bims-polyam Biomed News
on Polyamines
Issue of 2021–05–30
eight papers selected by
Sebastian J. Hofer, University of Graz



  1. J Cell Sci. 2021 May 26. pii: jcs.253781. [Epub ahead of print]
      In Saccharomyces cerevisiae, the selective autophagic degradation of mitochondria, termed mitophagy, is critically regulated by the adapter protein, Atg32. Despite our knowledge about the molecular mechanisms by which Atg32 controls mitophagy, its physiological roles in yeast survival and fitness remains less clear. Here, we demonstrate a requirement for Atg32 in promoting spermidine production during respiratory growth and heat-induced mitochondrial stress. During respiratory growth, mitophagy-deficient yeast exhibit profound heat-stress induced defects in growth and viability due to impaired biosynthesis of spermidine and its biosynthetic precursor S-Adenosyl-Methionine (SAM). Moreover, spermidine production is crucial for the induction of cytoprotective nitric oxide (NO) during heat stress. Hence, the re-addition of spermidine to Atg32 mutant yeast is sufficient to both enhance NO production and restore respiratory growth during heat stress. Our findings uncover a previously unrecognized physiological role for yeast mitophagy in spermidine metabolism and illuminate new interconnections between mitophagy, polyamine biosynthesis and NO signaling.
    Keywords:  ATG32; Autophagy; Mitophagy; Nitric Oxide; S-Adenosyl-Methionine; Spermidine
    DOI:  https://doi.org/10.1242/jcs.253781
  2. Plant Sci. 2021 Jul;pii: S0168-9452(21)00116-3. [Epub ahead of print]308 110923
      Polyamines play a fundamental role in the functioning of all cells. Their regulatory role in plant development, their function under stress conditions, and their metabolism have been well documented as regards both synthesis and catabolism in an increasing number of plant species. However, the majority of these studies concentrate on the levels of the most abundant polyamines, sometimes providing data on the enzyme activity or gene expression levels during polyamine synthesis, but generally making no mention of the fact that changes in the polyamine pool are very dynamic, and that other processes are also involved in the regulation of actual polyamine levels. Differences in the distribution of individual polyamines and their conjugation with other compounds were described some time ago, but these have been given little attention. In addition, the role of polyamine transporters in plants is only now being recognised. The present review highlights the importance of conjugated polyamines and also points out that investigations should not only deal with the polyamine metabolism itself, but should also cover other important questions, such as the relationship between light perception and the polyamine metabolism, or the involvement of polyamines in the circadian rhythm.
    Keywords:  Circadian rhythm; Conjugation; Light; Polyamine; Transport
    DOI:  https://doi.org/10.1016/j.plantsci.2021.110923
  3. Microb Physiol. 2021 May 27. 1-15
      Soil bacteria from the genus Streptomyces, phylum Actinobacteria, feature a complex metabolism and diverse adaptations to environmental stress. These characteristics are consequences of variable nutrition availability in the soil and allow survival under changing nitrogen conditions. Streptomyces coelicolor is a model organism for Actinobacteria and is able to use nitrogen from a variety of sources including unusual compounds originating from the decomposition of dead plant and animal material, such as polyamines or monoamines (like ethanolamine). Assimilation of nitrogen from these sources in S. coelicolor remains largely unstudied. Using microbiological, biochemical and in silico approaches, it was recently possible to postulate polyamine and monoamine (ethanolamine) utilization pathways in S. coelicolor. Glutamine synthetase-like enzymes (GS-like) play a central role in these pathways. Extensive studies have revealed that these enzymes are able to detoxify polyamines or monoamines and allow the survival of S. coelicolor in soil containing an excess of these compounds. On the other hand, at low concentrations, polyamines and monoamines can be utilized as nitrogen and carbon sources. It has been demonstrated that the first step in poly-/monoamine assimilation is catalyzed by GlnA3 (a γ-glutamylpolyamine synthetase) and GlnA4 (a γ-glutamylethanolamide synthetase), respectively. First insights into the regulation of polyamine and ethanolamine metabolism have revealed that the expression of the glnA3 and the glnA4 gene are controlled on the transcriptional level.
    Keywords:  Ethanolamine metabolism; GS-like enzyme; GlnA; GlnA2; GlnA3; GlnA4; Nitrogen assimilation; Polyamine metabolism; S. coelicolor
    DOI:  https://doi.org/10.1159/000516644
  4. APMIS. 2021 May 28.
       AIM: The key regulator of the polyamine biosynthetic pathway is ornithine decarboxylase (ODC). ODC is activated by antizyme inhibitor 1 (AZIN1) and 2 (AZIN2). AZIN1 and recently AZIN2 have been related to cancer, however, their functions in adenoid cystic carcinoma (ACC) have not been studied. We evaluated the immunoexpression of AZIN1 and 2 in tumor tissue from ACC patients, and related the results to clinical and clinicopathological features and patient survival.
    STUDY DESIGN: We performed immunohistochemical study on minor salivary and mucous gland ACC tissue samples of patients treated at the Helsinki University Hospital (Helsinki, Finland) during 1974-2012. We scored AZIN1 and 2 immunoexpression in 42 and 45 tumor tissue samples, respectively, and correlated them with clinicopathological factors and survival.
    RESULTS: Enhanced AZIN2 expression was associated with better survival. In addition, both AZINs were seen more commonly in cribriform and tubular than in solid growth patterns. AZIN1 expression did not correlate with the studied clinicopathological factors.
    CONCLUSIONS: It seems that AZIN2 expression is higher in cancer tissue with secretory functions. In ACC tissue, high AZIN2 expression could be related to well-differentiated histological type which still has a functioning vesicle transportation system. Thus, AZIN2 could be a prognostic factor for better survival of ACC patients.
    Keywords:  adenoid cystic carcinoma; antizyme inhibitor; ornithine decarboxylase; prognosis
    DOI:  https://doi.org/10.1111/apm.13158
  5. Plant Physiol Biochem. 2021 May 19. pii: S0981-9428(21)00265-5. [Epub ahead of print]165 147-160
      S-adenosylmethionine decarboxylase (SAMDC) mediates the biosynthesis of polyamines (PAs) and plays a positive role in plants' response to adversity stress tolerance. In this study, we isolated a SAMDC gene from white clover, which is located in mitochondria. It was strongly induced when white clover exposed to drought (15% PEG6000), salinity (200 mM NaCl), 20 μM spermidine, 100 μM abscisic acid, and 10 mM H2O2, especially in leaves. The INVSc1 yeast introduced with TrSAMDC1 had tolerance to drought, salt, and oxidative stress. Overexpression of TrSAMDC1 in Arabidopsis showed higher fresh weight and dry weight under drought and salt treatment and without growth inhibition under normal conditions. Leaf senescence induced by drought and saline was further delayed in transgenic plants, regardless of cultivation in 1/2 MS medium and soil. During drought and salt stress, transgenic plants exhibited a significant increase in relative water content, maximum photosynthesis efficiency (Fv/Fm), performance index on the absorption basis (PIABS), activities of antioxidant protective enzymes such as SOD, POD, CAT, and APX, and a significant decrease in accumulation of MDA and H2O2 as compared to the WT. The concentrations of total PAs, putrescine, spermidine, and spermidine in transgenic lines were higher in transgenic plants than in WT under normal and drought conditions. These results suggested that TrSAMDC1 could effectively mitigate abiotic stresses without the expense of production and be a potential candidate gene for improving the drought and salt resistance of crops.
    Keywords:  Drought stress; Polyamines; ROS detoxification; Salt stress; TrSAMDC1; White clover
    DOI:  https://doi.org/10.1016/j.plaphy.2021.05.018
  6. Saudi J Biol Sci. 2021 May;28(5): 2619-2625
      This study investigated the stress responses of cinnamic acid (CA) in pea plants and explored the protective role of spermidine (SPD) against CA-induced adverse effects. Pea seedlings exposed to CA had reduced length, biomass, moisture, chlorophyll, sugar, and protein contents and reduced nitrate reductase activity. These parameters increased when SPD was applied alone and in combination with CA. Electrolyte leakage and malondialdehyde content were high in seedlings treated with CA but decreased when the SPD + CA treatment was applied. Foliar exposure to SPD partially mitigated CA-induced stress effects by strengthening the antioxidant defense system, which helped preserve the integrity of biochemical processes. These results indicate that SPD (1 mM) could mitigate the adverse effects of CA and enhance plant defense system. Hence, SPD can be used as a growth regulator for the maintenance of physiological functions in pea plants in response to the pernicious consequences of CA stress.
    Keywords:  Antioxidants; BSA, Bovine serum albumin; CA, cinnamic acid; CAT, catalase; Cinnamic acid; EC, electrolyte leakage; EDTA, ethylene diamine tetra acetic acid; GPX, guaiacol peroxidase; Growth; IAA, indole-3-acetic acid; N-1-NEDD, n-1-naphthyl-ethylene diamine dihydrochloride; NBT, nitro blue tetrazolium; NR, nitrate reductase; PA, polyamine; Pisum sativum; ROS, reactive oxygen species; RWS, relative water content; SOD, superoxide dismutase; SPD, spermidine; Spermidine
    DOI:  https://doi.org/10.1016/j.sjbs.2021.02.052
  7. Phytochemistry. 2021 May 19. pii: S0031-9422(21)00143-6. [Epub ahead of print]188 112794
      Polyamines and polyamides have a fundamental role in the biology of plants, and the presence of NO seems compulsory to account for their actions. In general, the NO production has claimed to occur through an enzymatic process, but not involving polyamines and polyamides. Nevertheless, a non-enzymatic mechanism, such as an electron transfer process among polyamines or polyamides and an acid nitrite solution, could account for rapid production of NO, even in anoxic conditions. EPR experiments, carried out with these substrates, proved the formation of NO. This evidence supports a non-enzymatic mechanism as an alternative source of NO, even in plants. So, since the NO production seems directly dependent on polyamines or polyamides presence, and these responsible for many activities in plants, it comes plausibly to consider crucial the involvement of NO in their actions. Furthermore, as for mammals, these results would confirm that, even in plants, NO production can occur through both enzymatic and non-enzymatic mechanisms.
    Keywords:  Antimicrobial; Antioxidant; EPR spectroscopy; Nitric oxide; Polyamide; Polyamine
    DOI:  https://doi.org/10.1016/j.phytochem.2021.112794
  8. Virol Sin. 2021 May 26.
      The emergence and re-emergence of RNA virus outbreaks highlight the urgent need for the development of broad-spectrum antivirals. Polyamines are positively-charged small molecules required for the infectivity of a wide range of RNA viruses, therefore may become good antiviral targets. Cucurbit[7]uril (CB[7]), a synthetic macrocyclic molecule, which can bind with amine-based organic compounds with high affinity, has been shown to regulate bioactive molecules through competitive binding. In this study, we tested the antiviral activity of CB[7] against diverse RNA viruses, including a panel of enteroviruses (i.e. human enterovirus A71, coxsackievirus A16, coxsackievirus B3, and echovirus 11), some flaviviruses (i.e. dengue virus and Zika virus), and an alphavirus representative Semliki forest virus. CB[7] can inhibit virus replications in a variety of cell lines, and its mechanism of action is through the competitive binding with polyamines. Our findings not only for the first time provide evidence that CB[7] can be a promising broad-spectrum antiviral agent, but more importantly, offer a novel therapeutic strategy to fight against RNA viruses by supramolecular sequestration of polyamines.
    Keywords:  Broad-spectrum antiviral activity; Cucurbit[7] (CB[7]); RNA viruses
    DOI:  https://doi.org/10.1007/s12250-021-00404-9