Polyamine Metabolism Research Articles

Subtype-specific transcription factors affect polyamine metabolism and the tumor microenvironment in breast cancer.

Polyamines play important roles in cell growth and proliferation. Polyamine metabolism genes are dysregulated in various tumors. Some polyamine metabolism genes are regulated by transcription factors. However, the transcription factors that regulate polyamine metabolism genes have not been completely identified. Additionally, whether any of the transcriptional regulations depend on tumor heterogeneity and the tumor microenvironment has not been investigated. We used bulk RNA-seq data to identify dysregulated polyamine metabolism genes and their transcription factors across breast cancer subtypes. Genes highly correlated with polyamine changes were obtained, and their subtype-specific expressions were checked in tumor microenvironment cells using single-cell RNA (scRNA)-seq data. Gene Ontology enrichmentanalysis was used to explore their molecular functions and biological processes, and survival analysis was used to examine the impact of these genes on therapeutic outcome. We first analyzed the dysregulation of polyamine synthesis, catabolism, and transport in four breast cancer subtypes. Genes such as AGMAT and CAV1 were dysregulated across all subtypes, while APRT, SAT1, and other genes were dysregulated in the more lethal subtypes. Among the dysregulated genes of polyamine metabolism, we focused on three genes (SRM, APRT, and SAT1) and identified their transcription factors (SPI1 and IRF1 correspond to SAT1, and IRF3 corresponds to SRM and APRT). With scRNA-seq data, we verified that these three transcription factors also regulated these three polyamine metabolism genes in the tumor microenvironment. Both bulk RNA-seq and scRNA-seq data indicated that these genes were specifically upregulated in high-risk breast cancer subtypes, such as the basal-like type. High expression of these genes corresponded to worse outcomes in the basal-like subtype under chemotherapy and radiation treatment. Our work identified three subtype-specific transcription factors that regulate three polyamine metabolism genes in high-risk breast cancer subtypes and the tumor microenvironment. Our results deepen the understanding of the role of polyamine metabolism in breast cancer and may help the clinical therapy of advanced breast cancer subtypes.

Exploring polyamine metabolism of the yeast-like fungus, Emergomyces africanus.

Emergomyces africanus is a thermally dimorphic pathogen causing severe morbidity and mortality in immunocompromised patients. Its transition to a pathogenic yeast-like phase in the human host is a notable virulence mechanism. Recent studies suggest polyamines as key players in dimorphic switching, yet their precise functions remain enigmatic. This work aimed to explore polyamine metabolism of two clinical strains of E. africanus (CBS 136260 and CBS 140360) in mycelial and yeast-like phases. In this first report of the polyamine profile of E. africanus, we reveal, using mass spectrometry, spermidine and spermine as the major polyamines in both phases. The secretion of these amines was significantly higher in the pathogenic yeast-like phase than in the mycelial phase, warranting further investigation into the implications thereof on virulence. Additionally, we detected the activity of several polyamine biosynthesis enzymes, including arginine decarboxylase, agmatinase, arginase and ornithine decarboxylase, with significant differences in enzyme expression between morphological phases and strains. Finally, we provide initial evidence for the requirement for spermine, spermidine and putrescine during the thermally induced dimorphic switch of E. africanus, with strain-specific differences in the production of these amines. Overall, our study presents novel insight into polyamine metabolism and its role in dimorphism of E. africanus.

Identification of polyamine metabolism-related prognostic biomarkers for predicting breast cancer prognosis, immune microenvironment, and candidate drugs

In this study, polyamine metabolism related genes (PMRGs) were used to establish a breast cancer (BC) prognostic model. Using PMRGs, TCGA BC samples were divided into cluster1 and cluster2. A 13-gene BC prognostic model was constructed by screening differential genes. High-risk BC patients exhibited heightened immunoinfiltration levels, potentially impeding immunotherapy responses. Drug response predicted that BC patients in the low-risk group might benefit more from chemotherapy and targeted therapy. In conclusion, a novel 13-gene BC prognostic risk model based on PMRGs was established to effectively predict prognosis, immune microenvironment, and drug therapy response in patients with BC.

The effect of silicate on polyamine oxidase genes in Skeletonema dohrnii

By using Skeletonema dohrnii as the experimental algal species, we investigated how silicate concentration impacts the polyamine metabolism of diatoms in our experiment. Three different silicate concentrations were set for cultivation, and Skeletonema dohrnii at the exponential growth phase was selected to analyze basic physiological parameters, polyamine content, and Polyamine oxidase (PAO) gene expression under varying silicate concentrations. Results showed that low silicate concentrations led to reduced growth rate and polyamine content, with down-regulation of PAO gene expression. Conversely, high silicate concentrations did not significantly increase growth rate but did increase polyamine content and up-regulate the PAO gene. These findings suggested that changes in silicate concentration impact the growth rate and polyamine content of Skeletonema dohrnii, with the PAO gene potentially playing a role in regulating the algal response to silicate concentration variations. This study provides a foundation for further exploration of the PAO gene function in Skeletonema dohrnii.

Polyamines mediate cellular energetics and lipid metabolism through mitochondrial respiration to facilitate virus replication.

Polyamines are critical cellular components that regulate a variety of processes, including translation, cell cycling, and nucleic acid metabolism. The polyamines, putrescine, spermidine, and spermine, are found abundantly within cells and are positively-charged at physiological pH. Polyamine metabolism is connected to distinct other metabolic pathways, including nucleotide and amino acid metabolism. However, the breadth of the effect of polyamines on cellular metabolism remains to be fully understood. We recently demonstrated a role for polyamines in cholesterol metabolism, and following these studies, we measured the impact of polyamines on global lipid metabolism. We find that lipid droplets increase in number and size with polyamine depletion. We further demonstrate that lipid anabolism is markedly decreased, and lipid accumulation is due to reduced mitochondrial fatty acid oxidation. In fact, mitochondrial structure and function are largely ablated with polyamine depletion. To compensate, cells depleted of polyamines switch from aerobic respiration to glycolysis in a polyamine depletion-mediated Warburg-like effect. Finally, we show that inhibitors of lipid metabolism are broadly antiviral, suggesting that polyamines and lipids are promising antiviral targets. Together, these data demonstrate a novel role for polyamines in mitochondrial function, lipid metabolism, and cellular energetics.

LsMYB44 and LsWRKY12 regulate endogenous γ-aminobutyric acid (GABA) accumulation in fresh-cut stem lettuce

GABA is able to increase resistance to biotic and abiotic stresses in fresh-cut fruits and vegetables. Therefore, the objective of this research was to explore the potential regulatory mechanisms of γ-aminobutyric acid (GABA) accumulation in fresh-cut stem lettuce following GABA treatment. The evidence showed that exogenous GABA stimulated the GABA shunt by elevating glutamate levels, the activities of GABA transaminase (GABA-T) and glutamate decarboxylase (GAD). Similarly, GABA stimulated polyamine metabolism by increasing the activities of 4-amino aldehyde dehydrogenase (AMADH), polyamine oxidase (PAO) and diamine oxidase (DAO), as well as elevating free polyamines, arginine and ornithine levels. Subsequently, GABA application up-regulated the expression of GABA shunt genes and polyamine metabolism genes. Additionally, GABA treatment resulted in the down-regulation of LsMYB44 and LsWRKY12 expressions. Notably, LsMYB44 bound to MYB binding sites in the LsGAD, LsGABAT1, LsADC1, LsPAO2, LsALDH7B4 promoters and repressed transcription of these genes. The interaction between LsMYB44 and LsWRKY12 was associated with the transcriptional repression of polyamine metabolism and GABA shunt genes by LsMYB44. In conclusion, LsMYB44 and LsWRKY12 downregulated the transcription of key genes of GABA shunt and polyamine metabolism in fresh-cut lettuce. This downregulation, however, was alleviated by the application of GABA, thereby promoting endogenous GABA accumulation.

Single-cell expression and immune infiltration analysis of polyamine metabolism in breast cancer

Breast cancer is one of the most threatening women health diseases worldwide and its molecular heterogeneity offers a range of response to therapy. The role of polyamine metabolism is receiving increasing attention. Polyamine metabolism not only plays an important role in the occurrence and development of breast cancer, but also interacts with tumor immune microenvironment. In this work, we applied single-cell RNA-sequencing (scRNA-seq) and systems immunological approaches to interrogate immune cell infiltration gene-to-gene co-expressions in the bulk tumor transcriptomes of breast cancer. We acquired breast cancer sample data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO), evaluated the infiltration status of 22 immune cell types using CIBERSORTx tool, respectively. By leveraging the Retrospective Breast sample of various technologies including gene expression and methylation, we identified 46 breast cancer proliferation-associated co-expression modules using weighted gene coexpression network analysis (WGCNA) approach along with machine learning models which in turn delineated single cell level expressions features that these selected module possessed. We observed substantial cellular heterogeneity in the breast cancer microenvironment, where lineage-specific gene expression patterns were highly associated with tumor progression. Moreover, we also identified the gene modules correlated with immune cell infiltration level that could function as regulators in response to tumors for immune therapy. Moreover, risk scores were correlated with immune cell function in different patient groups defined by high- and low-risk. The findings of this study shed a new light upon molecular classification prognostic assessment and personalized treatment in breast cancer.

Conservation of the Polyamines Pathway in Ustilaginomycetes A Genomic and Experimental Approach.

Polyamines are organic and aliphatic molecules essential for the growth, development, and survival of both eukaryotes and prokaryotes. In fungi, polyamines play a crucial role in cellular differentiation and pathogenesis. Since fungi and animals are closely related evolutionarily, and fungi can be easily genetically manipulated in the lab, they serve as excellent models for studying polyamine metabolism and the molecular mechanisms controlled by these biomolecules. Although the metabolism of polyamines has been extensively studied in model fungi such as Saccharomyces cerevisiae and Ustilago maydis, the conservation of the polyamine biosynthesis pathway in other Ustilaginomycetes, a class of fungi that includes phytopathogens, saprophytes, mutualists, and mycorrhizae, has not been thoroughly investigated. In this study, using a genomic and bioinformatics approach, we analyzed the conservation of the polyamine biosynthesis pathway in Ustilaginomycetes. Additionally, we confirmed the functional conservation of ornithine decarboxylase (Odc), which is involved in the synthesis of putrescine, one of the most important polyamines in fungi and complex multicellular eukaryotic organisms, using genetics and molecular biology tools. Moreover, we identified the differentially regulated genes by this polyamine in U. maydis. This research provides insights into the similarities and differences in the conservation of the polyamine biosynthesis pathway in fungi, and it expands our understanding of the role of polyamines and the mechanisms regulated by these molecules in eukaryotes.

Divergent Molecular Responses to Heavy Water in Arabidopsis thaliana Compared to Bacteria and Yeast.

Heavy water (D2O) is scarce in nature, and despite its physical similarity to water, D2O disrupts cellular function due to the isotope effect. While microbes can survive in nearly pure D2O, eukaryotes such as Arabidopsis thaliana are more sensitive and are unable to survive higher concentrations of D2O. To explore the underlying molecular mechanisms for these differences, we conducted a comparative proteomic analysis of E. coli, S. cerevisiae, and Arabidopsis after 180 min of growth in a D2O-supplemented media. Shared adaptive mechanisms across these species were identified, including changes in ribosomal protein abundances, accumulation of chaperones, and altered metabolism of polyamines and amino acids. However, Arabidopsis exhibited unique vulnerabilities, such as a muted stress response, lack of rapid activation of reactive oxygen species metabolism, and depletion of stress phytohormone abscisic acid signaling components. Experiments with mutants show that modulating the HSP70 pool composition may promote D2O resilience. Additionally, Arabidopsis rapidly incorporated deuterium into sucrose, indicating that photosynthesis facilitates deuterium intake. These findings provide valuable insights into the molecular mechanisms that dictate differential tolerance to D2O across species and lay the groundwork for further studies on the biological effects of uncommon isotopes, with potential implications for biotechnology and environmental science.

Age-Associated Alterations in the Metabolome of Human Vitreous in Bacterial Endophthalmitis.

Endophthalmitis is a severe inflammatory condition due to intraocular infections that often leads to irreversible blindness. This study aimed to understand the age-dependent metabolic alterations in the vitreous of patients with bacterial endophthalmitis. The study included the vitreous metabolome of patients with bacterial endophthalmitis (group 1, n = 15) and uninfected controls (group 2, n = 14), which were further stratified into three groups according to their age: young (0-30years), middle (31-60years), and elderly (>60years). Vitreous samples were subjected to untargeted metabolomic analysis using high-resolution mass spectrometry (HRMS)m and acquired mass spectrometry data were analyzed using MetaboAnalyst 6.0. The altered metabolites with log2FC of ≥2/≤2, P < 0.05, and variable importance in projection > 1 were considered significant. In a total of 109 endogenous metabolites identified, young and elderly patients with endophthalmitis showed 52 (elevated, 25; reduced, 27; P < 0.05) and 27 (elevated, 19; reduced, 8; P < 0.05) significantly altered metabolites, respectively, compared to their age-matched controls. Additionally, 27 metabolites were differentially expressed in young patients with endophthalmitis compared to the older group. The crucial metabolic pathways dysregulated in the older infected population were de novo purine synthesis and salvage, carnitine, polyamine (spermidine), lipids (prostaglandins), and amino acid (taurine, methionine, histidine) which could possibly be attributed to the increased disease severity and inflammation observed in a clinical setting. Despite the erratic metabolic changes observed in the younger group infected with endophthalmitis when compared to age-matched controls, dysregulation in the specific pathways such as purine, carnitine, arachidonic acid, and polyamine metabolism could possibly alter the immunological exacerbation observed in the older group.

The loss-of-function of AtNATA2 enhances AtADC2-dependent putrescine biosynthesis and priming, improving growth and salinity tolerance in Arabidopsis.

Putrescine (Put) is a promising small molecule-based biostimulant to enhance plant growth and resilience, though its mode of action remains unclear. This study investigated the Put priming effect on Arabidopsis mutant lines (Atadc1, Atadc2, Atnata1, and Atnata2) under control conditions and salinity to understand its role in regulating plant growth. The Atadc2 mutant, characterized by reduced endogenous Put levels, showed insensitivity to Put priming without growth enhancement, which was linked to significant imbalances in nitrogen metabolism, including a high Gln/Glu ratio. Contrarily, the Atnata2 mutant exhibited significant growth improvement and upregulated AtADC2 expression, particularly under Put priming, highlighting these genes' involvement in regulating plant development. Put priming enhanced plant growth by inducing the accumulation of specific polyamines (free, acetylated, conjugated, or bound form) and improving light-harvesting efficiency, particularly in the Atnata2 line. Our findings suggest that AtNATA2 may negatively regulate Put synthesis and accumulation via AtADC2 in the chloroplast, impacting light harvesting in photosystem II (PSII). Furthermore, the Atadc2 mutant line exhibited upregulated AtADC1 but reduced AcPut levels, pointing to a cross-regulation among these genes. The regulation by AtNATA2 on AtADC2 and AtADC2 on AtADC1 could be crucial for plant growth and overall stress tolerance by interacting with polyamine catabolism, which shapes the plant metabolic profile under different growth conditions. Understanding the regulatory mechanisms involving crosstalk between AtADC and AtNATA genes in polyamine metabolism and the connection with certain SMBBs like Put can lead to more effective agricultural practices, improving plant growth, nitrogen uptake, and resilience under challenging conditions.

Illustrate the metabolic regulatory mechanism of Taohong Siwu decoction in ischemic stroke by mass spectrometry imaging.

Metabolic dysregulation in the ischemic region has been increasingly recognized as a contributing factor to ischemic stroke pathogenesis. Taohong Siwu decoction (THSWD), a traditional Chinese medicine preparation used to enhance blood circulation, is frequently employed in treating ischemic stroke. However, the metabolic regulatory mechanism underlying the therapeutic effects of THSWD in ischemic stroke remains largely unexplored. In this study, we employed desorption electrospray ionization mass spectrometry imaging (DESI-MSI) to investigate the metabolic changes in the brain tissue of ischemic stroke rat model. Our investigation revealed that 30 metabolites exhibited significant dysregulation in the ischemic brain regions, specifically the cortex and striatum, following ischemic injury. Following the treatment of THSWD, almost all the dysregulated metabolites got different degrees of callback. Further pathway analysis indicated that THSWD might exert its therapeutic effects by restoring energy metabolism, improving neurotransmitter metabolism, recovering polyamine metabolism, and so on. DESI-MSI offers a favorable methodology for investigating the alterations in the spatial distribution and level within the ischemic brain region following treatment with THSWD in ischemic stroke. These findings provide a novel perspective on the underlying mechanisms of the efficacy of THSWD in ischemic stroke treatment.

Single-cell omics and machine learning integration to develop a polyamine metabolism-based risk score model in breast cancer patients

BackgroundBreast cancer remains the leading malignant neoplasm among women globally, posing significant challenges in terms of treatment and prognostic evaluation. The metabolic pathway of polyamines is crucial in breast cancer progression, with a strong association to the increased capabilities of tumor cells for proliferation, invasion, and metastasis.MethodsWe used a multi-omics approach combining bulk RNA sequencing and single-cell RNA sequencing (scRNA-seq) to study polyamine metabolism. Data from The Cancer Genome Atlas, Gene Expression Omnibus, and Genotype-Tissue Expression identified 286 differentially expressed genes linked to polyamine pathways in breast cancer. These genes were analyzed using univariate COX and machine learning algorithms to develop a prognostic scoring algorithm. Single-cell RNA sequencing validated the model by examining gene expression heterogeneity at the cellular level.ResultsOur single-cell analyses revealed distinct subpopulations with different expressions of genes related to polyamine metabolism, highlighting the heterogeneity of the tumor microenvironment. The SuperPC model (a constructed risk score) demonstrated high accuracy when predicting patient outcomes. The immune profiling and functional enrichment analyses revealed that the genes identified play a crucial role in cell cycle control and immune modulation. Single-cell validation confirmed that polyamine metabolism genes were present in specific cell clusters. This highlights their potential as therapeutic targets.ConclusionsThis study integrates single cell omics with machine-learning to develop a robust scoring model for breast cancer based on polyamine metabolic pathways. Our findings offer new insights into tumor heterogeneity, and a novel framework to personalize prognosis. Single-cell technologies are being used in this context to enhance our understanding of the complex molecular terrain of breast cancer and support more effective clinical management.

The effect of spermidine supplementation on polyamine metabolism and Fusarium infection in Linum usitatissimum

Flax (Linum usitatissimum) is a valuable industrial crop in temperate climate zones. However, the prevalence of fungal diseases, particularly those caused by Fusarium oxysporum sp. linii, poses a substantial threat, leading to significant crop losses and diminished interest in flax cultivation. In this study, flax plants were treated with spermidine and subsequently infected with Fusarium oxysporum to investigate multiple aspects: (1) the uptake of exogenous spermidine by the plants, (2) the impact of this uptake on the levels of other polyamines and the expression of polyamine biosynthesis genes, and (3) the effects of fungal infection on these parameters. The results demonstrated that flax plants effectively absorb spermidine, leading to substantial changes in the levels of polyamines and the expression of related genes in both roots and shoots. Notably, spermidine treatment resulted in significant alterations in the levels of putrescine and spermine, as well as in the transcript levels of key genes involved in polyamine biosynthesis. Moreover, Fusarium oxysporum infection itself induced changes in polyamine content and gene expression, which varied between root and shoot tissues. When spermidine-treated plants were infected with Fusarium oxysporum, a more complex response was observed, characterized by modifications in polyamine levels and gene expression that suggest an enhanced defense mechanism against the pathogen. These findings indicate that polyamine treatment not only affects the infection process but also modulates the plant's internal polyamine metabolism and gene expression, contributing to an improved resistance to fungal attack. This study highlights the potential of spermidine as a protective agent in flax and provides a foundation for further exploration of polyamine-related defense mechanisms.

Supplementation of spermidine enhances the quality of postovulatory aged porcine oocytes

BackgroundSpermidine (SPD) is an intermediate compound in the polyamine metabolism which takes critical part in a variety of cellular processes. In particular, it has been reported to exert anti-aging effects, suppress the age-related diseases, and extend lifespan across species. However, whether it has the favorable influence on the quality of postovulatory aged oocytes remains elusive.MethodsImmunostaining and fluorescence intensity measurement were used to evaluate the effects of postovulatory aging and SPD supplementation on the oocyte fragmentation, spindle/chromosome structure, actin polymerization, dynamics of cortical granules (CGs) and ovastacin, mitochondrial distribution and function, as well as autophagy levels. In addition, in vitro sperm binding assay and in vitro fertilization (IVF) experiment were applied to assess the impacts of postovulatory aging and SPD supplementation on the sperm binding ability and fertilization capacity of oocytes.ResultsHere, we showed that supplementation of SPD during postovulatory aging could relieve the deterioration of porcine oocytes. Specifically, we found that postovulatory aging impaired the oocyte quality by damaging the morphological integrity of oocytes, maintenance of spindle/chromosome structure, and dynamics of actin cytoskeleton. Postovulatory aging also weakened the sperm binding ability and fertilization capacity of oocytes by compromising the distribution pattern of CGs and their content ovastacin. Notably, supplementation of SPD attenuated these defects in postovulatory aged porcine oocytes via strengthening mitochondrial function, eliminating excessive reactive oxygen species (ROS), inhibiting apoptosis, and enhancing autophagy levels.ConclusionAltogether, our findings demonstrate that SPD supplementation is a feasible approach to ameliorate the quality of postovulatory aged oocytes, which can be potentially applied to the human assisted reproductive technology (ART) and in vitro production of animal embryos.

Preinoculation with Bradyrhizobium japonicum enhances the salt tolerance of Glycine max seedlings by regulating polyamine metabolism in roots

Rhizobia are common symbiotic microorganisms in the root system of leguminous plants that can usually provide nitrogen to the host through nitrogen fixation. Studies have shown that rhizobium-preinoculated soybean plants usually exhibit improved salt tolerance, but the underlying mechanism is not fully understood. In this paper, transcriptome sequencing (RNA-seq) revealed that preinoculation with rhizobia affected polyamine (PA) metabolism in soybean roots. The assay of PA contents showed that preinoculation with rhizobia significantly increased the putrescine (Put) content in roots and leaves during short-term salt treatment (0–5 d). Long-term salt treatment (5–7 d) resulted in a high Put content and significantly increased Spm and Spd contents, resulting in a rapid increase in the Put/(Spd + Spm) ratio (0–5 d) and subsequent decrease. Moreover, rhizobium preinoculation of soybean plants resulted in increased contents of conjugated and bound PAs under salt stress. Further transcriptome sequencing, PA contents, PA synthase expression and activity analysis revealed that GmADC may be a key gene related to salt tolerance in rhizobium-preinoculated soybean plants, and the GmADC-overexpressing soybean hairy-root composite plants exhibited less ROS damage, lower Cl−/NO3− ratios and Na+/K+ ratios, and stabilized ion homeostasis. Taken together, preinoculation with rhizobia increased the expression level and enzyme activity of arginine decarboxylase (ADC) in soybean roots, increased the content of Put in roots and leaves, and increased the content of conjugated and bound PAs in soybean plants, thereby alleviating the oxidative and ionic injuries of soybean plants and enhancing the salt tolerance.

Intestinal Lactobacillus murinus-derived small RNAs target porcine polyamine metabolism

Gut microbiota plays a vital role in host metabolism; however, the influence of gut microbes on polyamine metabolism is unknown. Here, we found germ-free models possess elevated polyamine levels in the colon. Mechanistically, intestinal Lactobacillus murinus-derived small RNAs in extracellular vesicles down-regulate host polyamine metabolism by targeting the expression of enzymes in polyamine metabolism. In addition, Lactobacillus murinus delays recovery of dextran sodium sulfate-induced colitis by reducing polyamine levels in mice. Notably, a decline in the abundance of small RNAs was observed in the colon of mice with colorectal cancer (CRC) and human CRC specimens, accompanied by elevated polyamine levels. Collectively, our study identifies a specific underlying mechanism used by intestinal microbiota to modulate host polyamine metabolism, which provides potential intervention for the treatment of polyamine-associated diseases.

GABA promotes peroxisome proliferation in Triticum monococcum leaves.

Although peroxisomes are integral for both primary and secondary metabolism, how developmental changes affect activity of peroxisomes remains poorly understood. Here, we used published RNA-seq data to analyze the expression patterns of genes encoding 21 peroxisome metabolic pathways at successive developmental stages of Zea mays and Oryza sativa. Photorespiration was the most represented pathway in adult leaf relative to the juvenile stages. Components of reactive oxygen species (ROS)/reactive nitrogen species (RNS) metabolism, NADPH regeneration, and catabolism of polyamines were also enriched at later stages of leaf differentiation. The most commonly upregulated gene in differentiated leaves across all datasets of both species was BETAINE ALANINE DEHYDROGENASE (BADH). BADH functions in catabolism of polyamines where it converts 4-aminobutyraldehyde (ABAL) to 4-aminobutyrate (GABA). We tested the outcome of RNA-seq analysis by qRT-PCR in developing Triticum monococcum ssp. monococcum (Einkorn) seedlings. Consistent with the outcomes of RNA-seq analysis, transcription of BADH and CATALASE3 (CAT3) were upregulated in older seedlings. CAT3 is an essential peroxisome biogenesis factor and a key enzyme of ROS homeostasis. Furthermore, exogenous application of GABA resulted in higher peroxisome abundance and transcriptional upregulation of BADH and a gene encoding another peroxisome biogenesis factor responsible for peroxisome fission, PEROXIN11C (PEX11C), in leaves. We propose that GABA contributes to regulation of peroxisome fission machinery during leaf differentiation.

MO44-4 The level of gene expression of polyamine metabolism proteins in human prostate cancer and benign prostatic hyperplasia

MO44-4 The level of gene expression of polyamine metabolism proteins in human prostate cancer and benign prostatic hyperplasia

Inactivation of spermine synthase in mice causes osteopenia due to reduced osteoblast activity.

Spermine synthase, encoded by the SMS gene, is involved in polyamine metabolism, as it is required for the synthesis of spermine from its precursor molecule spermidine. Pathogenic variants of SMS are known to cause Snyder-Robinson syndrome (SRS), an X-linked recessive disorder causing various symptoms, including intellectual disability, muscular hypotonia, infertility, but also skeletal abnormalities, such as facial dysmorphisms and osteoporosis. Since the impact of a murine SMS deficiency has so far only been analyzed in Gy mice, where a large genomic deletion also includes the neighboring Phex gene, there is only limited knowledge about the potential role of SMS in bone cell regulation. In the present manuscript, we describe 2 patients carrying distinct SMS variants, both diagnosed with osteoporosis. Whereas the first patient displayed all characteristic hallmarks of SRS, the second patient was initially diagnosed, based on laboratory findings, as a case of adult-onset hypophosphatasia. To study the impact of SMS inactivation on bone remodeling, we took advantage of a newly developed mouse model carrying a pathogenic SMS variant (p.G56S). Compared to their wildtype littermates, 12-wk-old male SMSG56S/0 mice displayed reduced trabecular bone mass and cortical thickness, as assessed by μCT analysis of the femur. This phenotype was histologically confirmed by the analysis of spine and tibia sections, where we also observed a moderate enrichment of non-mineralized osteoid in SMSG56S/0 mice. Cellular and dynamic histomorphometry further identified a reduced bone formation rate as a main cause of the low bone mass phenotype. Likewise, primary bone marrow cells from SMSG56S/0 mice displayed reduced capacity to form a mineralized matrix ex vivo, thereby suggesting a cell-autonomous mechanism. Taken together, our data identify SMS as an enzyme with physiological relevance for osteoblast activity, thereby demonstrating an important role of polyamine metabolism in the control of bone remodeling.