bims-polyam Biomed News
on Polyamines
Issue of 2021–11–21
seven papers selected by
Sebastian J. Hofer, University of Graz
  1. Structural basis of binding and inhibition of ornithine decarboxylase by 1-amino-oxy-3-aminopropane.
  2. Exogenous γ-aminobutyric acid maintains fruit quality of apples through regulation of ethylene anabolism and polyamine metabolism.
  3. Hematological, immunological, and polyamines alterations in the concomitant occurrence of Fasciola gigantica and hepatic leiomyoma in cattle.
  4. Putrescine biosynthetic pathways modulate root growth differently in tomato seedlings grown under different N sources.
  5. Nitric oxide and spermidine alleviate arsenic-incited oxidative damage in Cicer arietinum by modulating glyoxalase and antioxidant defense system.
  6. Cryo-EM reveals mechanistic insights into lipid-facilitated polyamine export by human ATP13A2.
  7. Piriformospora indica recruits host-derived putrescine for growth promotion in plants.
  1. Biochem J. 2021 Nov 19. pii: BCJ20210647. [Epub ahead of print]
    Structural basis of binding and inhibition of ornithine decarboxylase by 1-amino-oxy-3-aminopropane.
    X Edward Zhou, Kelly Suino-Powell, Chad R Schultz, Bilal Aleiwi, Joseph S Brunzelle, Jared Lamp, Irving E Vega, Edmund Ellsworth, André S Bachmann, Karsten Melcher.
      Ornithine decarboxylase (ODC) is the rate-limiting enzyme for the synthesis of polyamines (PAs). PAs are oncometabolites that are required for proliferation, and pharmaceutical ODC inhibition is pursued for the treatment of hyperproliferative diseases, including cancer and infectious diseases. The most potent ODC inhibitor is 1-amino-oxy-3-aminopropane (APA). A previous crystal structure of an ODC-APA complex indicated that APA non-covalently binds ODC and its cofactor pyridoxal 5-phosphate (PLP) and functions by competing with the ODC substrate ornithine for binding to the catalytic site. We have revisited the mechanism of APA binding and ODC inhibition through a new crystal structure of APA-bound ODC, which we solved at 2.49 Å resolution. The structure unambiguously shows the presence of a covalent oxime between APA and PLP in the catalytic site, which we confirmed in solution by mass spectrometry. The stable oxime makes extensive interactions with ODC but cannot be catabolized, explaining APA's high potency in ODC inhibition. In addition, we solved an ODC/PLP complex structure with citrate bound at the substrate binding pocket. These two structures provide new structural scaffolds for developing more efficient pharmaceutical ODC inhibitors.
    Keywords:  crystallography; ornithine decarboxylase; polyamines
    DOI:  https://doi.org/10.1042/BCJ20210647
  2. Plant Physiol Biochem. 2021 Nov 10. pii: S0981-9428(21)00566-0. [Epub ahead of print]169 92-101
    Exogenous γ-aminobutyric acid maintains fruit quality of apples through regulation of ethylene anabolism and polyamine metabolism.
    Canying Li, Jie Zhu, Lei Sun, Yuan Cheng, Jiabao Hou, Yiting Fan, Yonghong Ge.
      In this study, 'Golden Delicious' apples were dipped with γ-aminobutyric acid (GABA) solution to investigate the changes of quality parameters, ethylene anabolism, polyamine metabolism and GABA shunt. Results showed that GABA distinctly suppressed respiratory rate, reduced titratable acidity, maintained higher soluble solid content and pericarp firmness of apples. Compared to the control, GABA also repressed the activities and gene expressions of polyamine oxidase (PAO) and diamine oxidase (DAO), enhanced MdMT, MdMS, MdSAMS, MdSAMDC, MdSPDS, MdODC, MdADC, and MdACL5 expressions, and accelerated the accumulation of putrescine, spermidine, and spermine in the exocarp of apples. Moreover, GABA decreased ethylene release, MdACS and MdACO gene expressions in the exocarp. In addition, exogenous GABA activated MdGAD, MdGDH, MdGS expressions and inhibited MdGABA-T and MdSSADH expressions in the GABA shunt, therefore increased endogenous GABA, pyruvic acid and glutamate contents in the exocarp. These findings suggest that exogenous GABA regulates ethylene anabolism, polyamine metabolism and GABA shunt to maintain fruit quality of 'Golden Delicious' apples.
    Keywords:  Ethylene; GABA shunt; Malus domestica; Polyamine; γ-Aminobutyric acid
    DOI:  https://doi.org/10.1016/j.plaphy.2021.11.008
  3. Vet Parasitol. 2021 Nov 05. pii: S0304-4017(21)00277-6. [Epub ahead of print]300 109617
    Hematological, immunological, and polyamines alterations in the concomitant occurrence of Fasciola gigantica and hepatic leiomyoma in cattle.
    Safieh Shahvazi, Saleh Esmaeilzadeh, Somayeh Bahrami, Hossein Najafzadeh.
      No previous studies have investigated the polyamines alterations during fascioliasis due to F. gigantica in ruminants. This study was therefore carried out to find out the possible relationship between the extent of liver destruction and leiomyoma and some hematological and immunological parameters and polyamines alterations in F. gigantica infection. Fifty cattle with liver fascioliasis and fifteen healthy cattle were selected for the study. For the histopathological study, liver tissue samples were stained with hematoxylin and eosin (H&E) and Masson's Trichrome methods. The leiomyoma suspected specimens were immunohistochemically stained for smooth muscle actin and desmin. Different hematological parameters were investigated in infected and non-infected animals. Furthermore, levels of putrescine, spermidine, and spermine were measured in homogenized liver samples. Serum IL-4 and TNF-α levels were also evaluated. By histological examination, the lesions were noted in all the infected specimens. These lesions were varied from leiomyoma, chronic catarrhal cholangitis, arteriosclerosis, telangiectasia, and fresh migratory tunnels filled with RBC and eosinophils. Comparison of hemogram results between infected and non-infected groups revealed a significant decrease in red blood cell counts (RBC), mean corpuscular hemoglobin concentration (MCHC), and platelet count (PLT) in infected animals. Also, a significant elevation in mean corpuscular volume (MCV) concentration was detected in infected animals. The putrescine and spermine levels of the infected animals were significantly higher than the non-infected animals. Although spermidine was increased in infected livers, its elevation was not significant. Based on the results, the level of IL-4 and TNF-α was not significantly changed in infected animals. In conclusion, the concurrent occurrence of leiomyoma and fascioliasis due to F. gigantica and polyamines elevation (putrescine and spermine) is reported for the first time. The role of polyamines in the concurrent occurrence of leiomyoma and fascioliasis is an area for future research.
    Keywords:  Cattle; Fasciola gigantica; Leiomyoma; Liver flukes; Polyamines
    DOI:  https://doi.org/10.1016/j.vetpar.2021.109617
  4. J Plant Physiol. 2021 Nov 14. pii: S0176-1617(21)00199-1. [Epub ahead of print]268 153560
    Putrescine biosynthetic pathways modulate root growth differently in tomato seedlings grown under different N sources.
    Ana Isabel González-Hernández, Loredana Scalschi, Pilar Troncho, Pilar García-Agustín, Gemma Camañes.
      The biosynthesis of putrescine is mainly driven by arginine decarboxylase (ADC) and ornithine decarboxylase (ODC). Hence, in this study, we generated independent ADC and ODC transgenic silenced tomato lines (SilADC and SilODC, respectively) to test the effect of defective ADC and ODC gene expression on root development under nitrate (NN) or ammonium (NA) conditions. The results showed that SilODC seedlings displayed an increase in ADC expression that led to polyamine accumulation, suggesting a compensatory effect of ADC. However, this effect was not observed in SilADC seedlings. These pathways are involved in different growth processes. The SilADC seedlings showed an increase in fresh weight, shoot length, lateral root number and shoot:root ratio under the NN source and an enhancement in fresh weight, and shoot and root length under NA conditions. However, SilODC seedlings displayed greater weight and shoot length under the NN source, whereas a decrease in lateral root density was found under NA conditions. Moreover, two overexpressed ODC lines were generated to check the relevance of the compensatory effect of the ADC pathway when ODC was silenced. These overexpressed lines showed not only an enhancement of almost all the studied growth parameters under both N sources but also an amelioration of ammonium syndrome under NA conditions. Together, these results reflect the importance of both pathways in plant growth, particularly ODC silencing, which requires compensation by ADC induction.
    Keywords:  NH(4)(+) nutrition; Putrescine biosynthetic pathways; Root modulation; Solanum lycopersicum
    DOI:  https://doi.org/10.1016/j.jplph.2021.153560
  5. Funct Plant Biol. 2021 Nov 19.
    Nitric oxide and spermidine alleviate arsenic-incited oxidative damage in Cicer arietinum by modulating glyoxalase and antioxidant defense system.
    Riti Thapar Kapoor, Daniel Ingo Hefft, Ajaz Ahmad.
      Anthropogenic activities such as mining, fossil fuel combustion, fertilisers and pesticides utilisation in agriculture, metallurgic processes and disposal of industrial wastes have contributed an exponential rise in arsenic content in environment. The present paper deals with arsenate (AsV) incited stress in chickpea (Cicer arietinum L.) plants and its alleviation through the application of nitric oxide (NO) and spermidine (SPD). The exposure of C. arietinum to AsV reduced seedling length, biomass, relative water content and biochemical constituents. All the above-mentioned parameters were escalated when sodium nitroprusside (SNP) or SPD were utilised alone or in combination with AsV. The electrolyte leakage and malondialdehyde content were increased in chickpea treated with AsV, but reduced in combine treatment (As+SNP+SPD). In chickpea seedlings, 89.4, 248.4 and 333.3% stimulation were recorded in sugar, proline and glycine betaine contents, respectively, with As+SNP+SPD treatment in comparison to control. SNP and SPD modulated function of glyoxalase enzymes by which methylglyoxal (MG) was significantly detoxified in C. arietinum. Maximum reduction 45.2% was observed in MG content in SNP+SPD treatment over AsV stress. Hence, synergistic application of NO and SPD protected chickpea plants against AsV-generated stress by strengthening the antioxidant defence and glyoxalase system, which helped in regulation of biochemical pathways.
    DOI:  https://doi.org/10.1071/FP21196
  6. Mol Cell. 2021 Nov 15. pii: S1097-2765(21)00949-7. [Epub ahead of print]
    Cryo-EM reveals mechanistic insights into lipid-facilitated polyamine export by human ATP13A2.
    Atsuhiro Tomita, Takashi Daiho, Tsukasa Kusakizako, Keitaro Yamashita, Satoshi Ogasawara, Takeshi Murata, Tomohiro Nishizawa, Osamu Nureki.
      The cytoplasmic polyamine maintains cellular homeostasis by chelating toxic metal cations, regulating transcriptional activity, and protecting DNA. ATP13A2 was identified as a lysosomal polyamine exporter responsible for polyamine release into the cytosol, and its dysfunction is associated with Alzheimer's disease and other neural degradation diseases. ATP13A2 belongs to the P5 subfamily of the P-type ATPase family, but its mechanisms remain unknown. Here, we report the cryoelectron microscopy (cryo-EM) structures of human ATP13A2 under four different conditions, revealing the structural coupling between the polyamine binding and the dephosphorylation. Polyamine is bound at the luminal tunnel and recognized through numerous electrostatic and π-cation interactions, explaining its broad specificity. The unique N-terminal domain is anchored to the lipid membrane to stabilize the E2P conformation, thereby accelerating the E1P-to-E2P transition. These findings reveal the distinct mechanism of P5B ATPases, thereby paving the way for neuroprotective therapy by activating ATP13A2.
    Keywords:  ATP13A2; MD simulation; P-type ATPase; P5B-ATPase; PARK9; Parkinson's disease; cryo-EM; lysosome; membrane protein; polyamine
    DOI:  https://doi.org/10.1016/j.molcel.2021.11.001
  7. Plant Physiol. 2021 Nov 16. pii: kiab536. [Epub ahead of print]
    Piriformospora indica recruits host-derived putrescine for growth promotion in plants.
    Anish Kundu, Shruti Mishra, Pritha Kundu, Abhimanyu Jogawat, Jyothilakshmi Vadassery.
      Growth promotion induced by the endosymbiont Piriformospora indica has been observed in various plants; however, except growth phytohormones, specific functional metabolites involved in P. indica-mediated growth promotion are unknown. Here, we used a GC-MS based untargeted metabolite analysis to identify tomato (Solanum lycopersicum) metabolites whose levels were altered during P. indica-mediated growth promotion. Metabolomic multivariate analysis revealed several primary metabolites with altered levels, with putrescine induced most significantly in roots during the interaction. Further, our results indicated that P. indica modulates the arginine decarboxylase (ADC)-mediated putrescine biosynthesis pathway via induction of SlADC1 in tomato. P. indica did not promote growth in Sladc1-VIGS (virus-induced gene silencing of SlADC1) lines of tomato tomato and showed less colonization. Furthermore, using LC-MS/MS we showed that putrescine promoted growth by elevation of auxin (indole-3-acetic acid) and gibberellin (GA4, GA7) levels in tomato. In Arabidopsis (Arabidopsis thaliana) adc knock-out mutants, P. indica colonization also decreased and showed no plant growth promotion, and this response was rescued upon exogenous application of putrescine. Putrescine is also important for hyphal growth of P. indica, indicating that it is co-adapted by both host and microbe. Taken together, we conclude that putrescine is an essential metabolite and its biosynthesis in plants is crucial for P. indica-mediated plant growth promotion and fungal growth.
    DOI:  https://doi.org/10.1093/plphys/kiab536
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