bims-polyam Biomed News
on Polyamines
Issue of 2024‒09‒08
twelve papers selected by
Sebastian J. Hofer, University of Graz
  1. Impact of polyamine supplementation on GnRH expression, folliculogenesis, and puberty onset in young mice.
  2. A surge in endogenous spermidine is essential for rapamycin-induced autophagy and longevity.
  3. Spermidine controls autophagy during fasting.
  4. A Hybrid Biosynthetic-Catabolic Pathway for Norspermidine Production.
  5. Polyamine oxidation enzymes regulate sexual mating/filamentation and pathogenicity in Sporisorium scitamineum.
  6. Non-Linear Association of Dietary Polyamines with the Risk of Incident Dementia: Results from Population-Based Cohort of the UK Biobank.
  7. Genetically encoded fluorescent sensors for visualizing polyamine levels, uptake, and distribution.
  8. Rejuvenation of the reconstitution potential and reversal of myeloid bias of aged HSCs upon pH treatment.
  9. Retraction: l-Arginine Uptake by Cationic Amino Acid Transporter Promotes Intra-Macrophage Survival of Leishmania donovani by Enhancing Arginase-Mediated Polyamine Synthesis.
  10. Retraction: Corrigendum: L-Arginine uptake by cationic amino acid transporter promotes intra-macrophage survival of Leishmania donovani by enhancing arginase-mediated polyamine synthesis.
  11. Quantitative Spermidine Detection in Cosmetics using an Organic Transistor-based Chemical Sensor.
  12. Spatial Organization of Putrescine Synthesis in Plants.
  1. Theriogenology. 2024 Aug 31. pii: S0093-691X(24)00314-5. [Epub ahead of print]229 202-213
    Impact of polyamine supplementation on GnRH expression, folliculogenesis, and puberty onset in young mice.
    Nayan Anand Mate, Geetika Wadhwa, Rajeev Taliyan, Arnab Banerjee.
      BACKGROUND: The hypothalamic-pituitary-gonadal (HPG) axis is pivotal in regulating reproductive functions, with gonadotropin-releasing hormone (GnRH) acting as a central regulator. Recently, polyamines have been shown to regulate the HPG axis, including GnRH expression and ovarian biology in old and adult rodents. The present study firstly highlights the age-specific variation in the polyamine and their corresponding biosynthetic enzymes in the ovary during aging, and further, the study focuses on the effect of polyamines, putrescine, and agmatine, in young female mice.METHOD AND RESULT: Immunofluorescence analysis revealed age-related differences in the expression of ornithine decarboxylase 1 (ODC1), spermine (SPM), and spermidine (SPD) in the ovaries, with adult mice exhibiting significantly higher expression levels compared to young and old mice. Likewise, qPCR analysis showed the mRNA levels of Odc1, Spermidine synthase (Srm), and Spermine synthase (Sms) show a significant increase in adult ovaries, which is then followed by a significant decline in old age. Histological examination demonstrated morphological alterations in the ovaries with age, including decreased follicle numbers and increased stromal cells in old mice. Furthermore, treatment with putrescine, a polyamine, in young mice resulted in larger ovaries and increased follicle numbers compared to controls. Additionally, serum levels of gonadotropin-releasing hormone (GnRH) and progesterone (P4) were measured, showing elevated levels in polyamine-treated mice. GnRH mRNA expression also increased significantly. Gene expression analysis revealed upregulation of genes associated with folliculogenesis such as Fshr, Bmp15, Gdf9, Amh, Star, Hsdb3, and Plaur in the ovaries and onset of puberty such as Tac2, and Kiss1, and a decrease in Mkrn3 in the hypothalamus of polyamine-treated mice.
    CONCLUSION: This study investigates the effect of polyamines in young immature female mice, shedding light on their role in upregulating GnRH, and enhancing folliculogenesis. Overall, these findings suggest that polyamines play a crucial role in ovarian aging and HPG axis regulation, offering potential therapeutics to reinstate fertility in reproductively challenged individuals.
    Keywords:  Aging; Folliculogenesis; GnRH-I; Polyamine; Puberty
    DOI:  https://doi.org/10.1016/j.theriogenology.2024.07.028
  2. Autophagy. 2024 Aug 30.
    A surge in endogenous spermidine is essential for rapamycin-induced autophagy and longevity.
    Sebastian J Hofer, Ioanna Daskalaki, Mahmoud Abdellatif, Ulrich Stelzl, Simon Sedej, Nektarios Tavernarakis, Guido Kroemer, Frank Madeo.
      Acute nutrient deprivation (fasting) causes an immediate increase in spermidine biosynthesis in yeast, flies, mice and humans, as corroborated in four independent clinical studies. This fasting-induced surge in spermidine constitutes the critical first step of a phylogenetically conserved biochemical cascade that leads to spermidine-dependent hypusination of EIF5A (eukaryotic translation initiation factor 5A), which favors the translation of the pro-macroautophagic/autophagic TFEB (transcription factor EB), and hence an increase in autophagic flux. We observed that genetic or pharmacological inhibition of the spermidine increase by inhibition of ODC1 (ornithine decarboxylase 1) prevents the pro-autophagic and antiaging effects of fasting in yeast, nematodes, flies and mice. Moreover, knockout or knockdown of the enzymes required for EIF5A hypusination abolish fasting-mediated autophagy enhancement and longevity extension in these organisms. Of note, autophagy and longevity induced by rapamycin obey the same rule, meaning that they are tied to an increase in spermidine synthesis. These findings indicate that spermidine is not only a "caloric restriction mimetic" in the sense that its supplementation mimics the beneficial effects of nutrient deprivation on organismal health but that it is also an obligatory downstream effector of the antiaging effects of fasting and rapamycin.
    Keywords:  Aging; MTOR; autophagy; lifespan; rapamycin; spermidine
    DOI:  https://doi.org/10.1080/15548627.2024.2396793
  3. Nat Aging. 2024 Sep 04.
    Spermidine controls autophagy during fasting.
    Anna Kriebs.
      
    DOI:  https://doi.org/10.1038/s43587-024-00710-3
  4. Biochem J. 2024 Sep 04. pii: BCJ20240411. [Epub ahead of print]
    A Hybrid Biosynthetic-Catabolic Pathway for Norspermidine Production.
    Bin Li, Jue Liang, Margaret A Phillips, Anthony J Michael.
      The only known pathway for biosynthesis of the polyamine norspermidine starts from aspartate β-semialdehyde to form the diamine 1,3-diaminopropane, which is then converted to norspermidine via a carboxynorspermidine intermediate. This pathway is found primarily in the Vibrionales order of the γ-Proteobacteria. However, norspermidine is also found in other species of bacteria and archaea, and in diverse single-celled eukaryotes, chlorophyte algae and plants that do not encode the known norspermidine biosynthetic pathway. We reasoned that products of polyamine catabolism could be an alternative route to norspermidine production. 1,3-diaminopropane is formed from terminal catabolism of spermine and spermidine, and norspermidine can be formed from catabolism of thermospermine. We found that the single-celled chlorophyte alga Chlamydomonas reinhardtii thermospermine synthase (CrACL5) did not aminopropylate exogenously-derived 1,3-diaminopropane efficiently when expressed in E. coli. In contrast, it completely converted all E. coli native spermidine to thermospermine. Co-expression in E. coli of the polyamine oxidase 5 from lycophyte plant Selaginella lepidophylla (SelPAO5), together with the CrACL5 thermospermine synthase, converted almost all thermospermine to norspermidine. Although CrACL5 was efficient at aminopropylating norspermidine to form tetraamine norspermine, SelPAO5 oxidizes norspermine back to norspermidine, with the balance of flux being inclined fully to norspermine oxidation. The steady-state polyamine content of E. coli co-expressing thermospermine synthase CrACL5 and polyamine oxidase SelPAO5 was an almost total replacement of spermidine by norspermidine.  We have recapitulated a potential hybrid biosynthetic-catabolic pathway for norspermidine production in E. coli, which could explain norspermidine accumulation in species that do not encode the known aspartate β-semialdehyde-dependent pathway.
    Keywords:  biosynthesis; evolutionary biology; metabolic engineering; polyamines; synthetic biology
    DOI:  https://doi.org/10.1042/BCJ20240411
  5. Mol Plant Pathol. 2024 Sep;25(9): e70003
    Polyamine oxidation enzymes regulate sexual mating/filamentation and pathogenicity in Sporisorium scitamineum.
    Kai Yin, Zhijian Hu, Meiting Yuan, Weidong Chen, Xinping Bi, Guobing Cui, Zhibin Liang, Yi Zhen Deng.
      Sugarcane smut fungus Sporisorium scitamineum produces polyamines putrescine (PUT), spermidine (SPD), and spermine (SPM) to regulate sexual mating/filamentous growth critical for pathogenicity. Besides de novo biosynthesis, intracellular levels of polyamines could also be modulated by oxidation. In this study, we identified two annotated polyamine oxidation enzymes (SsPAO and SsCuAO1) in S. scitamineum. Compared to the wild type (MAT-1), the ss1paoΔ and ss1cuao1Δ mutants were defective in sporidia growth, sexual mating/filamentation, and pathogenicity. The addition of a low concentration of cAMP (0.1 mM) could partially or fully restore filamentation of ss1paoΔ × ss2paoΔ or ss1cuao1Δ × ss2cuao1Δ. cAMP biosynthesis and hydrolysis genes were differentially expressed in the ss1paoΔ × ss2paoΔ or ss1cuao1Δ × ss2cuao1Δ cultures, further supporting that SsPAO- or SsCuAO1-based polyamine homeostasis regulates S. scitamineum filamentation by affecting the cAMP/PKA signalling pathway. During early infection, PUT promotes, while SPD inhibits, the accumulation of reactive oxygen species (ROS) in sugarcane, therefore modulating redox homeostasis at the smut fungus-sugarcane interface. Autophagy induction was found to be enhanced in the ss1paoΔ mutant and reduced in the ss1cuao1Δ mutant. Exogenous addition of cAMP, PUT, SPD, or SPM at low concentration promoted autophagy activity under a non-inductive condition (rich medium), suggesting a cross-talk between polyamines and cAMP signalling in regulating autophagy in S. scitamineum. Overall, our work proves that SsPAO- and SsCuAO1-mediated intracellular polyamines affect intracellular redox balance and thus play a role in growth, sexual mating/filamentation, and pathogenicity of S. scitamineum.
    Keywords:   Sporisorium scitamineum ; copper amine oxidase (CuAO); pathogenesis; polyamine oxidase (PAO); redox; sexual mating/filamentation
    DOI:  https://doi.org/10.1111/mpp.70003
  6. Nutrients. 2024 Aug 20. pii: 2774. [Epub ahead of print]16(16):
    Non-Linear Association of Dietary Polyamines with the Risk of Incident Dementia: Results from Population-Based Cohort of the UK Biobank.
    Mingxia Qian, Na Zhang, Rui Zhang, Min Liu, Yani Wu, Ying Lu, Furong Li, Liqiang Zheng.
      Natural polyamines, including spermidine (SPD), spermine (SPM) and putrescine (PUT), are evolutionarily conserved endogenous molecules crucially involved in central cellular processes. Their physiological importance may extend to the maintenance of cognitive function during aging. However, limited population-based epidemiological studies have explored the link between dietary polyamines and dementia risk. This study was a prospective analysis of 77,092 UK Biobank participants aged ≥ 60 years without dementia at baseline. We used Cox proportional hazard regression models to explore the associations between dietary polyamines and the risk of dementia, and restricted cubic splines to test the non-linear relationships. During a median follow-up of 12 years, 1087 incidents of all-cause dementia cases occurred, including 450 Alzheimer's disease (AD) cases and 206 vascular dementia (VD) cases. The fully adjusted hazard ratios (HRs) for the upper fourth quintile of dietary SPD, in comparison with the lowest quintile of intake, were 0.68 (95% confidence interval [95% CI]: 0.66-0.83) for the risk of all-cause dementia, 0.62 (95% CI: 0.45-0.85) for AD and 0.56 (95% CI: 0.36-0.88) for VD, respectively. A 26% reduction in dementia risk [HR: 0.74, (95% CI: 0.61-0.89)] and a 47% reduction in AD [HR: 0.53, (95%CI: 0.39-0.72)] were observed comparing the third with the lowest quintiles of dietary SPM. Dietary PUT was only associated with a reduced risk of all-cause dementia in the fourth quintile [HR (95% CI): 0.82 (0.68-0.99)]. Reduced risk was not found to be significant across all quintiles. There were 'U'-shaped relationships found between dietary polyamines and all-cause dementia, AD and VD. Stratification by genetic predisposition showed no significant effect modification. Optimal intake of polyamines was linked to a decreased risk of dementia, with no modification by genetic risk. This potentially suggests cognitive benefits of dietary natural polyamines in humans.
    Keywords:  dementia; polyamines; putrescine; spermidine; spermine
    DOI:  https://doi.org/10.3390/nu16162774
  7. bioRxiv. 2024 Aug 22. pii: 2024.08.21.609037. [Epub ahead of print]
    Genetically encoded fluorescent sensors for visualizing polyamine levels, uptake, and distribution.
    Ryo Tamura, Jialin Chen, Marijke De Jaeger, Jacqueline F Morris, David A Scott, Peter Vangheluwe, Loren L Looger.
      Polyamines are abundant and physiologically essential biomolecules that play a role in numerous processes, but are disrupted in diseases such as cancer, and cardiovascular and neurological disorders. Despite their importance, measuring free polyamine concentrations and monitoring their metabolism and uptake in cells in real-time remains impossible due to the lack of appropriate biosensors. Here we engineered, characterized, and validated the first genetically encoded biosensors for polyamines, named iPASnFRs. We demonstrate the utility of iPASnFR for detecting polyamine import into mammalian cells, to the cytoplasm, mitochondria, and the nucleus. We demonstrate that these sensors are useful to probe the activity of polyamine transporters and to uncover biochemical pathways underlying the distribution of polyamines amongst organelles. The sensors powered a high-throughput small molecule compound library screen, revealing multiple compounds in different chemical classes that strongly modulate cellular polyamine levels. These sensors will be powerful tools to investigate the complex interplay between polyamine uptake and metabolic pathways, address open questions about their role in health and disease, and enable screening for therapeutic polyamine modulators.
    DOI:  https://doi.org/10.1101/2024.08.21.609037
  8. Aging Cell. 2024 Sep 05. e14324
    Rejuvenation of the reconstitution potential and reversal of myeloid bias of aged HSCs upon pH treatment.
    Sachin Kumar, Jeffrey D Vassallo, Kalpana J Nattamai, Aishlin Hassan, Angelika Vollmer, Rebekah Karns, Mehmet Sacma, Travis Nemkov, Angelo D'Alessandro, Hartmut Geiger.
      Aged hematopoietic stem cells (HSCs) show reduced reconstitution potential, limiting their use in transplantation settings in the clinic. We demonstrate here that exposure of aged HSCs ex vivo to a pH of 6.9 instead of the commonly used pH of 7.4 results in enhanced HSCs potential that is consistent with rejuvenation, including attenuation of the myeloid bias of aged HSC and restoration of a youthful frequency of epigenetic polarity. Rejuvenation of aged HSCs by pH 6.9 is, at least in part, due to alterations in the polyamine/methionine pathway within pH 6.9 HSCs, and consequently, attenuation of the production of spermidine also attenuated aging of HSCs. Exposure of aged HSCs to pH 6.9, or pharmacological targeting of the polyamine pathway, might thus extend the use of HSCs from aged donors for therapeutic applications.
    Keywords:  aging; hematopoietic stem cells; pH; polyamine; rejuvenation
    DOI:  https://doi.org/10.1111/acel.14324
  9. Front Immunol. 2024 ;15 1474938
    Retraction: l-Arginine Uptake by Cationic Amino Acid Transporter Promotes Intra-Macrophage Survival of Leishmania donovani by Enhancing Arginase-Mediated Polyamine Synthesis.
    Frontiers Editorial Office
      [This retracts the article DOI: 10.3389/fimmu.2017.00839.].
    DOI:  https://doi.org/10.3389/fimmu.2024.1474938
  10. Front Immunol. 2024 ;15 1474944
    Retraction: Corrigendum: L-Arginine uptake by cationic amino acid transporter promotes intra-macrophage survival of Leishmania donovani by enhancing arginase-mediated polyamine synthesis.
    Frontiers Editorial Office
      [This retracts the article DOI: 10.3389/fimmu.2019.03101.].
    DOI:  https://doi.org/10.3389/fimmu.2024.1474944
  11. ChemistryOpen. 2024 Sep 05. e202400098
    Quantitative Spermidine Detection in Cosmetics using an Organic Transistor-based Chemical Sensor.
    Yui Sasaki, Kohei Ohshiro, Miyuki Kato, Hikaru Tanaka, Akari Yamagami, Kazutake Hagiya, Tsuyoshi Minami.
      Spermidine is an essential biomarker related to antiaging. Although the detection of spermidine levels is in high demand in life science fields, easy-to-use analytical tools without sample purification have not yet been fully established. Herein, we propose an organic field-effect transistor-based chemical sensor for quantifying the spermidine concentration in commercial cosmetics. An extended-gate structure was employed for organic field-effect transistor (OFET)-based chemical sensing in aqueous media. A coordination-bond-based sensing system was introduced into the OFET device to visualize the spermidine detection information through changes in the transistor characteristics. The extended-gate-type OFET has shown quantitative responses to spermidine, which indicates sufficient detectability (i. e., the limit of detection for spermidine: 2.3 μM) considering actual concentrations in cosmetics. The applicability of the OFET-based chemical sensor for cosmetic analysis was validated by instrumental analysis using high-performance liquid chromatography. The estimated recovery rates for spermidine in cosmetic ingredient products (108-111 %) suggest the feasibility of cosmetic analysis based on the OFET-based chemical sensor.
    Keywords:  Amines; Cosmetic analysis; Organic transistor; Sensors
    DOI:  https://doi.org/10.1002/open.202400098
  12. Plant Sci. 2024 Aug 28. pii: S0168-9452(24)00259-0. [Epub ahead of print] 112232
    Spatial Organization of Putrescine Synthesis in Plants.
    Kumud Joshi, Sheaza Ahmed, Lingxiao Ge, Arefeh Avestakh, Babatunde Oloyede, Vipaporn Phuntumart, Andrea Kalinoski, Paul F Morris.
      Three plant pathways for the synthesis of putrescine have been described to date. These are the synthesis of putrescine from ornithine, by ornithine decarboxylase (ODC); the synthesis of putrescine from arginine by arginine decarboxylase, agmatine iminohydrolase (AIH) and N-carbamoylputrescine amidohydrolase (NLP1); and arginine decarboxylase and agmatinase. To address how these pathways are organized in plants, we have used transient expression analysis of these genes in the leaves of Nicotiana benthamiana. Brassicas do not have ODC, but the single ODC gene from rice and one of the soybean genes, were localized to the ER. Transient expression of the rice agmatinase gene showed that it was localized to the mitochondria. In A. thaliana there are five isoforms of AIH and three isoforms of NLP1. Stable GFP-tagged transformants of the longest isoforms of AIH and NLP1 showed that both proteins were localized to the ER, but in tissues with chloroplasts, the localization was concentrated to lamellae adjacent to chloroplasts. Transient expression analyses showed that four of the isoforms of AIH and all of the isoforms of NLP1 were localized to the ER. However, AIH.4 was localized to the chloroplast. Combining these results with other published data, reveal that putrescine synthesis is excluded from the cytoplasm and is spatially localized to the chloroplast, ER, and likely the mitochondria. Synthesis of putrescine in the ER may facilitate cell to cell transport via plasmodesmata, or secretion via vesicles. Differential expression of these pathways may enable putrescine-mediated activation of hormone-responsive genes.
    Keywords:  compartmentation Endomplasmic reticulum; polyamines; stress response
    DOI:  https://doi.org/10.1016/j.plantsci.2024.112232
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