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1.
Male Fertility under Environmental Stress: Do Polyamines Act as Pollen Tube Growth Protectants?
Aloisi, I, Piccini, C, Cai, G, Del Duca, S
International journal of molecular sciences. 2022;(3)
Abstract
Although pollen structure and morphology evolved toward the optimization of stability and fertilization efficiency, its performance is affected by harsh environmental conditions, e.g., heat, cold, drought, pollutants, and other stressors. These phenomena are expected to increase in the coming years in relation to predicted environmental scenarios, contributing to a rapid increase in the interest of the scientific community in understanding the molecular and physiological responses implemented by male gametophyte to accomplish reproduction. Here, after a brief introduction summarizing the main events underlying pollen physiology with a focus on polyamine involvement in its development and germination, we review the main effects that environmental stresses can cause on pollen. We report the most relevant evidence in the literature underlying morphological, cytoskeletal, metabolic and signaling alterations involved in stress perception and response, focusing on the final stage of pollen life, i.e., from when it hydrates, to pollen tube growth and sperm cell transport, with these being the most sensitive to environmental changes. Finally, we hypothesize the molecular mechanisms through which polyamines, well-known molecules involved in plant development, stress response and adaptation, can exert a protective action against environmental stresses in pollen by decoding the essential steps and the intersection between polyamines and pollen tube growth mechanisms.
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2.
Arginase 2 and Polyamines in Human Pancreatic Beta Cells: Possible Role in the Pathogenesis of Type 2 Diabetes.
Marselli, L, Bosi, E, De Luca, C, Del Guerra, S, Tesi, M, Suleiman, M, Marchetti, P
International journal of molecular sciences. 2021;(22)
Abstract
Arginase 2 (ARG2) is a manganese metalloenzyme involved in several tissue specific processes, from physiology to pathophysiology. It is variably expressed in extra-hepatic tissues and is located in the mitochondria. In human pancreatic beta cells, ARG2 is downregulated in type 2 diabetes. The enzyme regulates the synthesis of polyamines, that are involved in pancreas development and regulation of beta cell function. Here, we discuss several features of ARG2 and polyamines, which can be relevant to the pathophysiology of type 2 diabetes.
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3.
Understanding the roles of osmolytes for acclimatizing plants to changing environment: a review of potential mechanism.
Ghosh, UK, Islam, MN, Siddiqui, MN, Khan, MAR
Plant signaling & behavior. 2021;(8):1913306
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Abstract
Abiotic stresses are significant environmental issues that restrict plant growth, productivity, and survival while also posing a threat to global food production and security. Plants produce compatible solutes known as osmolytes to adapt themselves in such changing environment. Osmolytes contribute to homeostasis maintenance, provide the driving gradient for water uptake, maintain cell turgor by osmotic adjustment, and redox metabolism to remove excess level of reactive oxygen species (ROS) and reestablish the cellular redox balance as well as protect cellular machinery from osmotic stress and oxidative damage. Perceiving the mechanisms how plants interpret environmental signals and transmit them to cellular machinery to activate adaptive responses is important for crop improvement programs to get stress-tolerant varieties. A large number of studies conducted in the last few decades have shown that osmolytes accumulate in plants and have strong associations with abiotic stress tolerance. Production of abundant osmolytes is needed for tolerance in many plant species. In addition, transgenic plants overexpressing genes for different osmolytes showed enhanced tolerance to various abiotic stresses. Many important aspects of their mechanisms of action are yet to be largely identified, especially regarding the relevance and relative contribution of specific osmolytes to the stress tolerance of a given species. Therefore, more efforts and resources should be invested in the study of the abiotic stress responses of plants in their natural habitats. The present review focuses on the possible roles and mechanisms of osmolytes and their association toward abiotic stress tolerance in plants. This review would help the readers in learning more about osmolytes and how they behave in changing environments as well as getting an idea of how this knowledge could be applied to develop stress tolerance in plants.
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4.
Endogenous Polyamines and Ethylene Biosynthesis in Relation to Germination of Osmoprimed Brassica napus Seeds under Salt Stress.
Lechowska, K, Wojtyla, Ł, Quinet, M, Kubala, S, Lutts, S, Garnczarska, M
International journal of molecular sciences. 2021;(1)
Abstract
Currently, seed priming is reported as an efficient and low-cost approach to increase crop yield, which could not only promote seed germination and improve plant growth state but also increase abiotic stress tolerance. Salinity represents one of the most significant abiotic stresses that alters multiple processes in plants. The accumulation of polyamines (PAs) in response to salt stress is one of the most remarkable plant metabolic responses. This paper examined the effect of osmopriming on endogenous polyamine metabolism at the germination and early seedling development of Brassica napus in relation to salinity tolerance. Free, conjugated and bound polyamines were analyzed, and changes in their accumulation were discussed with literature data. The most remarkable differences between the corresponding osmoprimed and unprimed seeds were visible in the free (spermine) and conjugated (putrescine, spermidine) fractions. The arginine decarboxylase pathway seems to be responsible for the accumulation of PAs in primed seeds. The obvious impact of seed priming on tyramine accumulation was also demonstrated. Moreover, the level of ethylene increased considerably in seedlings issued from primed seeds exposed to salt stress. It can be concluded that the polyamines are involved in creating the beneficial effect of osmopriming on germination and early growth of Brassica napus seedlings under saline conditions through moderate changes in their biosynthesis and accumulation.
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Dietary Polyamines Intake and Risk of Colorectal Cancer: A Case-Control Study.
Huang, CY, Fang, YJ, Abulimiti, A, Yang, X, Li, L, Liu, KY, Zhang, X, Feng, XL, Chen, YM, Zhang, CX
Nutrients. 2020;(11)
Abstract
Polyamines (including putrescine, spermidine, and spermine) are small, cationic molecules that are necessary for cell proliferation and differentiation. Few studies have examined the association of dietary polyamines intake with colorectal cancer risk. The aim of this study was to evaluate total polyamines, putrescine, spermidine, and spermine intake in relation to colorectal cancer risk in China. In total, 2502 colorectal cancer cases and 2538 age-(5-year interval) and sex-matched controls were recruited from July 2010 to April 2019. Odds ratios (ORs) and 95% confidence intervals (CI) were calculated by multivariable unconditional logistic regression after adjustment for various potential confounding factors. Higher intake of total polyamine, putrescine and spermidine was significantly associated with reduced risk of colorectal cancer. The adjusted ORs for the highest compared with the lowest quartile of intake were 0.60 (95% CI 0.50, 0.72; Ptrend < 0.001) for total polyamines, 0.35 (95% CI 0.29, 0.43; Ptrend < 0.001) for putrescine and 0.79 (95% CI 0.66, 0.95; Ptrend = 0.001) for spermidine, respectively. However, higher intake of spermine was associated with increased risk of colorectal cancer, with an adjusted OR of 1.58 (95% CI 1.29, 1.93; Ptrend < 0.001). This data indicate that higher intake of total polyamines, putrescine and spermidine, as well as lower intake of spermine, is associated with a decreased risk of colorectal cancer.
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6.
Effect of a lifestyle intervention program with energy-restricted Mediterranean diet and exercise on the serum polyamine metabolome in individuals at high cardiovascular disease risk: a randomized clinical trial.
Fernández-García, JC, Martínez-Sánchez, MA, Bernal-López, MR, Muñoz-Garach, A, Martínez-González, MA, Fitó, M, Salas-Salvadó, J, Tinahones, FJ, Ramos-Molina, B
The American journal of clinical nutrition. 2020;(5):975-982
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Abstract
BACKGROUND Many food items included in the Mediterranean diet (MedDiet) are rich in polyamines, small aliphatic amines with potential cardioprotective effects. The consumption of a MedDiet could increase polyamine concentrations. Based on experimental models, polyamine concentrations may be also influenced by physical activity (PA). OBJECTIVES We aimed to evaluate whether an intervention based on an energy-restricted MedDiet (er-MedDiet) and PA promotion, in comparison with an energy-unrestricted MedDiet and traditional health care, influences the serum pattern of polyamines and related metabolites in subjects at high risk of cardiovascular disease (CVD). METHODS This was a substudy from the PREDIMED-Plus trial, an ongoing randomized clinical trial including 6874 participants allocated either to an intensive weight-loss lifestyle intervention based on er-MedDiet, PA promotion, and behavioral support (er-MedDiet + PA group), or to an energy-unrestricted MedDiet and traditional health care group (MedDiet group). A total of 75 patients (n = 38, er-MedDiet + PA group; n = 37, MedDiet group) were included in this study. Serum concentrations of arginine, ornithine, polyamines, and acetyl polyamines at baseline and 26 wk of intervention were measured by an ultra-high-performance LC-tandem MS platform. RESULTS At week 26, study groups had similar adherence to the MedDiet but patients randomly assigned to the er-MedDiet + PA group showed significantly lower mean energy intake (-340.3 kcal/d; 95% CI: -567.3, -113.4 kcal/d; P = 0.004), higher mean PA (1290.6; 95% CI: 39.9, 2541.3 metabolic equivalent tasks · min/d; P = 0.043), and higher mean decrease in BMI (in kg/m2) (-1.3; 95% CI: -1.8, -0.6; P < 0.001) than the MedDiet group. However, no significant differences in serum polyamines or related metabolites were found between study groups after 26 wk of intervention and no significant between-group differences were found in glycated hemoglobin, HDL-cholesterol, or triglyceride concentrations. CONCLUSIONS In individuals at high CVD risk, an er-MedDiet with increased PA did not result in significant changes of serum concentrations of polyamines or related metabolites in comparison with an energy-unrestricted MedDiet and no increase in PA. This trial was registered at isrctn.com as ISRCTN89898870.
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Dysregulation of multiple metabolic networks related to brain transmethylation and polyamine pathways in Alzheimer disease: A targeted metabolomic and transcriptomic study.
Mahajan, UV, Varma, VR, Griswold, ME, Blackshear, CT, An, Y, Oommen, AM, Varma, S, Troncoso, JC, Pletnikova, O, O'Brien, R, et al
PLoS medicine. 2020;(1):e1003012
Abstract
BACKGROUND There is growing evidence that Alzheimer disease (AD) is a pervasive metabolic disorder with dysregulation in multiple biochemical pathways underlying its pathogenesis. Understanding how perturbations in metabolism are related to AD is critical to identifying novel targets for disease-modifying therapies. In this study, we test whether AD pathogenesis is associated with dysregulation in brain transmethylation and polyamine pathways. METHODS AND FINDINGS We first performed targeted and quantitative metabolomics assays using capillary electrophoresis-mass spectrometry (CE-MS) on brain samples from three groups in the Baltimore Longitudinal Study of Aging (BLSA) (AD: n = 17; Asymptomatic AD [ASY]: n = 13; Control [CN]: n = 13) (overall 37.2% female; mean age at death 86.118 ± 9.842 years) in regions both vulnerable and resistant to AD pathology. Using linear mixed-effects models within two primary brain regions (inferior temporal gyrus [ITG] and middle frontal gyrus [MFG]), we tested associations between brain tissue concentrations of 26 metabolites and the following primary outcomes: group differences, Consortium to Establish a Registry for Alzheimer's Disease (CERAD) (neuritic plaque burden), and Braak (neurofibrillary pathology) scores. We found significant alterations in concentrations of metabolites in AD relative to CN samples, as well as associations with severity of both CERAD and Braak, mainly in the ITG. These metabolites represented biochemical reactions in the (1) methionine cycle (choline: lower in AD, p = 0.003; S-adenosyl methionine: higher in AD, p = 0.005); (2) transsulfuration and glutathione synthesis (cysteine: higher in AD, p < 0.001; reduced glutathione [GSH]: higher in AD, p < 0.001); (3) polyamine synthesis/catabolism (spermidine: higher in AD, p = 0.004); (4) urea cycle (N-acetyl glutamate: lower in AD, p < 0.001); (5) glutamate-aspartate metabolism (N-acetyl aspartate: lower in AD, p = 0.002); and (6) neurotransmitter metabolism (gamma-amino-butyric acid: lower in AD, p < 0.001). Utilizing three Gene Expression Omnibus (GEO) datasets, we then examined mRNA expression levels of 71 genes encoding enzymes regulating key reactions within these pathways in the entorhinal cortex (ERC; AD: n = 25; CN: n = 52) and hippocampus (AD: n = 29; CN: n = 56). Complementing our metabolomics results, our transcriptomics analyses also revealed significant alterations in gene expression levels of key enzymatic regulators of biochemical reactions linked to transmethylation and polyamine metabolism. Our study has limitations: our metabolomics assays measured only a small proportion of all metabolites participating in the pathways we examined. Our study is also cross-sectional, limiting our ability to directly test how AD progression may impact changes in metabolite concentrations or differential-gene expression. Additionally, the relatively small number of brain tissue samples may have limited our power to detect alterations in all pathway-specific metabolites and their genetic regulators. CONCLUSIONS In this study, we observed broad dysregulation of transmethylation and polyamine synthesis/catabolism, including abnormalities in neurotransmitter signaling, urea cycle, aspartate-glutamate metabolism, and glutathione synthesis. Our results implicate alterations in cellular methylation potential and increased flux in the transmethylation pathways, increased demand on antioxidant defense mechanisms, perturbations in intermediate metabolism in the urea cycle and aspartate-glutamate pathways disrupting mitochondrial bioenergetics, increased polyamine biosynthesis and breakdown, as well as abnormalities in neurotransmitter metabolism that are related to AD.
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8.
Biologia futura: the role of polyamine in plant science.
Kamiab, F, Tavassolian, I, Hosseinifarahi, M
Biologia futura. 2020;(3):183-194
Abstract
Polyamines (PAs) are positively charged amines such as putrescine, spermidine and spermine that ubiquitously exist in all organisms. They have been considered as a new type of plant biostimulants, with pivotal roles in many physiological processes. Polyamine levels are controlled by intricate regulatory feedback mechanisms. PAs are directly or indirectly regulated through interaction with signaling metabolites (H202, NO), aminobutyric acid (GABA), phytohormones (abscisic acid, gibberellins, ethylene, cytokinins, auxin, jasmonic acid and brassinosteroids) and nitrogen metabolism (maintaining the balance of C:N in plants). Exogenous applications of PAs enhance the stress resistance, flowering and fruit set, synthesis of bioactive compounds and extension of agricultural crops shelf life. Up-regulation of PAs biosynthesis by genetic manipulation can be a novel strategy to increase the productivity of agricultural crops. Recently, the role of PAs in symbiosis relationships between plants and beneficial microorganisms has been confirmed. PA metabolism has also been targeted to design new harmless fungicides.
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9.
Phytohormones and polyamines regulate plant stress responses by altering GABA pathway.
Podlešáková, K, Ugena, L, Spíchal, L, Doležal, K, De Diego, N
New biotechnology. 2019;:53-65
Abstract
In plants, γ-aminobutyric acid (GABA) accumulates rapidly in response to environmental stress and variations in its endogenous concentration have been shown to affect plant growth. Exogenous application of GABA has also conferred higher stress tolerance by modulating the expression of genes involved in plant signalling, transcriptional regulation, hormone biosynthesis, reactive oxygen species production and polyamine metabolism. Plant hormones play critical roles in adaptation of plants to adverse environmental conditions through a sophisticated crosstalk among them. Several studies have provided evidence for the relationships between GABA, polyamines and hormones such as abscisic acid, cytokinins, auxins, gibberellins and ethylene, among others, focussing on the effect that one specific group of compounds exerts over the metabolic and signalling pathways of others. In this review, we bring together information obtained from plants exposed to several stress conditions and discuss the possible links among these different groups of molecules. The analysis supports the view that highly conserved pathways connect primary and secondary metabolism, with an overlap of regulatory functions related to stress responses and tolerance among phytohormones, amino acids and polyamines.
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10.
Alterations in Polyamine Metabolism in Patients With Lymphangioleiomyomatosis and Tuberous Sclerosis Complex 2-Deficient Cells.
Tang, Y, El-Chemaly, S, Taveira-Dasilva, A, Goldberg, HJ, Bagwe, S, Rosas, IO, Moss, J, Priolo, C, Henske, EP
Chest. 2019;(6):1137-1148
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Abstract
BACKGROUND Lymphangioleiomyomatosis (LAM), a destructive lung disease that affects primarily women, is caused by loss-of-function mutations in TSC1 or TSC2, leading to hyperactivation of mechanistic/mammalian target of rapamycin complex 1 (mTORC1). Rapamycin (sirolimus) treatment suppresses mTORC1 but also induces autophagy, which promotes the survival of TSC2-deficient cells. Based on the hypothesis that simultaneous inhibition of mTORC1 and autophagy would limit the availability of critical nutrients and inhibit LAM cells, we conducted a phase 1 clinical trial of sirolimus and hydroxychloroquine for LAM. Here, we report the analyses of plasma metabolomic profiles from the clinical trial. METHODS We analyzed the plasma metabolome in samples obtained before, during, and after 6 months of treatment with sirolimus and hydroxychloroquine, using univariate statistical models and machine learning approaches. Metabolites and metabolic pathways were validated in TSC2-deficient cells derived from patients with LAM. Single-cell RNA-Seq was employed to assess metabolic enzymes in an early-passage culture from an LAM lung. RESULTS Metabolomic profiling revealed changes in polyamine metabolism during treatment, with 5'-methylthioadenosine and arginine among the most highly upregulated metabolites. Similar findings were observed in TSC2-deficient cells derived from patients with LAM. Single-cell transcriptomic profiling of primary LAM cultured cells revealed that mTORC1 inhibition upregulated key enzymes in the polyamine metabolism pathway, including adenosylmethionine decarboxylase 1. CONCLUSIONS Our data demonstrate that polyamine metabolic pathways are targeted by the combination of rapamycin and hydroxychloroquine, leading to upregulation of 5'-methylthioadenosine and arginine in the plasma of patients with LAM and in TSC2-deficient cells derived from a patient with LAM upon treatment with this drug combination. TRIAL REGISTRY ClinicalTrials.gov; No.: NCT01687179; URL: www.clinicaltrials.gov. Partners Human Research Committee, protocol No. 2012P000669.