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Bioscience, Biotechnology, and... Jul 2022Polyamines (putrescine, spermidine, and spermine) are compounds with amino groups at both ends of a hydrocarbon. Polyamines produced by intestinal bacteria suppress... (Review)
Review
Polyamines (putrescine, spermidine, and spermine) are compounds with amino groups at both ends of a hydrocarbon. Polyamines produced by intestinal bacteria suppress chronic inflammation and enhance the intestinal barrier in the colon, and are also transferred into the blood via the colonic epithelium, resulting in significant improvement of host cognitive performance and life extension in mice. Upregulation of polyamine production by gut microbes can help compensate for the aging-associated decrease in polyamine content through the uptake of intestinal luminal polyamine, thereby extending the healthy life expectancy of the host. This review summarizes recent advances in the study of polyamine metabolism and transport in gut microbes, with particular reference to Escherichia coli and the most predominant species of the gut microbiota. Furthermore, we describe polyamine production by a novel hybrid system comprised of multiple gut microbes, as well as from high-polyamine-producing lactic acid bacteria derived from fermented foods.
Topics: Animals; Biological Transport; Escherichia coli; Gastrointestinal Microbiome; Mice; Polyamines; Putrescine; Spermidine; Spermine
PubMed: 35648468
DOI: 10.1093/bbb/zbac080 -
World Journal of Microbiology &... Oct 2017Polyamines are small polycations that are well conserved in all the living organisms except Archae, Methanobacteriales and Halobacteriales. The most common polyamines... (Review)
Review
Polyamines are small polycations that are well conserved in all the living organisms except Archae, Methanobacteriales and Halobacteriales. The most common polyamines are putrescine, spermidine and spermine, which exist in varying concentrations in different organisms. They are involved in a variety of cellular processes such as gene expression, cell growth, survival, stress response and proliferation. Therefore, diverse regulatory pathways are evolved to ensure strict regulation of polyamine concentration in the cells. Polyamine levels are kept under strict control by biosynthetic pathways as well as cellular uptake driven by specific transporters. Reverse genetic studies in microorganisms showed that deletion of the genes in polyamine metabolic pathways or depletion of polyamines have negative effects on cell survival and proliferation. The protein products of these genes are also used as drug targets against pathogenic protozoa. These altogether confirm the significant roles of polyamines in the cells. This mini-review focuses on the differential concentrations of polyamines and their cellular functions in different microorganisms. This will provide an insight about the diverse evolution of polyamine metabolism and function based on the physiology and the ecological context of the microorganisms.
Topics: Bacteria; Biosynthetic Pathways; Cell Cycle; Eukaryota; Fungi; Gene Regulatory Networks; Microbial Viability; Polyamines; Stress, Physiological
PubMed: 29080149
DOI: 10.1007/s11274-017-2370-y -
International Journal of Molecular... Sep 2019Acute kidney injury (AKI) refers to an abrupt decrease in kidney function. It affects approximately 7% of all hospitalized patients and almost 35% of intensive care... (Review)
Review
Acute kidney injury (AKI) refers to an abrupt decrease in kidney function. It affects approximately 7% of all hospitalized patients and almost 35% of intensive care patients. Mortality from acute kidney injury remains high, particularly in critically ill patients, where it can be more than 50%. The primary causes of AKI include ischemia/reperfusion (I/R), sepsis, or nephrotoxicity; however, AKI patients may present with a complicated etiology where many of the aforementioned conditions co-exist. Multiple bio-markers associated with renal damage, as well as metabolic and signal transduction pathways that are involved in the mediation of renal dysfunction have been identified as a result of the examination of models, patient samples, and clinical data of AKI of disparate etiologies. These discoveries have enhanced our ability to diagnose AKIs and to begin to elucidate the mechanisms involved in their pathogenesis. Studies in our laboratory revealed that the expression and activity of spermine/spermidine N-acetyltransferase (SAT1), the rate-limiting enzyme in polyamine back conversion, were enhanced in kidneys of rats after I/R injury. Additional studies revealed that the expression of spermine oxidase (SMOX), another critical enzyme in polyamine catabolism, is also elevated in the kidney and other organs subjected to I/R, septic, toxic, and traumatic injuries. The maladaptive role of polyamine catabolism in the mediation of AKI and other injuries has been clearly demonstrated. This review will examine the biochemical and mechanistic basis of tissue damage brought about by enhanced polyamine degradation and discuss the potential of therapeutic interventions that target polyamine catabolic enzymes or their byproducts for the treatment of AKI.
Topics: Acetyltransferases; Acute Kidney Injury; Animals; Biomarkers; Gene Expression; Gene Expression Regulation, Enzymologic; Humans; Metabolic Networks and Pathways; Oxidoreductases Acting on CH-NH Group Donors; Polyamines; Polyamine Oxidase
PubMed: 31561575
DOI: 10.3390/ijms20194790 -
Molecules (Basel, Switzerland) Nov 2023Polyamines participate in the processes of cell growth and development. The degradation branch of their metabolism involves amine oxidases. The oxidation of spermine,... (Review)
Review
Polyamines participate in the processes of cell growth and development. The degradation branch of their metabolism involves amine oxidases. The oxidation of spermine, spermidine and putrescine releases hydrogen peroxide and the corresponding aminoaldehyde. Polyamine-derived aminoaldehydes have been found to be cytotoxic, and they represent the subject of this review. 3-aminopropanal disrupts the lysosomal membrane and triggers apoptosis or necrosis in the damaged cells. It is implicated in the pathogenesis of cerebral ischemia. Furthermore, 3-aminopropanal yields acrolein through the elimination of ammonia. This reactive aldehyde is also generated by the decomposition of aminoaldehydes produced in the reaction of serum amine oxidase with spermidine or spermine. In addition, acrolein is a common environmental pollutant. It causes covalent modifications of proteins, including carbonylation, the production of Michael-type adducts and cross-linking, and it has been associated with inflammation-related diseases. APAL and acrolein are detoxified by aldehyde dehydrogenases and other mechanisms. High-performance liquid chromatography, immunochemistry and mass spectrometry have been largely used to analyze the presence of polyamine-derived aminoaldehydes and protein modifications elicited by their effect. However, the main and still open challenge is to find clues for discovering clear linkages between aldehyde-induced modifications of specific proteins and the development of various diseases.
Topics: Polyamines; Acrolein; Spermidine; Spermine; Aldehydes
PubMed: 37959847
DOI: 10.3390/molecules28217429 -
Cell Communication and Signaling : CCS Dec 2023Polyamines are essential for the growth and proliferation of mammalian cells and are intimately involved in biological mechanisms such as DNA replication, RNA... (Review)
Review
Polyamines are essential for the growth and proliferation of mammalian cells and are intimately involved in biological mechanisms such as DNA replication, RNA transcription, protein synthesis, and post-translational modification. These mechanisms regulate cellular proliferation, differentiation, programmed cell death, and the formation of tumors. Several studies have confirmed the positive effect of polyamines on the maintenance of health, while others have demonstrated that their activity may promote the occurrence and progression of diseases. This review examines a variety of topics, such as polyamine source and metabolism, including metabolism, transport, and the potential impact of polyamines on health and disease. In addition, a brief summary of the effects of oncogenes and signaling pathways on tumor polyamine metabolism is provided. Video Abstract.
Topics: Animals; Humans; Polyamines; Apoptosis; RNA; Neoplasms; Cell Proliferation; Mammals
PubMed: 38049863
DOI: 10.1186/s12964-023-01373-0 -
Biochimica Et Biophysica Acta. General... Sep 2018Polyamines are ubiquitous positively charged amines found in all organisms. These molecules play a crucial role in many biological functions including cell growth, gene... (Review)
Review
Polyamines are ubiquitous positively charged amines found in all organisms. These molecules play a crucial role in many biological functions including cell growth, gene regulation and differentiation. The three major polyamines produced in all mammalian cells are putrescine, spermidine and spermine. The intracellular levels of these polyamines depend on the interplay of the biosynthetic and catabolic enzymes of the polyamine and methionine salvage pathway, as well as the involvement of polyamine transporters. Polyamine levels are observed to be high in cancer cells, which contributes to malignant transformation, cell proliferation and poor patient prognosis. Considering the critical roles of polyamines in cancer cell proliferation, numerous anti-polyaminergic compounds have been developed as anti-tumor agents, which seek to suppress polyamine levels by specifically inhibiting polyamine biosynthesis, activating polyamine catabolism, or blocking polyamine transporters. However, in terms of the development of effective anti-cancer therapeutics targeting the polyamine system, these efforts have unfortunately resulted in little success. Recently, several studies using the iron chelators, O-trensox and ICL670A (Deferasirox), have demonstrated a decline in both iron and polyamine levels. Since iron levels are also high in cancer cells, and like polyamines, are required for proliferation, these latter findings suggest a biochemically integrated link between iron and polyamine metabolism.
Topics: Animals; Cell Proliferation; Humans; Neoplasms; Polyamines
PubMed: 29890242
DOI: 10.1016/j.bbagen.2018.06.004 -
JCI Insight Sep 2023Glutaminolysis is a hallmark of the activation and metabolic reprogramming of T cells. Isotopic tracer analyses of antigen-activated effector CD8+ T cells revealed that...
Glutaminolysis is a hallmark of the activation and metabolic reprogramming of T cells. Isotopic tracer analyses of antigen-activated effector CD8+ T cells revealed that glutamine is the principal carbon source for the biosynthesis of polyamines putrescine, spermidine, and spermine. These metabolites play critical roles in activation-induced T cell proliferation, as well as for the production of hypusine, which is derived from spermidine and is covalently linked to the translation elongation factor eukaryotic translation initiation factor 5A (eIF5A). Here, we demonstrated that the glutamine/polyamine/hypusine axis controlled the expression of CD69, an important regulator of tissue-resident memory T cells (Trm). Inhibition of this circuit augmented the development of Trm cells ex vivo and in vivo in the BM, a well-established niche for Trm cells. Furthermore, blocking the polyamine/hypusine axis augmented CD69 expression as well as IFN-γ and TNF-α production in (a) human CD8+ T cells from peripheral blood and sarcoma tumor infiltrating lymphocytes and (b) human CD8+ CAR-T cells. Collectively, these findings support the notion that the polyamine-hypusine circuit can be exploited to modulate Trm cells for therapeutic benefit.
Topics: Humans; Polyamines; Spermidine; Memory T Cells; Glutamine; CD8-Positive T-Lymphocytes
PubMed: 37581943
DOI: 10.1172/jci.insight.169308 -
Microbiology and Molecular Biology... Dec 2017Polyamines are small, abundant, aliphatic molecules present in all mammalian cells. Within the context of the cell, they play a myriad of roles, from modulating nucleic... (Review)
Review
Polyamines are small, abundant, aliphatic molecules present in all mammalian cells. Within the context of the cell, they play a myriad of roles, from modulating nucleic acid conformation to promoting cellular proliferation and signaling. In addition, polyamines have emerged as important molecules in virus-host interactions. Many viruses have been shown to require polyamines for one or more aspects of their replication cycle, including DNA and RNA polymerization, nucleic acid packaging, and protein synthesis. Understanding the role of polyamines has become easier with the application of small-molecule inhibitors of polyamine synthesis and the use of interferon-induced regulators of polyamines. Here we review the diverse mechanisms in which viruses require polyamines and investigate blocking polyamine synthesis as a potential broad-spectrum antiviral approach.
Topics: Animals; Antiviral Agents; DNA, Viral; Disease Models, Animal; Host-Pathogen Interactions; Humans; Mice; Polyamines; RNA, Viral; Viral Proteins; Virus Diseases; Virus Replication
PubMed: 28904024
DOI: 10.1128/MMBR.00029-17 -
Methods in Molecular Biology (Clifton,... 2018Polyamines (PAs) are essential biomolecules that are known to be involved in the regulation of many plant developmental and growth processes as well as their response to... (Review)
Review
Polyamines (PAs) are essential biomolecules that are known to be involved in the regulation of many plant developmental and growth processes as well as their response to different environmental stimuli. Maintaining the cellular pools of PAs or their metabolic precursors and by-products is critical to accomplish their normal functions. Therefore, the titre of PAs in the cells must be under tight regulation to enable cellular PA homeostasis. Polyamine homeostasis is hence achieved by the regulation of their input into the cellular PA pool, their conversion into secondary metabolites, their transport to other issues/organs, and their catabolism or turnover. The major contributors of input to the PA pools are their in vivo biosynthesis, interconversion between different PAs, and transport from other tissues/organs; while the output or turnover of PAs is facilitated by transport, conjugation and catabolism. Polyamine metabolic pathways including the biosynthesis, catabolism/turnover and conjugation with various organic molecules have been widely studied in all kingdoms. Discoveries on the molecular transporters facilitating the intracellular and intercellular translocation of PAs have also been reported. Numerous recent studies using transgenic approaches and mutagenesis have shown that plants can tolerate quite large concentrations of PAs in the cells; even though, at times, high cellular accumulation of PAs is quite detrimental, and so is high rate of catabolism. The mechanism by which plants tolerate such large quantities of PAs is still unclear. Interestingly, enhanced PA biosynthesis via manipulation of the PA metabolic networks has been suggested to contribute directly to increased growth and improvements in plant abiotic and biotic stress responses; hence greater biomass and productivity. Genetic manipulation of the PA metabolic networks has also been shown to improve plant nitrogen assimilation capacity, which may in turn lead to enhanced carbon assimilation. These potential benefits on top of the widely accepted role of PAs in improving plants' tolerance to biotic and abiotic stressors are invaluable tools for future plant improvement strategies.
Topics: Biological Transport; Citric Acid Cycle; Glutamic Acid; Metabolic Networks and Pathways; Nitric Oxide; Nitrogen; Plants; Polyamines; Proline; Spermine
PubMed: 29080151
DOI: 10.1007/978-1-4939-7398-9_1 -
Marine Drugs Dec 2018Microalgae of different evolutionary origins are typically found in rivers, lakes, and oceans, providing more than 45% of global primary production. They provide not... (Review)
Review
Microalgae of different evolutionary origins are typically found in rivers, lakes, and oceans, providing more than 45% of global primary production. They provide not only a food source for animals, but also affect microbial ecosystems through symbioses with microorganisms or secretion of some metabolites. Derived from amino acids, polyamines are present in almost all types of organisms, where they play important roles in maintaining physiological functions or against stress. Microalgae can produce a variety of distinct polyamines, and the polyamine content is important to meet the physiological needs of microalgae and may also affect other species in the environment. In addition, some polyamines produced by microalgae have medical or nanotechnological applications. Previous studies on several types of microalgae have indicated that the putative polyamine metabolic pathways may be as complicated as the genomes of these organisms, which contain genes originating from plants, animals, and even bacteria. There are also several novel polyamine synthetic routes in microalgae. Understanding the nature of polyamines in microalgae will not only improve our knowledge of microalgal physiology and ecological function, but also provide valuable information for biotechnological applications.
Topics: Adaptation, Physiological; Biosynthetic Pathways; Biotechnology; Cell Division; Microalgae; Photosynthesis; Polyamines; Stress, Physiological
PubMed: 30577419
DOI: 10.3390/md17010001