bims-polyam 2023-01-22 papers

bims-polyam

Biomed News

on Polyamines

Issue of 2023–01–22
eight papers selected by
Sebastian J. Hofer, University of Graz

Antizyme Inhibitor 2-Deficient Mice Exhibit Altered Brain Polyamine Levels and Reduced Locomotor Activity.
Isolation of the high polyamine-producing bacterium Staphylococcus epidermidis FB146 from fermented foods and identification of polyamine-related genes.
Structural change study of pepsin in the presence of spermidine trihydrochloride: Insights from spectroscopic to molecular dynamics methods.
Polyamine metabolizing rhizobacteria Pseudomonas sp. GBPI_506 modulates hormone signaling to enhance lateral roots and nicotine biosynthesis in Nicotiana benthamiana.
Cinnamon (Cinnamomum cassia) water extract improves diarrhea symptoms by changing the gut environment: a randomized controlled trial.
Interconnected Set of Enzymes Provide Lysine Biosynthetic Intermediates and Ornithine Derivatives as Key Precursors for the Biosynthesis of Bioactive Secondary Metabolites.
Metabolic landscape dysregulation in bronchoalveolar lavage fluid of checkpoint inhibitor pneumonitis.
Pathogenesis of bronchopulmonary dysplasia in preterm neonates revealed by an RNA sequencing interaction network analysis.

Biomolecules. 2022 Dec 21. pii: 14. [Epub ahead of print]13(1):

Antizyme Inhibitor 2-Deficient Mice Exhibit Altered Brain Polyamine Levels and Reduced Locomotor Activity.

Ana Lambertos, Maria Angeles Nuñez-Sanchez, Carlos López-García, Andrés Joaquín López-Contreras, Bruno Ramos-Molina, Rafael Peñafiel.

   BACKGROUND: Alterations in the neural polyamine system are known to be associated with different brain pathological conditions. In addition, the regulation of enzymes involved in polyamine metabolism such as ornithine decarboxylase (ODC), antizymes (AZs), and antizyme inhibitors (AZINs) is critical during brain development. However, while most studies focus on ODC and AZs, less is known about AZIN expression and function in the brain. Thus, our aim was to analyze the expression pattern of AZIN2 during postnatal development, its brain distribution, and its possible implication in phenotypical alterations.
METHODS: The expression pattern of Azin2 and other genes related to polyamine metabolism was analyzed by RT-qPCR. β-D-galactosidase staining was used to determine the anatomical distribution of AZIN2 in a Azin2 knockout model containing the βGeo marker. Brain polyamine content was determined by HPLC. The Rota-Rod and Pole functional tests were used to evaluate motor skills in Azin2-lacking mice.
RESULTS: Our results showed that expression of genes codifying for AZs and AZINs showed a similar increasing pattern over time that coincided with a decrease in ODC activity and putrescine levels. The analysis of AZIN2 distribution demonstrated that it is strongly expressed in the cerebellum and distributed along the neuron body and dendrites. The ablation of Azin2 showed a decrease in putrescine levels and is related to reduced motor skills.
CONCLUSIONS: Our study revealed that AZIN2 expression in the brain is particularly limited to the cerebellum. In addition, the ablation of Azin2 leads to a reduction in putrescine that relates to alterations in motor function, suggesting the role of AZIN2 in the functioning of dopaminergic neurons.

Keywords:  AZIN2; gene expression; motoneurons; mouse brain; polyamines

DOI:  https://doi.org/10.3390/biom13010014
Biosci Microbiota Food Health. 2023 ;42(1): 24-33

Isolation of the high polyamine-producing bacterium Staphylococcus epidermidis FB146 from fermented foods and identification of polyamine-related genes.

Hideto Shirasawa, Chisato Nishiyama, Rika Hirano, Takashi Koyanagi, Shujiro Okuda, Hiroki Takagi, Shin Kurihara.

  It has been reported that the intake of polyamines contributes to the extension of healthy life span in animals. Fermented foods contain high concentrations of polyamines thought to be derived from fermentation bacteria. This suggests that bacteria that produce high levels of polyamines could be isolated from fermented foods and utilized as a source of polyamines for human nutrition. In this study, Staphylococcus epidermidis FB146 was isolated from miso, a Japanese fermented bean paste, and found to have a high concentration of putrescine in its culture supernatant (452 μM). We analyzed the presence of polyamines in the culture supernatants and cells of the type strains of 21 representative Staphylococcus species in addition to S. epidermidis FB146, and only S. epidermidis FB146 showed high putrescine productivity. Furthermore, whole-genome sequencing of S. epidermidis FB146 was performed, and the ornithine decarboxylase gene (odc), which is involved in putrescine synthesis, and the putrescine:ornithine antiporter gene (potE), which is thought to contribute to the release of putrescine into the culture supernatant, were present on plasmid DNA harbored by S. epidermidis FB146.

Keywords:  Staphylococcus epidermidis; fermented foods; miso; polyamine

DOI:  https://doi.org/10.12938/bmfh.2022-011
Spectrochim Acta A Mol Biomol Spectrosc. 2023 Jan 04. pii: S1386-1425(22)01412-3. [Epub ahead of print]291 122264

Structural change study of pepsin in the presence of spermidine trihydrochloride: Insights from spectroscopic to molecular dynamics methods.

Atefeh Habibi, Sadegh Farhadian, Behzad Shareghi, Fatemeh Hashemi-Shahraki.

  Spermidine is an aliphatic polyamine that directs a set of biological processes. This work aimed to use UV-Vis spectroscopy, fluorescence spectroscopy, thermal stability, kinetic methods, docking, and molecular dynamic simulations to examine the influence of spermidine trihydrochloride (SP) on the structure and function of pepsin. The results of the fluorescence emission spectra indicated that spermidine could quench pepsin's intrinsic emission in a static quenching process, resulting in the formation of the pepsin-spermidine complex. The results discovered that spermidine had a strong affinity to the pepsin structure because of its high binding constant. The obtained results from spectroscopy and molecular dynamic approaches showed the binding interaction between spermidine and pepsin, induced micro-environmental modifications around tryptophan residues that caused a change in the tertiary and secondary structure of the enzyme. FTIR analysis showed hypochromic effects in the spectra of amide I and II and redistribution of the helical structure. Moreover, the molecular dynamic (MD) and docking studies confirmed the experimental data. Both experimental and molecular dynamics simulation results clarified that electrostatic bond interactions were dominant forces.

Keywords:  And simulations method; Molecular docking; Pepsin; Spectroscopic techniques; Spermidine trihydrochloride

DOI:  https://doi.org/10.1016/j.saa.2022.122264
Plant Physiol Biochem. 2023 Jan 09. pii: S0981-9428(23)00014-1. [Epub ahead of print]195 193-205

Polyamine metabolizing rhizobacteria Pseudomonas sp. GBPI_506 modulates hormone signaling to enhance lateral roots and nicotine biosynthesis in Nicotiana benthamiana.

Rahul Jain, Priyanka Bhardwaj, Shweta Guleria, Anita Pandey, Sanjay Kumar.

  Beneficial rhizobacteria in the soil are important drivers of plant health and growth. In this study, we provide the draft genome of a root colonizing and auxin-producing Pseudomonas sp. strain GBPI_506. The bacterium was investigated for its contribution in the growth of Nicotiana benthamiana (Nb) and biosynthesis of nicotine. The bacterium showed chemotaxis towards root exudates potentially mediated by putrescine, a polyamine compound, to colonize the roots of Nb. Application of the bacterium with the roots of Nb, increased plant biomass and total soluble sugars in the leaves, and promoted lateral root (LR) development as compared to the un-inoculated plants. Confocal analysis using transgenic (DR5:GFP) Arabidopsis showed increased auxin trafficking in the LR of inoculated plants. Upregulation of nicotine biosynthesis genes and genes involved in salicylic acid (SA) and jasmonic acid (JA) signaling in the roots of inoculated plants suggested increased nicotine biosynthesis as a result of bacterial application. An increased JA content in roots and nicotine accumulation in leaves provided evidence on JA-mediated upregulation of nicotine biosynthesis in the bacterized plants. The findings suggested that the bacterial root colonization triggered networking between auxin, SA, and JA to facilitate LR development leading to enhanced plant growth and nicotine biosynthesis in Nb.

Keywords:  Confocal microscopy; Nicotine; Phytohormones; Plant-bacterial interactions; Putrescine; Rhizosphere; Root architecture

DOI:  https://doi.org/10.1016/j.plaphy.2023.01.010
Food Funct. 2023 Jan 19.

Cinnamon (Cinnamomum cassia) water extract improves diarrhea symptoms by changing the gut environment: a randomized controlled trial.

Soo-Yeon Park, Yong Dae Kim, Min Seo Kim, Ki-Tae Kim, Ji Yeon Kim.

Cinnamon is a spice obtained from the bark of Cinnamomum and contains anti-inflammatory ingredients such as coumarin, cinnamaldehyde, and cinnamic acid. This study evaluated the effect of cinnamon water extract (CWE) on the symptoms of subjects with diarrhea in an 8-week randomized controlled trial. Seventy subjects with diarrhea symptoms were randomized and received three capsules of 400 mg CWE or placebo twice daily for 8 weeks. CWE intake significantly increased colonic transit time (p = 0.019) and fecal isobutyric acid (p = 0.008) and spermidine (p = 0.009) contents compared to placebo intake. In contrast, CWE decreased fecal indole (p = 0.032) and agmatine (p = 0.018) contents. Gut microbiota analysis showed increased alpha diversity and significant changes in strains such as Bifidobacterium longum ATCC 55813 (LDA = 1.38) in the CWE group compared with the placebo group. Bifidobacterium longum ATCC 55813 showed a positive correlation with colon transit time and stool phenol and spermidine contents. CWE improved diarrhea symptoms and changed the composition of stools and the gut microbiota. These results indicate that cinnamon intake relieves diarrhea symptoms through metabolic changes due to changes in intestinal microbial groups.

DOI: https://doi.org/10.1039/d2fo01835g
Antibiotics (Basel). 2023 Jan 12. pii: 159. [Epub ahead of print]12(1):

Interconnected Set of Enzymes Provide Lysine Biosynthetic Intermediates and Ornithine Derivatives as Key Precursors for the Biosynthesis of Bioactive Secondary Metabolites.

Paloma Liras, Juan Francisco Martín.

  Bacteria, filamentous fungi, and plants synthesize thousands of secondary metabolites with important biological and pharmacological activities. The biosynthesis of these metabolites is performed by networks of complex enzymes such as non-ribosomal peptide synthetases, polyketide synthases, and terpenoid biosynthetic enzymes. The efficient production of these metabolites is dependent upon the supply of precursors that arise from primary metabolism. In the last decades, an impressive array of biosynthetic enzymes that provide specific precursors and intermediates leading to secondary metabolites biosynthesis has been reported. Suitable knowledge of the elaborated pathways that synthesize these precursors or intermediates is essential for advancing chemical biology and the production of natural or semisynthetic biological products. Two of the more prolific routes that provide key precursors in the biosynthesis of antitumor, immunosuppressant, antifungal, or antibacterial compounds are the lysine and ornithine pathways, which are involved in the biosynthesis of β-lactams and other non-ribosomal peptides, and bacterial and fungal siderophores. Detailed analysis of the molecular genetics and biochemistry of the enzyme system shows that they are formed by closely related components. Particularly the focus of this study is on molecular genetics and the enzymatic steps that lead to the formation of intermediates of the lysine pathway, such as α-aminoadipic acid, saccharopine, pipecolic acid, and related compounds, and of ornithine-derived molecules, such as N5-Acetyl-N5-Hydroxyornithine and N5-anhydromevalonyl-N5-hydroxyornithine, which are precursors of siderophores. We provide evidence that shows interesting functional relationships between the genes encoding the enzymes that synthesize these products. This information will contribute to a better understanding of the possibilities of advancing the industrial applications of synthetic biology.

Keywords:  lysine; ornithine; pipecolic acid; saccharopine; siderophores; α-aminoadipate semialdehyde; α-aminoadipic acid

DOI:  https://doi.org/10.3390/antibiotics12010159
Clin Immunol. 2023 Jan 13. pii: S1521-6616(23)00009-8. [Epub ahead of print]247 109230

Metabolic landscape dysregulation in bronchoalveolar lavage fluid of checkpoint inhibitor pneumonitis.

Wenyi Yu, Yukun He, Ying Shang, Tiantian Guo, Keqiang Wang, Hongge Liang, Jianbo Xue, Xinqian Ma, Xinlin Mu, Ran Li, Zhancheng Gao.

   BACKGROUND: Checkpoint inhibitor pneumonitis (CIP) is a potentially fatal adverse event resulting from immunotherapy in patients with malignant tumors. However, the pathogenesis of CIP remains poorly understood.
METHODS: We collected bronchoalveolar lavage fluid (BALF) from cohorts of patients with CIP, new-onset lung cancer (LC), and idiopathic pulmonary fibrosis (IPF). Non-targeted metabolomics analysis was conducted to analyze metabolic signatures. Flow cytometry was used to evaluate immune cell subsets.
RESULTS: Lymphocytes were predominant in the BALF of patients with CIP. A total of 903 metabolites were identified, among which lipid compounds were the most abundant. In a comparison between patients with CIP and LC, enrichment analysis of the altered metabolites showed suppressed amino sugar metabolism, and spermidine and spermine biosynthesis in the CIP group. Metabolism of alpha linolenic acid, linoleic acid, and their fatty acid derivatives was enriched in the CIP group relative to the IPF group. The twelve metabolites found to be enriched in the CIP group were positively correlated with the proportion of CD8+ T cells. One cluster of BALF metabolites, 57.14% of which were lipid molecules, was inversely correlated with the proportion of natural killer cells.
CONCLUSIONS: In this study, the metabolomic landscape of BALF in patients with CIP was determined. We elucidated suppressed tumor metabolic signatures, enhanced pulmonary inflammatory signaling, and the characteristics of responsible immune cells, which helps to understand the pathogenesis of CIP.

Keywords:  Bronchoalveolar lavage fluid; Checkpoint inhibitor pneumonitis; Flow cytometry; Idiopathic pulmonary fibrosis; Lung cancer; Metabolomics analysis

DOI:  https://doi.org/10.1016/j.clim.2023.109230
Transl Pediatr. 2022 Dec;11(12): 2004-2015

Pathogenesis of bronchopulmonary dysplasia in preterm neonates revealed by an RNA sequencing interaction network analysis.

Fengdan Xu, Yabo Mei, Yaozhong Zhang, Qin Chen, Jinfeng Liao, Xiaoguang He, Zhichun Feng, Xingyun Wang, Ning Li.

   Background: The chronic lung condition known as bronchopulmonary dysplasia (BPD), which primarily affects newborns, especially preterm neonates, is brought on by prolonged oxygen consumption and mechanical ventilation. This case-control study sought to investigate the pathogenesis of BPD in preterm neonates by RNA sequencing (RNA-seq).
Methods: First, RNA-seq samples were collected from 3 BPD and 3 healthy preterm neonates. Based on the sequencing data and microarray data sets, MERGE.57185.1, the key long non-coding RNA (lncRNA), was identified from the differentially expressed lncRNAs and the key module by a weighted gene co-expression network analysis (WGCNA), a Venn diagram, and an expression analysis. Next, the differentially expressed messenger RNAs (mRNAs) and microRNAs (miRNAs) that were strongly correlated to MERGE.57185.1 were identified in the protein-protein interaction networks and underwent a functional enrichment analysis and Spearman correlation analysis. Finally, the mRNA [i.e., eukaryotic translation initiation factor 5A (EIF5A)] and miRNA (i.e., hsa-miR-6833-5p) with the strongest correlations to MERGE.57185.1 were identified as the downstream targets.
Results: Among the 32 genes in the dark-red module and the 158 differentially expressed lncRNAs, 21 overlapping genes were identified. In the gene expression analysis, MERGE.57185.1 (an oncogene) was identified as the key lncRNA in BPD. The results of the multiple bioinformatics analysis showed that the mRNA and the miRNA with the strongest correlations to MERGE.57185.1 were hsa-miR-6833-5p (a suppressor gene) and EIF5A (an oncogene), respectively. Hsa-miR-6833-5p was lowly expressed in the BPD group, while EIF5A was highly expressed in the BPD group.
Conclusions: This study identified 1 key upregulated lncRNA (i.e., MERGE.57185.1) in preterm neonatal BPD, and revealed the MERGE.57185.1/hsa-miR-6833-5p/EIF5A mechanism in preterm neonatal BPD from the lncRNA-miRNA-mRNA network. This key lncRNA gene could serve as a promising diagnostic biomarker for prenatal examinations.

Keywords:   hsa-miR-6833-5p; MERGE.57185.1; Preterm neonatal bronchopulmonary dysplasia (preterm neonatal BPD); RNA sequencing (RNA-seq); eukaryotic translation initiation factor 5A (EIF5A)

DOI:  https://doi.org/10.21037/tp-22-590