bims-polyam 2023-10-29 papers

bims-polyam

Biomed News

on Polyamines

Issue of 2023‒10‒29
eleven papers selected by
Sebastian J. Hofer, University of Graz

Polyamines in Ovarian Aging and Disease.
A bacterial spermidine biosynthetic pathway via carboxyaminopropylagmatine.
Specific Gene Expression in Pseudomonas Putida U Shows New Alternatives for Cadaverine and Putrescine Catabolism.
Polyamine signaling communications play a key role in regulating the pathogenicity of Dickeya fangzhongdai.
Melatonin alleviates Hg toxicity by modulating redox homeostasis and the urea cycle in moss.
Changes in Whole Blood Polyamine Levels and Their Background in Age-Related Diseases and Healthy Longevity.
Investigation into the Relationship between Spermidine Degradation and Phenolic Compounds Biosynthesis in Barley Seedlings under Ultraviolet B Stress.
Impact of COVID-19 on sperm quality and the prostaglandin and polyamine systems in the seminal fluid.
Unmasking metabolic dependencies in pancreatic cancer: aberrant polyamine synthesis as a promising new therapeutic target.
Eggs of the mosquito Aedes aegypti survive desiccation by rewiring their polyamine and lipid metabolism.
Polyamine-containing natural products: structure, bioactivity, and biosynthesis.

Int J Mol Sci. 2023 Oct 18. pii: 15330. [Epub ahead of print]24(20):

Polyamines in Ovarian Aging and Disease.

Bo Kang, Xin Wang, Xiaoguang An, Chengweng Ji, Weikang Ling, Yuxin Qi, Shuo Li, Dongmei Jiang.

  Ovarian aging and disease-related decline in fertility are challenging medical and economic issues with an increasing prevalence. Polyamines are a class of polycationic alkylamines widely distributed in mammals. They are small molecules essential for cell growth and development. Polyamines alleviate ovarian aging through various biological processes, including reproductive hormone synthesis, cell metabolism, programmed cell death, etc. However, an abnormal increase in polyamine levels can lead to ovarian damage and promote the development of ovarian disease. Therefore, polyamines have long been considered potential therapeutic targets for aging and disease, but their regulatory roles in the ovary deserve further investigation. This review discusses the mechanisms by which polyamines ameliorate human ovarian aging and disease through different biological processes, such as autophagy and oxidative stress, to develop safe and effective polyamine targeted therapy strategies for ovarian aging and the diseases.

Keywords:  aging; autophagy; cancer; disease; ovary; polyamine

DOI:  https://doi.org/10.3390/ijms242015330
Sci Adv. 2023 Oct 27. 9(43): eadj9075

A bacterial spermidine biosynthetic pathway via carboxyaminopropylagmatine.

Huachao Xi, Xiaoqun Nie, Fang Gao, Xinxin Liang, Hu Li, Haiyan Zhou, Yujie Cai, Chen Yang.

Spermidine, a ubiquitous polyamine, is known to be required for critical physiological functions in bacteria. Two principal pathways are known for spermidine biosynthesis, both of which involve aminopropylation of putrescine. Here, we identified a spermidine biosynthetic pathway via a previously unknown metabolite, carboxyaminopropylagmatine (CAPA), in a model cyanobacterium Synechocystis sp. PCC 6803 through an approach combining 13C and 15N tracers, metabolomics, and genetic and biochemical characterization. The CAPA pathway starts with reductive condensation of agmatine and l-aspartate-β-semialdehyde into CAPA by a previously unknown CAPA dehydrogenase, followed by decarboxylation of CAPA to form aminopropylagmatine, and ends with conversion of aminopropylagmatine to spermidine by an aminopropylagmatine ureohydrolase. Thus, the pathway does not involve putrescine and depends on l-aspartate-β-semialdehyde as the aminopropyl group donor. Genomic, biochemical, and metagenomic analyses showed that the CAPA-pathway genes are widespread in 15 different phyla of bacteria distributed in marine, freshwater, and other ecosystems.

DOI: https://doi.org/10.1126/sciadv.adj9075
Genes (Basel). 2023 Sep 30. pii: 1897. [Epub ahead of print]14(10):

Specific Gene Expression in Pseudomonas Putida U Shows New Alternatives for Cadaverine and Putrescine Catabolism.

Luis Getino, Alejandro Chamizo-Ampudia, José Luis Martín, José María Luengo, Carlos Barreiro, Elías R Olivera.

  Pseudomonas putida strain U can be grown using, as sole carbon sources, the biogenic amines putrescine or cadaverine, as well as their catabolic intermediates, ɣ-aminobutyrate or δ-aminovalerate, respectively. Several paralogs for the genes that encode some of the activities involved in the catabolism of these compounds, such as a putrescine-pyruvate aminotransferase (spuC1 and spuC2 genes) and a ɣ-aminobutyrate aminotransferase (gabT1 and gabT2 genes) have been identified in this bacterium. When the expression pattern of these genes is analyzed by qPCR, it is drastically conditioned by supplying the carbon sources. Thus, spuC1 is upregulated by putrescine, whereas spuC2 seems to be exclusively induced by cadaverine. However, gabT1 increases its expression in response to different polyamines or aminated catabolic derivatives from them (i.e., ɣ-aminobutyrate or δ-aminovalerate), although gabT2 does not change its expression level concerning no-amine unrelated carbon sources (citrate). These results reveal differences between the mechanisms proposed for polyamine catabolism in P. aeruginosa and Escherichia coli concerning P. putida strain U, as well as allow a deeper understanding of the enzymatic systems used by this last strain during polyamine metabolism.

Keywords:  Pseudomonas putida; amines; cadaverine; polyamines degradation pathways; putrescine; putrescine-pyruvate aminotransferase (SpuC); ɣ-aminobutyrate (GABA); ɣ-aminobutyrate aminotransferase (GabT); δ-aminovalerate (DAVA)

DOI:  https://doi.org/10.3390/genes14101897
Microbiol Spectr. 2023 Oct 24. e0196523

Polyamine signaling communications play a key role in regulating the pathogenicity of Dickeya fangzhongdai.

Congcong Xie, Weihan Gu, Zhongqiao Chen, Zhibin Liang, Shufen Huang, Lian-Hui Zhang, Shaohua Chen.

  Dickeya fangzhongdai is a devastating bacterial pathogen infecting a wide range of crops and ornamental plants worldwide. As a newly identified bacterial species in 2016, the regulatory mechanisms that govern its virulence are still a mystery. In this study, we explored the potential roles of polyamine-mediated cell-to-cell communication in regulation of D. fangzhongdai virulence. Null mutation of speA and speC in D. fangzhongdai strain ZXC1, which encodes polyamine biosynthesis through arginine and ornithine pathways, respectively, dramatically reduced bacterial motility, decreased production of plant cell wall degradation (PCWD) enzymes, and attenuated the bacterial virulence on taro and potato. We then tested the effect of various polyamine molecules in the restoration of the mutant phenotypes and showed that putrescine was the most potent signal in the regulation of virulence traits in strain ZXC1. In addition, we found that taro extract contained active signals to rescue putrescine-deficient phenotypes. High-performance liquid chromatography mass spectrometry analysis validated the speA was essential for production of putrescine in D. fangzhongdai ZXC1. We further showed that the putrescine transporters PotF and PlaP are required for putrescine-mediated cell-to-cell communication and virulence against taro and potato tubers. quantitative reverse transcription-PCR analysis demonstrated that putrescine influences the pathogenicity of D. fangzhongdai ZXC1 by regulating the expression of PCWD enzymes, bacterial chemotaxis, and flagellar-related genes. The findings from this study shed a new light for elucidating the pathogenic mechanisms of D. fangzhongdai and present useful clues for developing relevant disease control strategies. IMPORTANCE Dickeya fangzhongdai is a newly identified plant bacterial pathogen with a wide host range. A clear understanding of the cell-to-cell communication systems that modulate the bacterial virulence is of key importance for elucidating its pathogenic mechanisms and for disease control. In this study, we present evidence that putrescine molecules from the pathogen and host plants play an essential role in regulating the bacterial virulence. The significance of this study is in (i) demonstrating that putrescine signaling system regulates D. fangzhongdai virulence mainly through modulating the bacterial motility and production of PCWD enzymes, (ii) outlining the signaling and regulatory mechanisms with which putrescine signaling system modulates the above virulence traits, and (iii) validating that D. fangzhongdai could use both arginine and ornithine pathways to synthesize putrescine signals. To our knowledge, this is the first report to show that putrescine signaling system plays a key role in modulating the pathogenicity of D. fangzhongdai.

Keywords:  Dickeya fangzhongdai; bacterial motility; pathogenicity; plant cell wall-degrading enzymes; polyamines

DOI:  https://doi.org/10.1128/spectrum.01965-23
Sci Total Environ. 2023 Oct 20. pii: S0048-9697(23)06585-3. [Epub ahead of print]907 167958

Melatonin alleviates Hg toxicity by modulating redox homeostasis and the urea cycle in moss.

Wen-Yue Hu, Hao-Tian Mao, Xiao-Yan Yin, Jing-Yi Chen, An-Qi He, Lin-Yan Huang, Zhong-Wei Zhang, Shu Yuan, Ming Yuan, Yan-Qiu Su, Yang-Er Chen.

  Mercury (Hg) is a highly toxic metal and can cause severe damage to many organisms under natural conditions. As an effective free radical scavenger and antioxidant, Melatonin (MT) has played important protective roles in alleviating oxidative damage caused by environmental cues including heavy metal stress in plants. However, the detailed mechanisms of melatonin in alleviating Hg toxicity still remain unclear in plants. Our results showed that the application of melatonin greatly reduced the concentrations of total and intracellular Hg in Taxiphyllum taxirameum. Meanwhile, melatonin significantly improved the antioxidant capacity and thus alleviated oxidative damage to the chloroplasts of T. taxirameum under Hg stress. Metabolic pathway analysis further revealed that melatonin-treated plants exhibited higher levels of 48 metabolites, including sugars, amino acids, and lipids, than non-melatonin-treated plants under Hg stress. Additionally, we further found that melatonin addition greatly improved the concentrations of four organic acids and three amino acids (Orn, Cit and Arg) related to the urea cycle, and thereby changed the levels of putrescine (Put) and spermidine (Spd) in T. taxirameum exposed to Hg stress. Further experiments showed that the high concentration of Put dramatically caused oxidative damage under Hg stress, while Spd effectively alleviated Hg toxicity in T. taxirameum. Taken together, this study provides new insight into the underlying mechanisms of melatonin in alleviating heavy metal toxicity in plants.

Keywords:  Antioxidant; Melatonin; Mercury; Polyamines; Urea cycle

DOI:  https://doi.org/10.1016/j.scitotenv.2023.167958
Biomedicines. 2023 Oct 18. pii: 2827. [Epub ahead of print]11(10):

Changes in Whole Blood Polyamine Levels and Their Background in Age-Related Diseases and Healthy Longevity.

Kuniyasu Soda.

  The relationship between polyamines and healthy longevity has received much attention in recent years. However, conducting research without understanding the properties of polyamines can lead to unexpected pitfalls. The most fundamental consideration in conducting polyamine studies is that bovine serum used for cell culture contains bovine serum amine oxidase. Bovine serum amine oxidase, which is not inactivated by heat treatment, breaks down spermine and spermidine to produce the highly toxic aldehyde acrolein, which causes cell damage and activates autophagy. However, no such enzyme activity has been found in humans. Polyamine catabolism does not produce toxic aldehydes under normal conditions, but inflammation and some pathogens provoke an inducible enzyme, spermine oxidase, which only breaks down spermine to produce acrolein, resulting in cytotoxicity and the activation of autophagy. Therefore, spermine oxidase activation reduces spermine concentration and the ratio of spermine to spermidine, a feature recently reported in patients with age-related diseases. Spermine, which is increased by a long-term, continuous high polyamine diet, suppresses aberrant gene methylation and the pro-inflammatory status that progress with age and are strongly associated with the development of several age-related diseases and senescence. Changes in spermine concentration and the spermine/spermidine ratio should be considered as indicators of human health status.

Keywords:  LFA-1; age-related disease; gene methylation; inflammation; lifespan extension; polyamine; polyamine-rich food; spermidine; spermine

DOI:  https://doi.org/10.3390/biomedicines11102827
Plants (Basel). 2023 Oct 11. pii: 3533. [Epub ahead of print]12(20):

Investigation into the Relationship between Spermidine Degradation and Phenolic Compounds Biosynthesis in Barley Seedlings under Ultraviolet B Stress.

Chong Xie, Yahui Zhu, Chaoqun Leng, Qiaoe Wang, Pei Wang, Runqiang Yang.

  Barley germination under ultraviolet B (UV-B) illumination stress induces effective accumulation of phenolic compounds in the barley. Spermidine can enhance the biosynthesis of phenolic compounds and alleviate the oxidative damage caused by UV-B. To better understand the function of spermidine, inhibitors of enzymes that are involved in the degradation of spermidine and the synthesis of gamma-aminobutyric acid (GABA), the product of spermidine degradation, were applied to barley germinated under UV-B treatment. The results showed a more severe oxidative damage, and a decrease in phenolic acid contents were observed when spermidine degradation was inhibited. However, GABA application did attenuate an increase in electrolyte permeability and MDA content caused by UV-B induced oxidative damage and improved the respiration rate. Meanwhile, GABA application can elevate the accumulation of phenolic compounds by ca. 20%, by elevating the activities of some key enzymes. Furthermore, the application of GABA, together with the inhibitor of spermidine degradation, can alleviate its suppression of the synthesis of phenolic acids, and resistance to UV-B stress. In conclusion, spermidine alleviated oxidative damage and enhanced the accumulation of phenolic compounds using its degradation product.

Keywords:  barley seedling; gamma-aminobutyric acid; phenolic compounds; spermidine

DOI:  https://doi.org/10.3390/plants12203533
Andrology. 2023 Oct 24.

Impact of COVID-19 on sperm quality and the prostaglandin and polyamine systems in the seminal fluid.

María Eugenia Matzkin, Celina Beguerie, Ignacio De Zuñiga, Gustavo Martinez, Mónica Beatriz Frungieri.

  BACKGROUND: The implications of SARS-CoV-2 infection on male fertility remain largely unknown. Besides their well-known pro- and anti-inflammatory actions, prostaglandins and polyamines are present in semen, where they play key roles in sperm quality.OBJECTIVES: To analyze semen parameters, oxidative profile and the seminal fluid prostaglandin and polyamine systems in samples collected from individuals without coronavirus disease 2019 diagnosis and men who recovered from coronavirus disease 2019.
MATERIALS AND METHODS: This study compared semen collected from men without positive coronavirus disease 2019 diagnosis with samples obtained from individuals 1-6 months and 7-30 months post SARS-CoV-2 infection. Semen parameters, thiobarbituric acid reactive substances, cyclooxygenase 2 expression by fluorescence immunocytochemistry and immunoblotting, prostaglandin levels by enzyme immunoassay, ornithine decarboxylase activity by a radioactive assay, and polyamine and acetylated polyamine levels by thin-layer chromatography were assessed.
RESULTS: In both groups of semen samples from coronavirus disease 2019 recovered men, sperm vitality, total and progressive sperm motility, and putrescine levels were significantly decreased when compared with samples from the uninfected group. In contrast, lipid peroxidation, leukocyte-associated cyclooxygenase 2 expression, and prostaglandin D2 levels were higher in semen from coronavirus disease 2019 recovered men than in samples from uninfected individuals. While sperm concentration and morphology, ornithine decarboxylase activity, and N-acetylputrescine levels were statistically diminished in semen obtained up to 6 months after coronavirus disease 2019 recovery, these parameters remained unchanged when samples were collected 7-30 months after coronavirus disease 2019 recovery. Coronavirus disease 2019 vaccination did not show negative effects on any of the parameters evaluated.
DISCUSSION AND CONCLUSION: Our work provides insights into the detrimental impact of coronavirus disease 2019 on several sperm parameters, in some cases, even more than a year after SARS-CoV-2 infection, which would be accompanied by alterations in the seminal fluid prostaglandin and polyamine profiles. Therefore, future treatments targeting the prostaglandin and polyamine pathways in coronavirus disease 2019 recovered men could lead to a successful reinstatement of semen parameters.

Keywords:  COVID-19; SARS-CoV-2; polyamines; prostaglandins; semen; spermatozoa

DOI:  https://doi.org/10.1111/andr.13548
Signal Transduct Target Ther. 2023 Oct 27. 8(1): 410

Unmasking metabolic dependencies in pancreatic cancer: aberrant polyamine synthesis as a promising new therapeutic target.

Gerrit Wolters-Eisfeld, Thilo Hackert, Cenap Güngör.

DOI: https://doi.org/10.1038/s41392-023-01662-7
PLoS Biol. 2023 Oct;21(10): e3002342

Eggs of the mosquito Aedes aegypti survive desiccation by rewiring their polyamine and lipid metabolism.

Anjana Prasad, Sreesa Sreedharan, Baskar Bakthavachalu, Sunil Laxman.

Upon water loss, some organisms pause their life cycles and escape death. While widespread in microbes, this is less common in animals. Aedes mosquitoes are vectors for viral diseases. Aedes eggs can survive dry environments, but molecular and cellular principles enabling egg survival through desiccation remain unknown. In this report, we find that Aedes aegypti eggs, in contrast to Anopheles stephensi, survive desiccation by acquiring desiccation tolerance at a late developmental stage. We uncover unique proteome and metabolic state changes in Aedes embryos during desiccation that reflect reduced central carbon metabolism, rewiring towards polyamine production, and enhanced lipid utilisation for energy and polyamine synthesis. Using inhibitors targeting these processes in blood-fed mosquitoes that lay eggs, we infer a two-step process of desiccation tolerance in Aedes eggs. The metabolic rewiring towards lipid breakdown and dependent polyamine accumulation confers resistance to desiccation. Furthermore, rapid lipid breakdown is required to fuel energetic requirements upon water reentry to enable larval hatching and survival upon rehydration. This study is fundamental to understanding Aedes embryo survival and in controlling the spread of these mosquitoes.

DOI: https://doi.org/10.1371/journal.pbio.3002342
Nat Prod Rep. 2023 Oct 24.

Polyamine-containing natural products: structure, bioactivity, and biosynthesis.

Qingshan Long, Wen Zhou, Haibo Zhou, Ying Tang, Wu Chen, Qingshu Liu, Xiaoying Bian.

Covering: 2005 to August, 2023Polyamine-containing natural products (NPs) have been isolated from a wide range of terrestrial and marine organisms and most of them exhibit remarkable and diverse activities, including antimicrobial, antiprotozoal, antiangiogenic, antitumor, antiviral, iron-chelating, anti-depressive, anti-inflammatory, insecticidal, antiobesity, and antioxidant properties. Their extraordinary activities and potential applications in human health and agriculture attract increasing numbers of studies on polyamine-containing NPs. In this review, we summarized the source, structure, classification, bioactivities and biosynthesis of polyamine-containing NPs, focusing on the biosynthetic mechanism of polyamine itself and representative polyamine alkaloids, polyamine-containing siderophores with catechol/hydroxamate/hydroxycarboxylate groups, nonribosomal peptide-(polyketide)-polyamine (NRP-(PK)-PA), and NRP-PK-long chain poly-fatty amine (lcPFAN) hybrid molecules.

DOI: https://doi.org/10.1039/d2np00087c