S-adenosylmethionine Decarboxylase Research Articles

Functional polyamine metabolic enzymes and pathways encoded by the virosphere

Viruses produce more viruses by manipulating the metabolic and replication systems of their host cells. Many have acquired metabolic genes from ancestral hosts and use the encoded enzymes to subvert host metabolism. The polyamine spermidine is required for bacteriophage and eukaryotic virus replication, and herein, we have identified and functionally characterized diverse phage- and virus-encoded polyamine metabolic enzymes and pathways. These include pyridoxal 5'-phosphate (PLP)-dependent ornithine decarboxylase (ODC), pyruvoyl-dependent ODC and arginine decarboxylase (ADC), arginase, S-adenosylmethionine decarboxylase (AdoMetDC/speD), spermidine synthase, homospermidine synthase, spermidine N-acetyltransferase, and N-acetylspermidine amidohydrolase. We identified homologs of the spermidine-modified translation factor eIF5a encoded by giant viruses of the Imitervirales. Although AdoMetDC/speD is prevalent among marine phages, some homologs have lost AdoMetDC activity and have evolved into pyruvoyl-dependent ADC or ODC. The pelagiphages that encode the pyruvoyl-dependent ADCs infect the abundant ocean bacterium Candidatus Pelagibacter ubique, which we have found encodes a PLP-dependent ODC homolog that has evolved into an ADC, indicating that infected cells would contain both PLP- and pyruvoyl-dependent ADCs. Complete or partial spermidine or homospermidine biosynthetic pathways are found encoded in the giant viruses of the Algavirales and Imitervirales, and in addition, some viruses of the Imitervirales can release spermidine from the inactive N-acetylspermidine. In contrast, diverse phages encode spermidine N-acetyltransferase that can sequester spermidine into its inactive N-acetyl form. Together, the virome-encoded enzymes and pathways for biosynthesis and release or biochemical sequestration of spermidine or its structural analog homospermidine consolidate and expand evidence supporting an important and global role of spermidine in virus biology.

Structure-Activity Relationship Studies of 9-Alkylamino-1,2,3,4-tetrahydroacridines against Leishmania (Leishmania) infantum Promastigotes.

Leishmaniasis is one of the most neglected diseases in modern times, mainly affecting people from developing countries of the tropics, subtropics and the Mediterranean basin, with approximately 350 million people considered at risk of developing this disease. The incidence of human leishmaniasis has increased over the past decades due to failing prevention and therapeutic measures-there are no vaccines and chemotherapy, which is problematic. Acridine derivatives constitute an interesting group of nitrogen-containing heterocyclic compounds associated with numerous bioactivities, with emphasis to their antileishmanial potential. The present work builds on computational studies focusing on a specific enzyme of the parasite, S-adenosylmethionine decarboxylase (AdoMet DC), with several 1,2,3,4-tetrahydro-acridines emerging as potential inhibitors, evidencing this scaffold as a promising building block for novel antileishmanial pharmaceuticals. Thus, several 1,2,3,4-tetrahydroacridine derivatives have been synthesized, their activity against Leishmania (Leishmania) infantum promastigotes evaluated and a structure-activity relationship (SAR) study was developed based on the results obtained. Even though the majority of the 1,2,3,4-tetrahydroacridines evaluated presented high levels of toxicity, the structural information gathered in this work allowed its application with another scaffold (quinoline), leading to the obtention of N1,N12-bis(7-chloroquinolin-4-yl)dodecane-1,12-diamine (12) as a promising novel antileishmanial agent (IC50 = 0.60 ± 0.11 μM, EC50 = 11.69 ± 3.96 μM and TI = 19.48).

Molecular docking and simulation studies of medicinal plant phytochemicals with Leishmania donovani adenosylmethionine decarboxylase

Molecular docking and simulation studies of medicinal plant phytochemicals with Leishmania donovani adenosylmethionine decarboxylase

How Carbon Nanoparticles, Arbuscular Mycorrhiza, and Compost Mitigate Drought Stress in Maize Plant: A Growth and Biochemical Study.

Drought negatively affects crop growth and development, so it is crucial to develop practical ways to reduce these consequences of water scarcity. The effect of the interactive potential of compost (Comp), mycorrhizal fungi (AMF), and carbon nanoparticles (CNPS) on plant growth, photosynthesis rate, primary metabolism, and secondary metabolism was studied as a novel approach to mitigating drought stress in maize plants. Drought stress significantly reduced maize growth and photosynthesis and altered metabolism. Here, the combined treatments Com-AMF or Com-AMF-CNPs mitigated drought-induced reductions in fresh and dry weights. The treatments with AMF or CNPS significantly increased photosynthesis (by 10%) in comparison to the control plants. Results show that soluble sugars were accumulated to maintain the osmotic status of the maize plant under drought stress. The level and metabolism of sucrose, an osmo-protectant, were increased in plants treated with Com (by 30%), which was further increased under the triple effect of Com-AMF-CNPs (40%), compared to untreated plants. This was inconsistent with increased sucrose-phosphate synthase and sucrose-P-synthase activity. The combined treatment Com-AMF-CNPs increased the levels of oxalic and succinic acids (by 100%) and has been reflected in the enhanced levels of amino acids such as the antioxidant and omso-protectant proline. Higher increases in fatty acids by treatment with CNPS were also recorded. Com-AMF-CNPs enhanced many of the detected fatty acids such as myristic, palmitic, arachidic, docosanoic, and pentacosanoic (110%, 30%, 100%, and 130%, respectively), compared to untreated plants. At the secondary metabolism level, sugar and amino acids provide a route for polyamine biosynthesis, where Com-AMF-CNPs increased spermine and spermidine synthases, ornithine decarboxylase, and adenosyl methionine decarboxylase in treated maize. Overall, our research revealed for the first time how Cmo, AMF, and/or CNPS alleviated drought stress in maize plants.

Silicon inhibits gummosis by promoting polyamine synthesis and repressing ethylene biosynthesis in peach.

Silicon is a beneficial element for plant growth, as well as for improving plant resistance to multiple biotic and abiotic stresses. Gummosis is a common harmful disease in peach and is induced by many factors. However, the effect of silicon on gummosis of peach has not been determined yet. In this study, we reported that application of silicon significantly reduced gummosis by regulating biosynthesis of ethylene and polyamines in peach. Ethylene promoted the development of gummosis by inducing the expression of genes encoding cell wall degrading enzymes. While application of different types of polyamines, including spermidine and spermine, dramatically inhibited the occurrence of gummosis. Moreover, polyamines inhibited the ethylene biosynthesis by down-regulating expression of ethylene biosynthetic gene PpACS1 (1-aminocyclopropane -1-carboxylic acid synthase), as well as the enzymatic activity of ACS. We further found that application of silicon significantly restricted the development of gummosis in peach. Exogenous silicon dramatically inhibited expression of PpACS1 and the enzymatic activity of its product to reduce ethylene biosynthesis. Simultaneously, the activity of S-adenosylmethionine decarboxylase, a key enzyme in ployamines biosynthesis, was increased by 9.85% under silicon treatment, resulting in elevated accumulation of polyamines. Thus, our data proved that application of silicon restricted gummosis development by activating ployamines biosynthesis and inhibiting ethylene synthesis in peach.

TMET-09. LOSS OF MAT2A COMPROMISES METHIONINE METABOLISM AND REPRESENTS A VULNERABILITY IN H3K27M MUTANT GLIOMAS

Abstract H3K27-mutant diffuse midline gliomas (DMGs) are defined as grade IV tumors by the World Health Organization. DMGs are inoperable and resistant to chemo/radio therapies. Median survival ranges from 8-11 months, with 2% of patients surviving beyond 5 years. H3K27M mutations lead to global epigenetic and transcriptional reprogramming driven by global loss of negative transcriptional regulator H3K27 trimethylation (H3K27me3). Loss of H3K27me3 is an initiating event in gliomagenesis. This disease lacks appropriate models to predict disease biology and response to treatment. Therefore, we developed a novel syngeneic H3K27M mouse model. An unbiased integrated systems biology approach identified that H3K27M but not isogenic controls relied on the amino acid methionine and the enzyme Methionine Adenosyltransferase 2A (MAT2A). MAT2A is a central regulator of one-carbon metabolism by converting methionine to S-adenosylmethionine (SAM), the universal methyl-donor for protein and nucleotide methylation reactions. In complementary genetic approaches, we applied these findings to patient-derived cell lines with the H3K27M mutation. We hypothesize that MAT2A abrogation, genetic/pharmacological, would alter DMG viability by disrupting the methylome. The current MAT2A sensitivity paradigm is based on Methylthioadenosine Phosphorylase (MTAP) deletion through a synthetic lethal mechanism. We provide a novel mechanism whereby H3K27M cells are sensitive to MAT2A loss, independent of MTAP and through Adenosylmethionine Decarboxylase 1 (AMD1) overexpression disrupting MAT2A regulation. This results in H3K27M cells having lower MAT2A protein levels, conferring a sensitivity by inhibiting residual MAT2A. Genetic/pharmacological aberrations to MAT2A resulted in reduced proliferation. Parallel H3K36me3 ChIP and RNA-sequencing identified loss of oncogenic and developmental transcriptional programs associated with MAT2A loss. In vivo syngeneic and patient-derived xenograft models with both inducible MAT2A knockdown or methionine restricted diets showed extended survival. These results suggest novel interactions between methionine metabolism and the epigenome of H3K27M gliomas and provide evidence that MAT2A, presents exploitable therapeutic vulnerabilities in histone mutant gliomas.

Genome-wide analysis of polyamine biosynthesis genes in wheat reveals gene expression specificity and involvement of STRE and MYB-elements in regulating polyamines under drought

BackgroundPolyamines (PAs) are considered promising biostimulants that have diverse key roles during growth and stress responses in plants. Nevertheless, the molecular basis of these roles by PAs has not been completely realized even now, and unfortunately, the transcriptional analyses of the biosynthesis pathway in various wheat tissues have not been investigated under normal or stress conditions. In this research, the findings of genome-wide analyses of genes implicated in the PAs biosynthesis in wheat (ADC, Arginine decarboxylase; ODC, ornithine decarboxylase; AIH, agmatine iminohydrolase; NPL1, Nitrlase like protein 1; SAMDC, S-adenosylmethionine decarboxylase; SPDS, spermidine synthase; SPMS, spermine synthase and ACL5, thermospermine synthase) are shown.ResultsIn total, thirty PAs biosynthesis genes were identified. Analysis of gene structure, subcellular compartmentation and promoters were discussed. Furthermore, experimental gene expression analyses in roots, shoot axis, leaves, and spike tissues were investigated in adult wheat plants under control and drought conditions. Results revealed structural similarity within each gene family and revealed the identity of two new motifs that were conserved in SPDS, SPMS and ACL5. Analysis of the promoter elements revealed the incidence of conserved elements (STRE, CAAT-box, TATA-box, and MYB TF) in all promoters and highly conserved CREs in >80% of promoters (G-Box, ABRE, TGACG-motif, CGTCA-motif, as1, and MYC). The results of the quantification of PAs revealed higher levels of putrescine (Put) in the leaves and higher spermidine (Spd) in the other tissues. However, no spermine (Spm) was detected in the roots. Drought stress elevated Put level in the roots and the Spm in the leaves, shoots and roots, while decreased Put in spikes and elevated the total PAs levels in all tissues. Interestingly, PA biosynthesis genes showed tissue-specificity and some homoeologs of the same gene family showed differential gene expression during wheat development. Additionally, gene expression analysis showed that ODC is the Put biosynthesis path under drought stress in roots.ConclusionThe information gained by this research offers important insights into the transcriptional regulation of PA biosynthesis in wheat that would result in more successful and consistent plant production.

165 (PB045) - Exploring the role of S-Adenosyl Methionine Decarboxylase (AMD1) in the growth, migration, metabolism and drug-combination profile of non-small cell lung cancer cells

Non-small cell lung cancer (NSCLC) accounts for 85% of lung cancer and is associated with the poorest prognosis and survival. Current chemotherapy against NSCLC is limited to traditional chemotherapy, with a high incidence of adverse effects.

Characterization of different meat flavor compounds in Guangdong small-ear spotted and Yorkshire pork using two-dimensional gas chromatography–time-of-flight mass spectrometry and multi-omics

In China, indigenous pigs are popular due to their excellent meat quality and unique flavor. In this study, the unique flavor was investigated using Guangdong small-ear spotted pig (GD) and their hybrid progeny, which produced high-end pork in the Chinese market. Two-dimensional gas chromatography-time-of-flight mass spectrometry (GC × GC-TOF MS) was used to analyze and quantify volatile organic compounds (VOCs) in the two pork types for identifying the unique flavor of these very popular pigs. The flavor is imparted by alkanes, aldehydes, ketones, and ethers. Flavor imparting compounds mainly include methyl isobutyl ketone, octane, pentane, and 3-ethyl-2, 2-dimethylheptane. High levels of volatilization of such compounds generated ethereal, acetonic, sweet, and green odors in the pork of GD. Hybrid offspring of Chinese and Western pig breeds can also inherit such special aromas, which are sometimes even more intense, with increased meat yield. Multi-omics analysis of the transcriptome and metabolome showed that AMD1 (Adenosylmethionine Decarboxylase 1) affects the p-cresol content by regulating the polyamine pathway, affecting the unique flavor of GD. This study revealed the unique flavor composition of GD, analyzed the advantages of species hybridization, and thus, provides a new direction and theoretical basis for pork quality improvement.

Exogenous Hemin alleviated cadmium stress in maize (Zea mays L.) by enhancing leaf photosynthesis, AsA-GSH cycle and polyamine metabolism.

Cadmium (Cd) stress is one of the principal abiotic stresses that inhibit maize growth. The research was to explore (hemin chloride) Hemin (100 μmol L−1) on photosynthesis, ascorbic acid (AsA)-glutathione (GSH) cycle system, and polyamine metabolism of maize under Cd stress (85 mg L−1) using nutrient solution hydroponics, with Tiannong 9 (Cd tolerant) and Fenghe 6 (Cd sensitive) as experimental materials. The results showed that Hemin can increase leaf photosynthetic pigment content and ameliorate the ratio of Chlorophyll a/chlorophyll b (Chla/Chlb) under Cd stress. The values of ribose 1, 5-diphosphate carboxylase/oxygenase (RuBPcase) and phosphoenolpyruvate carboxylase (PEPCase), and total xanthophyll cycle pool [(violoxanthin (V), antiflavin (A) and zeaxanthin (Z)] increased, which enhancing xanthophyll cycle (DEPS) de-epoxidation, and alleviating stomatal and non-stomatal limitation of leaf photosynthesis. Hemin significantly increased net photosynthetic rate (Pn), stomatal conductance (gs), transpiration rate (Tr), photochemical quenching coefficient (qP), PSII maximum photochemical efficiency (Fv/Fm), and electron transfer rate (ETR), which contributed to the improvement of the PSII photosynthetic system. Compared with Cd stress, Hemin can reduce thiobartolic acid reactant (TBARS) content, superoxide anion radical (O2−) production rate, hydrogen peroxide (H2O2) accumulation, and the extent of electrolyte leakage (EL); decreased the level of malondialdehyde (MDA) content and increased the activities of superoxide dismutase (SOD), peroxidase (POD) and catalase (CAT); slowed the decrease in dehydroascorbic acid reductase (DHAR) and monodehydroascorbate reductase (MDHAR) activity and the increase in glutathione reductase (GR) and ascorbate peroxidase (APX) activity in leaves; promoted the increase in AsA and GSH content, decreased dehydroascorbic acid (DHA) and oxidized glutathione (GSSG), and increased AsA/DHA and GSH/GSSG ratios under Cd stress. Hemin promoted the increase of conjugated and bound polyamine content, and the conversion process speed of free putrescine (Put) to free spermine (Spm) and spermidine (Spd) in maize; decreased polyamine oxidase (PAO) activity and increased diamine oxidase (DAO), arginine decarboxylase (ADC), ornithine decarboxylase (ODC) and S-adenosylmethionine decarboxylase (SAMDC) enzyme activities in leaves under Cd stress.

Unraveling the genetics of polyamine metabolism in barley for senescence-related crop improvement

We explored the polyamine (PA) metabolic pathway genes in barley (Hv) to understand plant development and stress adaptation in Gramineae crops with emphasis on leaf senescence. Bioinformatics and functional genomics tools were utilized for genome-wide identification, comprehensive gene features, evolution, development and stress effects on the expression of the polyamine metabolic pathway gene families (PMGs). Three S-adenosylmethionine decarboxylases (HvSAMDCs), two ornithine decarboxylases (HvODCs), one arginine decarboxylase (HvADC), one spermidine synthase (HvSPDS), two spermine synthases (HvSPMSs), five copper amine oxidases (HvCuAOs) and seven polyamine oxidases (HvPAOs) members of PMGs were identified and characterized in barley. All the HvPMG genes were found to be distributed on all chromosomes of barley. The phylogenetic and comparative assessment revealed that PA metabolic pathway is highly conserved in plants and the prediction of nine H. vulgare miRNAs (hvu-miR) target sites, 18 protein-protein interactions and 961 putative CREs in the promoter region were discerned. Gene expression of HvSAMDC3, HvCuAO7, HvPAO4 and HvSPMS1 was apparent at every developmental stage. SPDS/SPMS gene family was found to be the most responsive to induced leaf senescence. This study provides a reference for the functional investigation of the molecular mechanism(s) that regulate polyamine metabolism in plants as a tool for future breeding decision management systems.

Polyamines in plasma membrane function in melatonin-mediated tolerance of apricot fruit to chilling stress

Polyamines are closely associated with environmental stresses and melatonin pretreatment enhances the resistance of fruit to chilling stress. However, a mechanism underlying melatonin-mediated chilling resistance remains to be answered. This research aimed to illuminate whether polyamines would be involved in melatonin-mediated chilling resistance. Therefore, in the experiment, the polyamines conjugated to the plasma membrane from the melatonin-pretreated apricot flesh cell were examined under chilling stress. Chilling resistance was judged by four parameters: fruit browning degree, plasma membrane permeability, malondialdehyde content and plasma membrane protein sulfhydryl level. Results showed melatonin pretreatment led to obvious rises in the levels of non-covalently conjugated spermine and spermidine, and covalently conjugated putrescine and spermidine in the plasma membrane. Methylglyoxyl-bis (guanylhydrazone) pretreatment could inhibit the melatonin-induced increases of non-covalently conjugated spermidine and spermine by inhibiting S-adenosylmethionine decarboxylase (SAMDC) activity and free spermidine and spermine contents in flesh, coupled with the decrease in chilling resistance. Similarly, phenanthroline pretreatment could inhibit the melatonin-induced increases in covalently conjugated putrescine and spermidine in the plasma membrane through inhibiting transglutaminase (TGase) activity and simultaneously could aggravate chilling damage. The results suggested melatonin pretreatment could enhance chilling resistance by increasing non-covalently conjugated spermidine and spermine, as well as covalently conjugated putrescine and spermidine in the plasma membrane of apricot fruit.

Exogenous spermidine regulates the anaerobic enzyme system through hormone concentrations and related-gene expression in Phyllostachys praecox roots under flooding stress

PurposeAcclimation to hypoxia and anoxia is important in various ecological systems, especially flooded soil. Phyllostachys pracecox is sensitive to flooding, and therefore, it is important to explore ways of alleviating hypoxia stress in the roots. In this study, we investigated the regulatory effect of spermidine (Spd) on flooded P. praecox seedlings. MethodsA batch experiment was carried out in roots treated with Spd under flooding for eight days. The following factors were subsequently measured: growth, survival rate, root respiratory activity, soluble protein and anaerobic respiration enzyme contents (pyruvate decarboxylase, PDC; alcohol dehydrogenase, ADH; lactate dehydrogenase, LDH; alanine aminotransferase, AlaAT), S-adenosylmethionine decarboxylase (SAMDC), nitrate reductase (NR), ACC oxidase (ACO) and ACC synthetase (ACS) activities, free Spd, spermine (Spm) and the diamine precursor putrescine (Put) content, indole-3-acetic acid (IAA) and abscisic acid (ABA) content, ethylene emissions and expression of hormone-related genes. ResultsApplication of Spd promoted root growth (root length, volume, surface and dry weight) and root respiratory inhibition, improved the soluble protein content, and reduced the O2·- production rate, H2O2 and MDA content to alleviate the damage of roots under flooding. A significant increase in SAMDC activity, and ABA and IAA contents were also observed, along with a reduction in ethylene emissions, NR, ACO and ACS activities (p < 0.05). Exogenous Spd increased the free Spd and Spm contents in the P. praecox roots, but decreased the free Put content. Taken together, these findings suggest that hypoxia stress was alleviated. Moreover, exogenous Spd up-regulated the expression of auxin-related genes ARF1, AUX1, AUX2, AUX3 and AUX4, and down-regulated the expression of ethylene-related ACO and ACS genes during flooding. In addition, correlation and RDA analysis showed that ARF1, ACO and ACS significantly promoted the expression of auxin, ACO and ACS enzyme activities, respectively (p < 0.05), while ADH, NR, AlaAT, ethylene emissions, Put, Spd, ACS and ACO were significantly correlated with ACS, ACO, and auxin-related gene expression (p < 0.05). Overall, ethylene emissions, ACS and ACO were identified as the main drivers of ethylene and auxin-related gene structure. ConclusionsThese results suggest that Spd regulated hormone concentrations, the content of Spd, Spm and Put, and related gene expression, in turn regulating physiological changes such as anaerobic enzyme activity, mitigating flooding stress in the roots and improving overall growth. Spd therefore has the potential to improve the adaptability of P. praecox to flooding stress.

Improvement of cold tolerance in maize (Zea mays L.) using Agrobacterium-mediated transformation of ZmSAMDC gene

ABSTRACT Maize (Zea mays L.) is a food crop sensitive to low temperatures. As one of the abiotic stress hazards, low temperatures seriously affect the yield of maize. However, the genetic basis of low-temperature adaptation in maize is still poorly understood. In this study, maize S-adenosylmethionine decarboxylase (SAMDC) was localized to the nucleus. We used Agrobacterium-mediated transformation technology to introduce the SAMDC gene into an excellent maize inbred line variety GSH9901 and produced a cold-tolerant transgenic maize line. After three years of single-field experiments, the contents of polyamines (PAs), proline (Pro), malondialdehyde (MDA), antioxidant enzymes and ascorbate peroxidases (APXs) in the leaves of the transgenic maize plants overexpressing the SAMDC gene significantly increased, and the expression of elevated CBF and cold-responsive genes effectively increased. The agronomic traits of the maize overexpressing the SAMDC gene changed, and the yield traits significantly improved. However, no significant changes were found in plant height, ear length, and shaft thickness. Therefore, SAMDC enzymes can effectively improve the cold tolerance of maize.

Abstract 5488: The potential of spermine analogue SBP-101 (diethyl dihydroxyhomospermine) as a polyamine metabolism modulator in ovarian cancer

Abstract The naturally occurring polyamines, putrescine, spermidine and spermine, are polycationic alkylamines that are essential for cellular growth and proliferation. As such, many cancers are reliant on elevated polyamine levels that are maintained through dysregulated polyamine metabolism. Polyamine metabolism is thus a promising target for cancer therapeutics, and modulation of polyamine metabolism has been attempted with numerous enzyme inhibitors and polyamine analogues. SBP-101 (diethyl dihydroxyhomospermine) is a novel spermine analogue that has shown efficacy in slowing pancreatic tumor progression both in vitro and in vivo. Here we determined the effect of SBP-101 treatment on polyamine metabolism in a variety of cancer cell types in vitro including lung, ovarian, prostate, pancreatic and breast. We evaluated the activity of four enzymes involved in the polyamine pathway following treatment with either SBP-101 or the well-characterized spermine analogue, BENSpm (N1,N11-bisethylnorspermine). Additionally, we determined by high performance liquid chromatography the effect of SBP-101 on intracellular polyamine pools and the accumulation of the analogue itself. The activity of the biosynthetic enzymes ornithine decarboxylase (ODC) and S-adenosylmethionine decarboxylase and the catabolic enzymes spermidine/spermine-N-(1)-acetyltransferase and spermine oxidase were determined with and without treatment with the polyamine analogues. SBP-101 treatment resulted in a varying increase in the activity of polyamine catabolic enzymes in a subset of tested cell lines, while it downregulated the activity of the biosynthetic enzyme ODC across all cell types studied. These results indicate that SBP-101 likely exerts its effect predominately through decreased polyamine biosynthesis with minor upregulation of catabolism in contrast to the structurally similar BENSpm where the increase in polyamine catabolism is the predominant response. A sustained elevation of polyamine levels plays a role in the immunosuppressive environment of some cold tumors, and the pharmacologic and genetic modulation of polyamine metabolism has demonstrated success in reducing immunosuppressive phenotypes. Therefore, to extend our in vitro results, we evaluated the efficacy of SBP-101 in the immunosuppressive VDID8+ murine ovarian cancer model. SBP-101 caused a marked increase in median survival comparable to that of some promising combination therapies. Future studies will determine the synergistic effects, if any, of SBP-101 in combination with other polyamine metabolism modulators as well as with immune modulators. Citation Format: Cassandra E. Holbert, Tracy Murray Stewart, Jennifer K. Simpson, Michael J. Walker, Robert A. Casero. The potential of spermine analogue SBP-101 (diethyl dihydroxyhomospermine) as a polyamine metabolism modulator in ovarian cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5488.

Polyamine synthesis enzyme AMD1 is closely related to the tumorigenesis and prognosis of human breast cancer

Adenosylmethionine decarboxylase 1 (AMD1) has been implicated in carcinogenesis and tumor progression. However, the potential biomechanism and biological implications of AMD1 in breast cancer (BC) remain unclear. The purpose of this study was to investigate the effect of abnormal expression of AMD1 in BC. The expression of AMD1 in different human BC cell lines was studied by using western blotting and qRT–PCR. In vitro cell proliferation, clone formation, cell cycle and apoptosis assays were performed to explore the effect of AMD1 on cellular proliferation. Xenograft mouse models were established to elucidate the role of AMD1 in BC growth. The expression profiles of AMD1 in 28 pairs of BC tissues and adjacent noncancerous tissues (ANTs) were investigated by using western blotting and immunohistochemistry. The clinical implication and prognostic evaluation of AMD1 in BC were examined by excavating the online database. We found that the expression levels of AMD1 in BC cell lines were significantly higher than those in the normal human breast epithelial cell line MCF-10A. In addition, AMD1 potentiated proliferation, induced cell cycle progression and inhibited apoptosis in BC cells. Subcutaneous tumor xenografts also supported the promotive role of AMD1 in BC growth. We discovered that the level of AMD1 in BC tissues was significantly higher than that in ANTs. Using the online database, increased AMD1 was found to be associated with clinical indicators and predicted a poor prognosis in patients with BC. Our findings indicate that AMD1 elicits potent oncogenic effects on the malignant progression of BC. AMD1 might serve as a promising diagnostic biomarker and therapeutic target for patients with BC.

CO2 Enrichment Differentially Upregulated Sugar, Proline, and Polyamine Metabolism in Young and Old Leaves of Wheat and Sorghum to Mitigate Indium Oxide Nanoparticles Toxicity.

Soil contamination with indium oxide nanoparticles (In2O3-NPs) is a challenge for plant growth and productivity. Despite In2O3-NPs toxicity, their effects on plant growth and metabolism are largely unknown, particularly under future climate CO2 (eCO2). Therefore, the In2O3-NPs toxicity and stress mitigating impact of eCO2 in the young and old leaves of C3 (wheat) and C4 (sorghum) plants were investigated. Overall, In2O3-NPs significantly retard the biomass and photosynthetic machinery of all tested crops, particularly the young leaves of C3 plants. Consequently, In2O3-NPs altered C and N metabolism in C3 and C4 plants. On the other hand, eCO2 contrarily alleviated the hazardous effects of In2O3-NPs on growth and photosynthesis, especially in the young leaves of C4 plants. Increased photosynthesis consequently enhanced the soluble sugars’ accumulation and metabolism (e.g., sucrose P synthase, cytosolic, and vacuolar invertase) in all stressed plants, but to a greater extent in C4 young leaves. High sugar availability also induced TCA organic and fatty acids’ accumulation. This also provided a route for amino acids and polyamines biosynthesis, where a clear increase in proline biosynthetic enzymes [e.g., pyrroline-5-carboxylate synthetase (P5CS), ornithine aminotransferase (OAT), Pyrroline-5-carboxylate reductase (P5CR), pyrroline-5-carboxylate dehydrogenase (P5CDH), and proline dehydrogenase (PRODH)] and polyamine metabolic enzymes (e.g., spermine and spermidine synthases, ornithine decarboxylase, and adenosyl methionine decarboxylase) were mainly recorded in C4 young leaves. The observed increases in these metabolites involved in osmo- and redox-regulation to reduce In2O3-NPs induced oxidative damage. Overall, our study, for the first time, shed light on how eCO2 differentially mitigated In2O3-NPs stress in old and young leaves of different species groups under the threat of In2O3-NPs contamination.

Polyamine Metabolism in Leishmania Parasites: A Promising Therapeutic Target.

Parasites of the genus Leishmania cause a variety of devastating and often fatal diseases in humans and domestic animals worldwide. The need for new therapeutic strategies is urgent because no vaccine is available, and treatment options are limited due to a lack of specificity and the emergence of drug resistance. Polyamines are metabolites that play a central role in rapidly proliferating cells, and recent studies have highlighted their critical nature in Leishmania. Numerous studies using a variety of inhibitors as well as gene deletion mutants have elucidated the pathway and routes of transport, revealing unique aspects of polyamine metabolism in Leishmania parasites. These studies have also shed light on the significance of polyamines for parasite proliferation, infectivity, and host–parasite interactions. This comprehensive review article focuses on the main polyamine biosynthetic enzymes: ornithine decarboxylase, S-adenosylmethionine decarboxylase, and spermidine synthase, and it emphasizes recent discoveries that advance these enzymes as potential therapeutic targets against Leishmania parasites.

Exogenously applied spermidine alleviates hypoxia stress in Phyllostachys praecox seedlings via changes in endogenous hormones and gene expression

BackgroundHypoxia stress is thought to be one of the major abiotic stresses that inhibits the growth and development of higher plants. Phyllostachys pracecox is sensitive to oxygen and suffers soil hypoxia during cultivation; however, the corresponding solutions to mitigate this stress are still limited in practice. In this study, Spermidine (Spd) was tested for regulating the growth of P. praecox seedlings under the hypoxia stress with flooding.ResultsA batch experiment was carried out in seedlings treated with 1 mM and 2 mM Spd under flooding for eight days. Application of 1 mM and 2 mM Spd could alleviate plant growth inhibition and reduce oxidative damage from hypoxia stress. Exogenous Spd significantly (P < 0.05) increased proline, soluble protein content, catalase (CAT), superoxide dismutase (SOD), and S-adenosylmethionine decarboxylase (SAMDC) activity, enhanced abscisic acid (ABA) and indole-3-acetic acid (IAA) content, and reduced ethylene emission, hydrogen peroxide (H2O2), superoxide radical (O2·−) production rate, ACC oxidase (ACO) and ACC synthase (ACS) to protect membranes from lipid peroxidation under flooding. Moreover, exogenous Spd up-regulated the expression of auxin-related genes auxin responsive factor1 (ARF1), auxin1 protein (AUX1), auxin2 protein (AUX2), auxin3 protein (AUX3) and auxin4 protein (AUX4), and down-regulated the expression of ethylene-related ACO and ACS genes during flooding.ConclusionThe results indicated that exogenous Spd altered hormone concentrations and the expression of hormone-related genes, thereby protecting the bamboo growth under flooding. Our data suggest that Spd can be used to reduce hypoxia-induced cell damage and improve the adaptability of P. praecox to flooding stress.

Correction to: Impact of S-Adenosylmethionine Decarboxylase 1 on Pulmonary Vascular Remodeling.

Correction to: Impact of S-Adenosylmethionine Decarboxylase 1 on Pulmonary Vascular Remodeling.