bims-polyam Biomed News
on Polyamines
Issue of 2021‒12‒05
six papers selected by
Sebastian J. Hofer
University of Graz


  1. Mol Nutr Food Res. 2021 Nov 30. e2100639
      SCOPE: The impacts of longevity-promoting probiotic Bifidobacterium animalis subsp. lactis LKM512 (LKM512) on metabolic disease remain unclear. Here we aimed to explore the potential of LKM512 on the host physiological function and gut microbiota in high-fat diet-induced obese mice.METHODS AND RESULTS: LKM512 were orally administrated for 12 weeks, and the effects of LKM 512 on systemic inflammation and insulin resistance, as well as gut microbiota, were investigated in high-fat (HF) diet-induced obese mice. LKM512 supplementation ameliorated hepatic lipid accumulation, attenuated hepatic and adipose tissue inflammation, and improved intestinal barrier function. These results were associated with improved insulin sensitivity and metabolic endotoxemia. Furthermore, the colonization of LKM512 induced an increase in polyamine metabolism and production, together with significant alternations in the composition and function of gut microbiota in obese mice, which were correlated with these improved metabolic phenotypes in the host.
    CONCLUSION: The probiotic strain LKM512 might become a promising strategy to improve obesity and related metabolic disorders. This article is protected by copyright. All rights reserved.
    Keywords:  Obesity; gut barrier; gut microbiota; inflammation; probiotics
    DOI:  https://doi.org/10.1002/mnfr.202100639
  2. Genomics. 2021 Nov 26. pii: S0888-7543(21)00410-9. [Epub ahead of print]
      Bladder cancer has a high incidence worldwide accompanies by high recurrent rate after treatment. The emergence of primary or acquired chemotherapy resistance leads to poor efficacy in many cases. To explore the underlying mechanisms of drug resistance, we firstly established a drug-resistant cell model T24/THP by repeated exposure of T24 cells to pirarubicin (THP) whose concentration increases gradually. Non-targeted metabolomics was performed to identify metabolic changes and key metabolism pathways variance in T24/THP cells. Pathway enrichment analysis demonstrated that the arginine and proline metabolic pathway was the most significantly changed pathway, where two representative members of polyamine, putrescine and spermidine were remarkably down regulated in T24/THP. Subsequent experiments further confirmed that ornithine decarboxylase (ODC1) and spermidine synthase (SRM), the key enzymes involved in the synthesis of these compounds, also showed a stable low expression in T24/THP. However, knocking down of ODC1 and SRM sensitized cells to chemotherapy treatment while overexpression of these two enzymes enhances chemotherapy resistance. This leaded to the point that ODC1 and SRM themselves are more likely to promote the drug resistance, which appears to contradict their low expression in T24/THP. We hypothesize that their diminished levels were due to the declined activity of genes upstream. According to this line of thought, we found that c-MYC was also down-regulated in T24/THP and its content could be significantly affected by drug administration. In addition, c-MYC could not only regulate the expression levels of ODC1 and SRM but also influence drug resistance in T24/THP. In conclusion, alterations in gene expression of ODC1 and SRM in drug resistance cell line is probably mediated by some upstream regulators rather than antineoplastic agents alone. Exploration of upstream signals and research on detailed regulatory mechanism, thereby understanding the actual role of c-MYC and polyamine in response to chemotherapy, can become a potential field direction to overcome drug resistance in bladder cancer.
    Keywords:  Bladder cancer; Metabonomics; Multi-drug resistance; Polyamine metabolism
    DOI:  https://doi.org/10.1016/j.ygeno.2021.11.028
  3. Plant Physiol Biochem. 2021 Nov 28. pii: S0981-9428(21)00604-5. [Epub ahead of print]170 64-74
      Polyamine (PA), one of the important plant growth regulators, is closely associated with drought stress. However, the function of conjugated PA is not still clear in the roots of cucumber seedlings under polyethylene glycol (PEG) osmotic stress. Therefore, in this study the relationship between the levels of conjugated polyamines and the activity of H+-ATPase in plasma membrane was elucidated with the roots of two cucumber (Cucumis sativus L.) cultivars, which were different in drought tolerance, as experimental materials. Furthermore, the contents of free PAs and the activities of S-adenosylmethionine decarboxylase (SAMDC) and transglutaminase (TGase), which were closely related to the levels of conjugated polyamines, were also determined. Results showed that under osmotic stress, the increases of the levels of non-covalently conjugated (non-CC) spermidine (Spd) and spermine (Spm), covalently conjugated (CC) putrescine (Put) and Spd in plasma membrane of drought-tolerant Tangshan 5 were more obvious than those of drought-sensitive Jinyou 1. Furthermore, the conjugated PAs mentioned above were closely correlated with increase rate of seedling dry weight, plasma membrane permeability, water content and H+-ATPase activity in plasma membrane. Results of the additional tests, in which exogenous Spd, Spm and two inhibitors, MGBG and phenanthrolin were used, were complementary to the results above. From these results, it could be concluded that non-CC Spd and Spm, CC Put and Spd in plasma membrane functioned in enhancing the tolerance of cucumber seedlings to osmotic stress via elevating H+-ATPase activity.
    Keywords:  Conjugated polyamines; Cucumber (Cucumis sativus L.); H(+)-ATPase; Osmotic stress
    DOI:  https://doi.org/10.1016/j.plaphy.2021.11.040
  4. Genomics. 2021 Nov 25. pii: S0888-7543(21)00411-0. [Epub ahead of print]
      Plant ODC (ornithine decarboxylase) plays a vital role in normalizing cell division in actively growing tissues. The ODC is a key precursor enzyme for nicotine and nornicotine biosynthesis in plants. ODCs are widely present in many plant families but have not been functionally validated and characterized at the molecular level. In the present study, 58 plant ODCs were identified and were found to contain two putative regulatory motifs, specifically PLP (Pyridoxal 5'-phosphate) and Orn/DAP/Arg decarboxylase family 2 pyridoxal-phosphate, that are highly conserved among diverse plant species. Further, the cis-regulatory elements and interacting partners of the gene revealed the importance of ODC in various metabolic pathways. The qRT-PCR revealed highest relative expression of ODC in floral meristem and roots. Our results suggest that ODC can be effectively used as an ideal candidate for engineering polyamine biosynthesis and would be crucial for developing ultra-low nicotine content tobacco lines via genome editing.
    Keywords:  Motifs; Nicotiana tabacum; Ornithine decarboxylase; Polyamines
    DOI:  https://doi.org/10.1016/j.ygeno.2021.11.029
  5. Plant J. 2021 Nov 30.
      The kinetochore is a supramolecular protein complex assembled on the chromosomes, essential for faithful segregation of the genome during cell divisions. More than 100 proteins are known to constitute the eukaryotic kinetochore architecture, primarily identified using non-plant organisms. A majority of them are fast evolving and are under positive selection. Thus, functional characterization of the plant kinetochore proteins is limited as only a few conserved orthologs sharing sequence similarities with their animal counterparts have been examined. Here, we report the functional characterization of the Arabidopsis thaliana homolog of the yeast NNF1/human PMF1 outer kinetochore protein and show that it has both kinetochore and non-kinetochore functions in plant growth and development. Knockout of NNF1 causes embryo lethality implying its essential role in cell division. AtNNF1 interacts with MIS12 in a Y2H and co-immuno pull down assay, confirming it as one of the constituents of the plant MIS12 complex. GFP-NNF1 localizes to the kinetochore, rescuing the embryo lethal nnf1-1-/- phenotype, but the rescued plants (GFP-NNF1nnf1-/- ) are dwarf displaying hypomorphic phenotypes with no evidence of mitotic or meiotic segregation defects. GFP-NNF1nnf1-/- dwarf plants have reduced levels of endogenous polyamines, which are partially rescued to WT upon exogenous application of polyamines. Mutations in the putative leucine zipper binding motif of NNF1 gave rise to a dominant-negative tall plant phenotype reminiscent of constitutive gibberellin action. These contrasting hypomorphic dwarf and anti morphic tall phenotypes facilitated us to attribute a moonlighting role for Arabidopsis NNF1 affecting polyamine and gibberellin metabolism other than its primary role in kinetochores.
    Keywords:  Arabidopsis; MIS12 complex; NNF1; centromeres; gibberellic acid; kinetochore; mitosis; moonlighting; polyamines
    DOI:  https://doi.org/10.1111/tpj.15614
  6. Plant Physiol Biochem. 2021 Nov 26. pii: S0981-9428(21)00586-6. [Epub ahead of print]170 87-97
      The stomatal aperture is imperative for photosynthesis in higher plants. The function of polyamines (PAs) in stomatal regulation under a stressful environment has not been fully determined. In this study, we demonstrated the mechanism by which putrescine (Put) regulates stomatal changes in cucumber leaves under salt stress. The results showed that foliar application of Put alleviated the decrease of stomatal aperture and photosynthesis caused by salt stress and promoted plant growth. Exogenous Put caused a significant increase in endogenous PAs and hydrogen peroxide (H2O2) levels by 105.43% and 27.97%, respectively, while decreased abscisic acid (ABA) content by 67.68% under salt stress. However, application of inhibitors of aminoguanidine hydrochloride (AG), 1, 8-diaminooctane (1, 8-DO), diphenyleneiodonium chloride (DPI) and salicylhydroxamic acid (SHAM) upregulated the 9-cis-cyclocarotenoid dioxygenase (NCED) gene and downregulated the reduced glutathione synthetase (GSHS) gene. These inhibitors also decreased the stomatal aperture, levels of H2O2 and reduced glutathione (GSH), but increased the ABA content under salt stress and Put treatment conditions. The order of influence is AG > 1, 8-DO > DPI > SHAM. However, Put-induced downregulation of ABA content and upregulation of GSH content under salt stress were effectively blocked by N, N'-dimethylthiourea (DMTU, H2O2 scavenger) and 1-chloro-2,4-dinitrobenzene (CDNB, GSH scavenger) treatments. Taken together, these results suggest that Put induced the formation of H2O2 signaling mediates the degradation of PAs by diamine oxidase (DAO), increasing GSH content and inhibiting the accumulation of ABA in leaves, thereby promoting stomatal opening in salt-stressed cucumber leaves.
    Keywords:  Abscisic acid; Cucumber; Glutathione; Hydrogen peroxide; Putrescine; Salt stress; Stomata
    DOI:  https://doi.org/10.1016/j.plaphy.2021.11.028