Spermidine Levels Research Articles

Calcium combined with vacuum treatment improves postharvest storage quality of Agaricus bisporus by regulating polyamine metabolism

Calcium (Ca) immersion treatment has been used for the preservation of Agaricus bisporus (A. bisporus), but the effective dosage of Ca absorption has often been disregarded. In our study, vacuum pretreatment was performed to promote Ca infiltration in A. bisporus. Vacuum pretreatment (−0.1 MPa, 5 min, Vac + Ca group) exhibited a super effectiveness in promoting Ca absorption. The results of Ca diffusion simulation using COMSOL Multiphysics showed that Ca level in the center of the sample in the Vac + Ca group increased from 0.1020 to 0.2028 g kg−1 during a period of 0 to 60 min. Additionally, the effects of Vac + Ca treatment on the polyamine (PA) metabolism during a 3-day room temperature storage of A. bisporus were investigated. Vac + Ca treatment resulted in a reduction of putrescine (Put) level and an elevation in spermidine (Spd) level, suggesting that the treatment may facilitate the conversion of Put to Spd. Interestingly, a negative linear correlation between changes in Spd level and both the browning index and weight loss, while a positive correlation was found with alterations in hardness were observed. Moreover, several amino acids and enzymes involved in PA metabolism, including arginine, methionine, ornithine decarboxylase, arginase, S-adenosylmethionine decarboxylase, and spermidine synthase, were also affected by this treatment. Therefore, the increase in Spd induced by Vac + Ca treatment may be one of the underlying mechanisms responsible for extending the postharvest lifespan of A. bisporus.

Plasma levels of urea cycle related amino acids in association with risk of ischemic stroke: Findings from a nested case-control study

ObjectivesThe role of urea cycle related amino acids in the development of ischemic stroke (IS) remains unclear. The study aimed to evaluate the association of these amino acids with IS. Materials and MethodsWe conducted a case-control study nested within a cohort study in Changshu, Eastern China. A total of 321 cases and 321 controls matched by age and gender were finally included. Plasma levels of ornithine, arginine, spermidine, and proline were measured using ultra-high performance liquid chromatography–tandem mass-spectrometry (UHPLC–MS/MS). Odds ratios (ORs) and their 95 % confidence intervals (CIs) were calculated by conditional logistic regression analyses. ResultsPlasma ornithine was inversely associated with risk of IS [crude OR: 0.62 (95 % CI: 0.40-0.97)]. After adjustment for body mass index, smoking, hypertension, family history of stroke, estimated glomerular filtration rate, and total cholesterol, the corresponding ORs for the highest compared to the lowest quartiles was essentially unchanged [adjusted OR: 0.62 (95 % CI: 0.39-0.99)]. The risk association remained significant after repeating the analyses by excluding the first two years of follow-up. Plasma arginine, spermidine, and proline were not associated with the risk of IS. ConclusionWe observed that higher plasma levels of ornithine were associated with a lower risk of incident IS. Our novel findings suggest a protective role of ornithine in the pathogenesis of IS.

An Integrative Multi‐Omics Approach Reveals Molecular Signatures Associated with Age and High‐Fat Diet in Mouse Models of Alzheimer’s Disease

AbstractBackgroundAlzheimer’s disease (AD) is a complex, multifactorial pathology with high heterogeneity in biological alterations. Our understanding of cellular and molecular mechanisms from disease risk variants to various phenotypes is still limited. Therefore, it is required to integrate the information from multiple data modalities for thorough exploration of endophenotype networks, biological interactions related to disease and thus accelerate our understanding of heterogeneity in Alzheimer’s disease.MethodIn this study, we performed multi‐level omics in a cohort of mouse models expressing humanized Abeta and two genetic risk factors (APOE4 and Trem2*R47H) at multiple ages for both sexes. Data from multiple omics platforms (transcriptomics, proteomics, and metabolomics) were analyzed at single‐omic level as well as integrated in an unbiased fashion, considering interaction between modalities using multi‐omics factor analysis (MOFA). We also systematically aligned multimodal mouse data to relevant human studies cohort.ResultMulti‐omics integration identified major components of heterogeneity explaining the variance within the cohort and differentially associated with age, sex, and high fat diet. Enrichment analysis of genes and protein associated with these components were significantly enriched for multiple AD‐related processes. Specifically, components associated with age and diet related heterogeneity exhibited overrepresentation of immune response and metabolic processes as well as increased levels of long‐chain acylcarnitine’s and reduced levels of spermidine in aged and high‐fat diet fed AD mouse models, similar to human AD. In addition, we observed weak correspondence between change in protein and RNA expression in mouse models compared to controls, similar to recent results from the ROSMAP cohort, which reported weak correlation between protein and RNA expression. We also identified a negative correlation for the change in RNA expression between male and female mice.ConclusionWe identified axes of variation within a cohort of LOAD mouse models using integrative multi‐omics approach. Our analysis revealed multiple interaction between distinct multi‐omics molecular signatures associated with Alzheimer’s disease. We determined that mRNA profiling alone provides an incomplete picture of molecular mechanism of AD. In this study, we highlighted that assembling multi‐omics measurements reveal interrelated pathway alterations in AD and the ability to identify biomarkers combinations that may inform clinical practice.

Effects of Methionine Restriction from Different Sources on Sperm Quality in Aging Mice.

Decreased sperm quality causing poor pregnancy outcomes in aging males is a common problem. The aim of this study was to investigate the ameliorative effect of methionine restriction on sperm quality in aging mice, using methionine or 2-hydroxy-4-(methylthio)butanoate (HMTBA) as the methionine source, with a view to providing nutritional strategies to mitigate the decline in sperm quality in aging livestock. Fifty-one 6-week-old male mice were randomly divided into four groups: the non-aging group (NA, 0.86% methionine), the control diet group (CD, 0.86% methionine), the methionine-restricted group (MR, 0.17% methionine) and the HMTBA-restricted group (HR, 0.17% methionine). The mice in the CD, MR and HR groups were injected with a daily dose of 0.25 mL/20 g body weight of 10% D-galactose to establish an aging model. The test period was 42 days. The results showed that aging mice in the CD group had impaired testicular morphology and significantly decreased sperm quality compared to those in the NA group. Aging mice in the MR and HR groups showed attenuated impaired testicular morphology and improved sperm quality, especially sperm acrosomal integrity and membrane integrity, compared to mice in the CD group. In addition, mice in the MR and HR groups had reduced testicular inflammation and oxidative stress, increased spermidine levels, and reduced sperm RNA N6-methyladenosine (m6A) and DNA 5-methylcytosine (5mC) levels. Spermidine levels were positively correlated, whereas sperm RNA m6A and DNA 5mC levels were negatively correlated with sperm quality parameters. Our study suggests that methionine restriction alleviates the decline in sperm quality in aging mice, which may be related to changes in methionine metabolism and inhibition of sperm DNA and RNA methylation.

Dendrobium huoshanense Polysaccharide Improves High-Fat Diet Induced Liver Injury by Regulating the Gut-Liver Axis.

Dendrobium huoshanense is an important Traditional Chinese medicine that thickens the stomach and intestines. Its active ingredient Dendrobium huoshanense polysaccharide (DHP), was revealed to relieve the symptoms of liver injury. However, its mechanism of action remains poorly understood. This study aimed to investigate the mechanism of DHP in protecting the liver. The effects of DHP on lipid levels, liver function, and intestinal barrier function were investigated in mice with high-fat diet-induced liver damage. Changes in the gut flora and their metabolites were analyzed using 16S rRNA sequencing and metabolomics. The results showed that DHP reduced lipid levels, liver injury, and intestinal permeability. DHP altered the intestinal flora structure and increased the relative abundance of Bifidobacterium animalis and Clostridium disporicum. Furthermore, fecal metabolomics revealed that DHP altered fecal metabolites and significantly increased levels of gut-derived metabolites, spermidine, and indole, which have been reported to inhibit liver injury and improve lipid metabolism and the intestinal barrier. Correlation analysis showed that spermidine and indole levels were significantly negatively correlated with liver injury-related parameters and positively correlated with the intestinal species B. animalis enriched by DHP. Overall, this study confirmed that DHP prevented liver injury by regulating intestinal microbiota dysbiosis and fecal metabolites.

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

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.

Physiological and Biochemical Parameters of Field Bean (Vicia faba var. minor) Seeds Stored for 33 Years

Changes occurring in seeds of two field bean cultivars during long-term storage at −14 °C, +4 °C and +20 °C were examined. It was found that after 33 years of storage at low temperatures, the seeds showed a significant decline in biological quality, and the seeds stored at +20 °C completely lost their germination capacity. As the seeds aged, changes in their phenolic composition, concentrations of polyamines and activity of enzymes associated with redox homeostasis and phenolic metabolism could be easily observed. The activity of ascorbate peroxidase and phenylalanine ammonia-lyase in deteriorated seeds was higher than in high-quality seeds. The activity of guaiacol peroxidase, catalase and glutathione reductase in low-quality seeds was decreased. With superoxide dismutase, the pattern was less clear-cut and depended on both seed biological quality and cultivar. Whole seed levels of spermine and spermidine decreased in ageing seeds and were lowest in non-germinating seeds. However, the opposite pattern was observed regarding spermine and spermidine, as well as putrescine, in seed coats. The obtained results indicate that changes in the activity of redox and protective systems in seeds have a clear relationship with the seed biological quality and can be detected even at a moderate level of seed deterioration. The analyses of such changes can significantly facilitate the assessment of seed quality and can therefore be of interest for seed companies and seed banks.

Polyamine metabolite spermidine rejuvenates oocyte quality by enhancing mitophagy during female reproductive aging.

Advanced age is a primary risk factor for female infertility due to reduced ovarian reserve and declining oocyte quality. However, as an important contributing factor, the role of metabolic regulation during reproductive aging is poorly understood. Here, we applied untargeted metabolomics to identify spermidine as a critical metabolite in ovaries to protect oocytes against aging. In particular, we found that the spermidine level was reduced in ovaries of aged mice and that supplementation with spermidine promoted follicle development, oocyte maturation, early embryonic development and female fertility of aged mice. By microtranscriptomic analysis, we further discovered that spermidine-induced recovery of oocyte quality was mediated by enhancement of mitophagy activity and mitochondrial function in aged mice, and this mechanism of action was conserved in porcine oocytes under oxidative stress. Altogether, our findings suggest that spermidine supplementation could represent a therapeutic strategy to ameliorate oocyte quality and reproductive outcome in cis-gender women and other persons trying to conceive at an advanced age. Future work is needed to test whether this approach can be safely and effectively translated to humans.

Inhibition of Polyamine Catabolism Reduces Cellular Senescence.

The aging of the global population has necessitated the identification of effective anti-aging technologies based on scientific evidence. Polyamines (putrescine, spermidine, and spermine) are essential for cell growth and function. Age-related reductions in polyamine levels have been shown to be associated with reduced cognitive and physical functions. We have previously found that the expression of spermine oxidase (SMOX) increases with age; however, the relationship between SMOX expression and cellular senescence remains unclear. Therefore, we investigated the relationship between increased SMOX expression and cellular senescence using human-liver-derived HepG2 cells. Intracellular spermine levels decreased and spermidine levels increased with the serial passaging of cells (aged cells), and aged cells showed increased expression of SMOX. The levels of acrolein-conjugated protein, which is produced during spermine degradation, also increases. Senescence-associated β-gal activity was increased in aged cells, and the increase was suppressed by MDL72527, an inhibitor of acetylpolyamine oxidase (AcPAO) and SMOX, both of which are enzymes that catalyze polyamine degradation. DNA damage accumulated in aged cells and MDL72527 reduced DNA damage. These results suggest that the SMOX-mediated degradation of spermine plays an important role in cellular senescence. Our results demonstrate that cellular senescence can be controlled by inhibiting spermine degradation using a polyamine-catabolizing enzyme inhibitor.

Reduced iron and cobalt levels in response to curcumin supplementation are not responsible for the prolonged larval development and do not affect the oxidative stress tolerance and polyamine status of D. melanogaster.

Recent reports indicated that the phytochemical curcumin possesses iron-chelating activity. Here, by employing the fruit fly Drosophila melanogaster, we conducted feeding studies supplementing curcumin or, as a control, the iron chelator bathophenanthroline (BPA). First, the absorption and further metabolization of dietary curcuminoids were proved by metabolomics analyses. Next, we found that 0.2% dietary curcumin, similar to BPA, lowered the iron but also the cobalt content, and to a lesser extent affected the manganese and zinc status. Supplementation during larval stages was required and sufficient for both compounds to elicit these alterations in adult animals. However, curcumin-induced retarded larval development was not attributable to the changed trace metal status. In addition, a reduction in the iron content of up to 70% by curcumin or BPA supplementation did not reduce heme-dependent catalase activity and tolerance toward H2 O2 in D. melanogaster. Moreover, polyamines were not influenced by curcumin treatment and decreased iron levels. This was confirmed for selected organs from 0.2% curcumin-treated mice, except for the spleen. Here, elevated spermidine level and concomitant upregulation of genes involved in polyamine production were associated with a putatively anemia-derived increased spleen mass. Our data underline that the metal-chelating property of curcumin needs to be considered in feeding studies.

Association of spermidine blood levels with microstructure of sleep—implications from a population-based study

Deteriorations in slow wave sleep (SWS) have been linked to brain aging and Alzheimer’s disease (AD), possibly due to its key role in clearance of amyloid-beta and tau (Aß/tau), two pathogenic hallmarks of AD. Spermidine administration has been shown to improve sleep quality in animal models. So far, the association between spermidine levels in humans and parameters of SWS physiology are unknown but may be valuable for therapeutic strategies. Data from 216 participants (age range 50–81 years) of the population-based Study of Health in Pomerania TREND were included in our analysis. We investigated associations between spermidine plasma levels, key parameters of sleep macroarchitecture and microarchitecture that were previously associated with AD pathology, and brain health measured via a marker of structural brain atrophy (AD score). Higher spermidine levels were significantly associated with lower coupling between slow oscillations and spindle activity. No association was evident for SWS, slow oscillatory, and spindle activity throughout non-rapid eye movement sleep. Furthermore, elevated spermidine blood levels were significantly associated with a higher AD score, while sleep markers revealed no association with AD score. The association between higher spermidine levels and brain health was not mediated by coupling between slow oscillations and spindle activity. We report that higher spermidine blood levels are associated not only with deteriorated brain health but also with less advantageous markers of sleep quality in older adults. Future studies need to evaluate whether sleep, spermidine, and Aß/tau deposition are interrelated and whether sleep may play a mediating role.

Correlation analysis of polyamine metabolism and reproductive hormone levels in goose ovarian follicles

To investigate the relationship between polyamine metabolism and reproductive hormones in ovarian follicles of Sichuan white geese, follicle polyamine content and reproductive hormone levels and gene expressions related to polyamine metabolism, steroidogenesis and steroid hormone receptors were detected by HPLC, ELISA and RT-qPCR. The results showed that the overall trend of spermidine and spermine levels increased first and then decreased as increasing follicle size, with the highest level in F3 and F5 follicles (P < 0.05). Putrescine and 17β-estradiol (E2) levels in hierarchical follicles were significantly lower than those in prehierarchical follicles (P < 0.05). Progesterone (P4) first increased and then decreased, with the highest level in the F5 follicle (P < 0.05). The expression levels of estrogen receptor 1 (ER1) showed an overall increase as increasing follicle size (except in F3 follicles), while estrogen receptor 2 (ER2) in hierarchical follicles was significantly lower than that in the prehierarchical follicles (P < 0.05). In addition, the overall expression level of progesterone receptor (PR) decreased, with no significant differences among F1, F2 and F3 follicles (P > 0.05). Yolk putrescine contents were positively correlated with yolk E2 concentrations and PR expression levels (P < 0.05), A significant positive correlation of spermidine levels with yolk P4 concentrations and PR expressions was also observed, as well as the spermine levels with yolk P4 concentrations (P < 0.05). In summary, polyamines were involved in the regulation of follicular development in geese, and this regulation played a role in affecting steroidogenesis and the expression of genes related to hormone receptors.

Dynamics of Polyamines, Proline, and Ethylene Metabolism under Increasing Cold in Winter Oilseed Rape.

Cold stress is among the most important environmental factors reducing the yield of crops. The present study aimed to investigate the impact of increasing cold stress conditions on winter oilseed rape polyamines, proline, and ethylene metabolism in acclimated and non-acclimated winter oilseed rape. This study was carried out under controlled conditions in the laboratory. The winter oilseed rape hybrid 'Visby' was used in the experiment. Acclimated and non-acclimated plants were subjected to a two-day-long increasing cold (from -1 °C to -3 °C) treatment. HPTLC, RT-qPCR, spectral analysis, and gas chromatography methods were used to analyse the levels of polyamines, gene expression, proline, and ethylene, respectively. This study showed a decrease in putrescine, spermidine, and spermine content during cold acclimation and a decrease in putrescine and spermidine levels at sub-zero temperatures. There were intensive changes in ADC2 gene expression, proline, and ethylene levels in non-acclimated plants: a substantial increase after exposure to -1 °C temperature and a sharp decrease after exposure to -3 °C temperature. The changes in these parameters were lower or absent in acclimated plants. The phenomena observed in this study add new insights to the knowledge about the plant stress response and suggest questions to be answered in the future.

Evaluating biogenic amines and pH levels in farmed rainbow trout (Oncorhynchus mykiss) for freshness assessment during storage

This study examined the production of eight key biogenic amines (methylamine, tryptamine, putrescine, cadaverine, histamine, tyramine, spermidine, and spermine) in 120 samples of farmed rainbow trout during various storage conditions, and determined any accompanying variations in pH. The main objective of this study was to identify which of the eight biogenic amines could be used as chemical markers to evaluate the quality of farmed rainbow trout. Histamine and tryptamine were not present in any of the samples, and the levels of cadaverine were inconsistent. The levels of putrescine significantly increased at 0 °C (by day 9), 2 °C (by day 8), and 4 °C (by day 4). Tyramine, spermidine, and spermine levels exhibited fluctuations but had a significant positive correlation with the levels of putrescine. The pH levels slightly increased from their initial values across all storage temperatures, with no significant variations observed. Based on the results, it can be concluded that putrescine may serve as an effective marker of the freshness of farmed rainbow trout during storage.

Response to Cadmium Toxicity: Orchestration of Polyamines and microRNAs in Maize Plant.

Cadmium (Cd) is a heavy metal that is widely contaminating the environment due to its uses in industries as corrosive reagents, paints, batteries, etc. Cd can easily be absorbed through plant roots and may have serious negative impacts on plant growth. To investigate the mechanisms utilized by plants to cope with Cd toxicity, an experiment was conducted on maize seedlings. We observed that the plant growth and photosynthetic mechanism were negatively influenced during 20 days of Cd stress. The expression levels of ornithine decarboxylase (ORDC) increased in the six seedlings under Cd exposure compared to the control. However, Cd toxicity led to an increase in putrescine (Put) content only on day 15 when compared to the control plants. In fact, with the exception of day 15, the increases in the ORDC transcript levels did not show a direct correlation with the observed increases in Put content. Spermidine and Spermine levels were reduced on day 6 by Cd application, which was parallel with suppressed Spermidine synthase gene. However, an increase in Spermidine and Spermine levels was observed on day 12 along with a significant elevation in Spermidine synthase expression. On day 6, Cd was observed to start accumulating in the root with an increase in the expression of microRNA 528; while on day 15, Cd started to be observed in the shoot part with an increase in microRNA 390 and microRNA 168. These results imply that different miRNAs may regulate polyamines (PAs) in maize under Cd toxicity, suggesting a plant-derived strategy to commit a PAs/miRNA-regulated mechanism/s in different developmental stages (time points) in response to Cd exposure.

Alterations of the Gut Microbiota and Metabolomics Associated with the Different Growth Performances of Macrobrachium rosenbergii Families.

To investigate the key gut microbiota and metabolites associated with the growth performance of Macrobrachium rosenbergii families, 16S rRNA sequencing and LC-MS metabolomic methods were used. In this study, 90 M. rosenbergii families were bred to evaluate growth performance. After 92 days of culture, high (H), medium (M), and low (L) experimental groups representing three levels of growth performance, respectively, were collected according to the weight gain and specific growth rate of families. The composition of gut microbiota showed that the relative abundance of Firmicutes, Lachnospiraceae, Lactobacillus, and Blautia were much higher in Group H than those in M and L groups. Meanwhile, compared to the M and L groups, Group H had significantly higher levels of spermidine, adenosine, and creatinine, and lower levels of L-citrulline. Correlation analysis showed that the abundances of Lactobacillus and Blautia were positively correlated with the levels of alpha-ketoglutaric acid and L-arginine. The abundance of Blautia was also positively correlated with the levels of adenosine, taurine, and spermidine. Notably, lots of metabolites related to the metabolism and biosynthesis of arginine, taurine, hypotaurine, and fatty acid were upregulated in Group H. This study contributes to figuring out the landscape of the gut microbiota and metabolites associated with prawn growth performance and provides a basis for selective breeding.

Exogenous application of spermidine and methyl jasmonate can mitigate salt stress in fenugreek (Trigonella foenum-graecum L.)

Fenugreek (Trigonella foenum-graecum L.) has long been cultivated as both culinary and medicinal plant. The objective of this study was to investigate the effect of plant growth regulators such as spermidine (Spd) and methyl jasmonate (MeJA) on morpho-physiological and biochemical properties of fenugreek under saline conditions. A replicated greenhouse experiment in completely randomized block design was conducted with two levels of salinity (0.5 dS/m as control and 6 dS/m), three levels of spermidine (0, 1, 2 mM) and methyl jasmonate (0, 100, 200 µM), respectively. The results showed that salinity elevation reduced the leaf relative water content, leaf water potential, canopy-air temperature difference, photochemistry efficiency of photosystem II, and water-use efficiency of fenugreek. In contrast, salinity increased leaf thickness,greenness index, canopy temperature, leaf Na+, ash contents, malondialdehyde, other aldehydes, and electrolyte leakage. Moreover, Salinity stress reduced the amount of photosynthetic pigments, chlorophyll a/b ratio, total soluble protein, K+, maximum fluorescence, and K+/Na+ ratio in leaves. Elevation of water salinity, however, resulted in an increase in the activity of antioxidant enzymes (except superoxide dismutase), proline, and minimum fluorescence. When fenugreek was treated with 1 mM spermidine and/or 100 µM methyl jasmonate, the adverse effects of salinity stress were significantly mitigated, while the effects of these plant growth regulators on mitigating salinity stress were less pronounced at higher concentrations (2 mM spermidine and/or 200 µM methyl jasmonate). The current study suggests the application of 1 mM spermidine and/or 100 µM methyl jasmonate during the vegetative growth stage mitigating the adverse effects of salinity with an associated improvement in plant growth under moderate salinity (about 6 dS/m) when used for irrigation.

Arbuscular mycorrhizal fungi and endophytic fungi differentially modulate polyamines or proline of peach in response to soil flooding

Symbiotic fungi are involved in plant flooding tolerance, while the underlying mechanism is not yet known. Since polyamines and proline are also associated with stress tolerance, it is hypothesized that the enhancement of stress resistance by symbiotic fungi is associated with changes in polyamines (PAs) and/or proline. The aim of this study was to analyze the effect of inoculation with Funneliformis mosseae and Serendipita indica on growth, polyamine and its metabolism, and proline and its metabolism in peach (Prunus persica) under flooded conditions. Two-week flooding did not affect root colonization frequence of F. mosseae, while it promoted root colonization frequence of S. indica. Inoculated plants with F. mosseae and S. indica maintained relatively higher growth rates of peach under flooding than those of uninoculated plants. F. mosseae promoted root ornithine levels and arginine decarboxylase and ornithine decarboxylase activities under flooding, which promoted putrescine (Put), cadaverine (Cad) and spermidine (Spd) levels. Conversely, S. indica inhibited levels of arginine, ornithine, and agmatine and arginine decarboxylase activities, thus decreasing PAs under flooding. PAs were negatively correlated with expressions of polyamine uptake transporter 1 (PUT1) and PUT4 in peach. Transporters of polyamine (TPO) of F. mosseae and S. indica were regulated by flooding, of which FmTPO1 was positively correlated with Put, Cad, and Spd, along with a positive correlation of Spd with SiTPO1, SiTPO2, and SiTPO4. Under flooding, F. mosseae inhibited proline, while S. indica increased proline, correlated with Δ1-pyrroline-5-carboxylate synthetase 2 expressions. It thus was concluded that F. mosseae modulated polyamine accumulation while S. indica induced proline accumulation to tolerate flooding.

A Fine-Tuning of the Plant Hormones, Polyamines and Osmolytes by Ectomycorrhizal Fungi Enhances Drought Tolerance in Pedunculate Oak.

The drought sensitivity of the pedunculate oak (Quercus robur L.) poses a threat to its survival in light of climate change. Mycorrhizal fungi, which orchestrate biogeochemical cycles and particularly have an impact on the plant's defense mechanisms and metabolism of carbon, nitrogen, and phosphorus, are among the microbes that play a significant role in the mitigation of the effects of climate change on trees. The study's main objectives were to determine whether ectomycorrhizal (ECM) fungi alleviate the effects of drought stress in pedunculate oak and to investigate their priming properties. The effects of two levels of drought (mild and severe, corresponding to 60% and 30% of field capacity, respectively) on the biochemical response of pedunculate oak were examined in the presence and absence of ectomycorrhizal fungi. To examine whether the ectomycorrhizal fungi modulate the drought tolerance of pedunculate oak, levels of plant hormones and polyamines were quantified using UPLC-TQS and HPLC-FD techniques in addition to gas exchange measurements and the main osmolyte amounts (glycine betaine-GB and proline-PRO) which were determined spectrophotometrically. Droughts increased the accumulation of osmolytes, such as proline and glycine betaine, as well as higher polyamines (spermidine and spermine) levels and decreased putrescine levels in both, mycorrhized and non-mycorrhized oak seedlings. In addition to amplifying the response of oak to severe drought in terms of inducible proline and abscisic acid (ABA) levels, inoculation with ECM fungi significantly increased the constitutive levels of glycine betaine, spermine, and spermidine regardless of drought stress. This study found that compared to non-mycorrhized oak seedlings, unstressed ECM-inoculated oak seedlings had higher levels of salicylic (SA) and abscisic acid (ABA) but not jasmonic acid (JA), indicating a priming mechanism of ECM is conveyed via these plant hormones. According to a PCA analysis, the effect of drought was linked to the variability of parameters along the PC1 axe, such as osmolytes PRO, GB, polyamines, and plant hormones such as JA, JA-Ile, SAG, and SGE, whereas mycorrhization was more closely associated with the parameters gathered around the PC2 axe (SA, ODPA, ABA, and E). These findings highlight the beneficial function of the ectomycorrhizal fungi, in particular Scleroderma citrinum, in reducing the effects of drought stress in pedunculate oak.

Abstract 295: Targeting spermine synthase triggers lipid metabolism reprogramming as a new therapeutic option to combat colorectal cancer

Abstract Dysregulation of polyamine metabolism has been linked to the development of colorectal cancer (CRC). Our recent work demonstrates that spermine synthase (SMS), a polyamine biosynthetic enzyme that converts spermidine to spermine, is overexpressed in CRC, which is required for balancing cellular spermidine levels to facilitate CRC tumorigenesis (Nat Commun 11:3243, 2020). Our findings reveal SMS as an attractive therapeutic target in CRC; yet, genetic depletion of SMS expression only shows a limited antitumor effect. Using unbiased metabolomics and transcriptomics analyses, we identified a lipid metabolism reprograming as among the most impacted metabolic change by SMS depletion in CRC cells. Specifically, SMS depletion significantly altered long-chain fatty acid, triacylglycerol and phospholipid metabolism. Furthermore, targeted inhibition of SMS significantly increased the number of lipid droplets and the levels of long-chain fatty acid acylcarnitines for oxidative phosphorylation in mitochondria, and upregulated expression of genes associated with increased mobilization of polyunsaturated fatty acids and the genes associated with lipid peroxidation for induction of ferroptosis, an iron-dependent form of nonapoptotic cell death. The glutathione peroxidase 4 (GPX4) is a key negative regulator of ferroptosis by neutralizing lipid peroxides. Notably, pharmacological inhibition of GPX4 or its upstream regulator system xc − in combination with genetic depletion or pharmacologic inhibition of SMS synergistically caused lipid peroxidation leading to ferroptosis induction and marked suppression of CRC cell growth. Collectively, these findings highlight lipid metabolism reprograming as an adaptive response to targeted inhibition of SMS to enable CRC cell survival, which represents an Achilles’ heel that can be exploited for potential effective therapy for CRC. Citation Format: Murong Ma, Yubin Guo, Qing Ye, Pan Deng, Daheng He, Chi Wang, Qing-Bai She. Targeting spermine synthase triggers lipid metabolism reprogramming as a new therapeutic option to combat colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 295.