expression of the arnB as well as of the speD2-speE2-PA4775 operon, located upstream of pmrAB, and involved in polyamine biosynthesis. Exogenous supplementation with the polyamines spermine and norspermine increased G3KL and T7 MICs in a phoQ mutant background but not in the PA14 wild-type. This suggests that both addition of 4-amino-L-arabinose and secretion of polyamines are required to reduce susceptibility to dendrimers, probably neutralizing the negative charges present on the lipid A and the KDO sugars of the LPS, respectively. We further show by transcriptome analysis that the dendrimers G3KL and T7 induce adaptive responses through the CprRS two-component system in PA14.
    DOI:  https://doi.org/10.1128/AAC.02040-19
  7. J Agric Food Chem. 2020 Feb 04.
    Zou D, Min Y, Liu Y, Wei X, Wang J.
      Spermidine possesses multiple healthy functions, and soybeans contain the most abundant spermidine. In this study, spermidine contents of soybeans from different varieties and production regions in China were evaluated, and a spermidine synthase gene (speE) was identified by recombinant expression, transcriptional verification and sequence analysis. Spermidine contents of soybean samples from 18 varieties ranged 72.38-228.82 mg/Kg, and those from 19 production regions ranged 134.64-242.32 mg/Kg. The highest-spermidine sample GZ was used to clone four predicted speE genes. Expressing the gene speE5 improved the spermidine titer by 54% in Bacillus amyloliquefaciens, confirming that speE5 was involved in spermidine synthesis. Transcriptional verification was performed through a soybean germination model. Germination for 48 h led to a 1-fold increase of spermidine in samples SHX and HB, and corresponding speE5 transcriptional levels were improved by 26-fold and 18-fold, respectively, further verifying the function of speE5. Finally, the sequences of speE5 gene and deduced amino acids were analyzed, and the conserved sites and catalysis mechanism were presented. This study identified an active spermidine synthase gene from soybean for the first time, which provided an important gene resource for genetic breeding of spermidine-rich soybean or microbial cell factory.
    DOI:  https://doi.org/10.1021/acs.jafc.9b07443
  8. Anal Biochem. 2020 Jan 29. pii: S0003-2697(19)30262-3. [Epub ahead of print] 113607
    Sugiyama Y, Ohta H, Hirano R, Shimokawa H, Sakanaka M, Koyanagi T, Kurihara S.
      Quantification of polyamines, including putrescine, is generally performed using high-performance liquid chromatography (HPLC) or gas chromatography. However, these methods are time-consuming because of sample derivatization and analytical reagent preparation. In this study, we developed a simple and high-throughput putrescine quantification method on a 96-well microtiter plate using putrescine oxidase from Rhodococcus erythropolis NCIMB 11540, peroxidase, 4-aminoantipyrine, and N-ethyl-N-(3-sulfopropyl)-3-methylaniline sodium salt. The developed method (named as PuO-POD-4AA-TOPS method) was applicable to bacterial culture supernatants. Furthermore, putrescine concentrations determined by the developed method roughly corresponded to the concentrations determined by HPLC.
    DOI:  https://doi.org/10.1016/j.ab.2020.113607