-
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 -
Molecules (Basel, Switzerland) Jun 2023Over the past two decades, the strategy of conjugating polyamine tails with bioactive molecules such as anticancer and antimicrobial agents, as well as antioxidant and... (Review)
Review
Over the past two decades, the strategy of conjugating polyamine tails with bioactive molecules such as anticancer and antimicrobial agents, as well as antioxidant and neuroprotective scaffolds, has been widely exploited to enhance their pharmacological profile. Polyamine transport is elevated in many pathological conditions, suggesting that the polyamine portion could improve cellular and subcellular uptake of the conjugate via the polyamine transporter system. In this review, we have presented a glimpse on the polyamine conjugate scenario, classified by therapeutic area, of the last decade with the aim of highlighting achievements and fostering future developments.
Topics: Polyamines; Biological Transport
PubMed: 37298993
DOI: 10.3390/molecules28114518 -
Cells Mar 2022Polyamines are ubiquitous, amine-rich molecules with diverse processes in biology. Recent work has highlighted that polyamines exert profound roles on the mammalian... (Review)
Review
Polyamines are ubiquitous, amine-rich molecules with diverse processes in biology. Recent work has highlighted that polyamines exert profound roles on the mammalian immune system, particularly inflammation and cancer. The mechanisms by which they control immunity are still being described. In the context of inflammation and autoimmunity, polyamine levels inversely correlate to autoimmune phenotypes, with lower polyamine levels associated with higher inflammatory responses. Conversely, in the context of cancer, polyamines and polyamine biosynthetic genes positively correlate with the severity of malignancy. Blockade of polyamine metabolism in cancer results in reduced tumor growth, and the effects appear to be mediated by an increase in T-cell infiltration and a pro-inflammatory phenotype of macrophages. These studies suggest that polyamine depletion leads to inflammation and that polyamine enrichment potentiates myeloid cell immune suppression. Indeed, combinatorial treatment with polyamine blockade and immunotherapy has shown efficacy in pre-clinical models of cancer. Considering the efficacy of immunotherapies is linked to autoimmune sequelae in humans, termed immune-adverse related events (iAREs), this suggests that polyamine levels may govern the inflammatory response to immunotherapies. This review proposes that polyamine metabolism acts to balance autoimmune inflammation and anti-tumor immunity and that polyamine levels can be used to monitor immune responses and responsiveness to immunotherapy.
Topics: Animals; Autoimmunity; Immunotherapy; Inflammation; Mammals; Neoplasms; Polyamines
PubMed: 35269518
DOI: 10.3390/cells11050896 -
Medical Sciences (Basel, Switzerland) May 2021Polycationic polyamines are present in nearly all living organisms and are essential for mammalian cell growth and survival, and for development. These positively... (Review)
Review
Polycationic polyamines are present in nearly all living organisms and are essential for mammalian cell growth and survival, and for development. These positively charged molecules are involved in a variety of essential biological processes, yet their underlying mechanisms of action are not fully understood. Several studies have shown both beneficial and detrimental effects of polyamines on human health. In cancer, polyamine metabolism is frequently dysregulated, and elevated polyamines have been shown to promote tumor growth and progression, suggesting that targeting polyamines is an attractive strategy for therapeutic intervention. In contrast, polyamines have also been shown to play critical roles in lifespan, cardiac health and in the development and function of the brain. Accordingly, a detailed understanding of mechanisms that control polyamine homeostasis in human health and disease is needed to develop safe and effective strategies for polyamine-targeted therapy.
Topics: Cell Proliferation; Homeostasis; Humans; Neoplasms; Polyamines
PubMed: 34068137
DOI: 10.3390/medsci9020028 -
European Journal of Pharmacology Nov 2021Spermine, spermidine and putrescine polyamines are naturally occurring ubiquitous positively charged amines and are essential metabolites for biological functions in our... (Review)
Review
Spermine, spermidine and putrescine polyamines are naturally occurring ubiquitous positively charged amines and are essential metabolites for biological functions in our life. These compounds play a crucial role in many cell processes, including cellular proliferation, growth, and differentiation. Intracellular levels of polyamines depend on their biosynthesis, transport and degradation. Polyamine levels are high in cancer cells, which leads to the promotion of tumor growth, invasion and metastasis. Targeting polyamine metabolism as an anticancer strategy is considerably rational. Due to compensatory mechanisms, a single strategy does not achieve satisfactory clinical effects when using a single agent. Combination regimens are more clinically promising for cancer chemoprevention because they work synergistically with causing little or no adverse effects due to each individual agent being used at lower doses. Moreover, bioactive substances have advantages over single chemical agents because they can affect multiple targets. In this review, we discuss anticancer strategies targeting polyamine metabolism and describe how combination treatments and effective natural active ingredients are promising therapies. The existing research suggests that polyamine metabolic enzymes are important therapeutic targets and that combination therapies can be more effective than monotherapies based on polyamine depletion.
Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Biological Products; Homeostasis; Humans; Neoplasms; Polyamines
PubMed: 34464603
DOI: 10.1016/j.ejphar.2021.174456 -
The Journal of Biological Chemistry Nov 2018Most of the phylogenetic diversity of life is found in bacteria and archaea, and is reflected in the diverse metabolism and functions of bacterial and archaeal... (Review)
Review
Most of the phylogenetic diversity of life is found in bacteria and archaea, and is reflected in the diverse metabolism and functions of bacterial and archaeal polyamines. The polyamine spermidine was probably present in the last universal common ancestor, and polyamines are known to be necessary for critical physiological functions in bacteria, such as growth, biofilm formation, and other surface behaviors, and production of natural products, such as siderophores. There is also phylogenetic diversity of function, indicated by the role of polyamines in planktonic growth of different species, ranging from absolutely essential to entirely dispensable. However, the cellular molecular mechanisms responsible for polyamine function in bacterial growth are almost entirely unknown. In contrast, the molecular mechanisms of essential polyamine functions in archaea are better understood: covalent modification by polyamines of translation factor aIF5A and the agmatine modification of tRNA As with bacterial hyperthermophiles, archaeal thermophiles require long-chain and branched polyamines for growth at high temperatures. For bacterial species in which polyamines are essential for growth, it is still unknown whether the molecular mechanisms underpinning polyamine function involve covalent or noncovalent interactions. Understanding the cellular molecular mechanisms of polyamine function in bacterial growth and physiology remains one of the great challenges for future polyamine research.
Topics: Archaea; Archaeal Proteins; Bacteria; Bacterial Proteins; Polyamines
PubMed: 30254075
DOI: 10.1074/jbc.TM118.005670 -
European Journal of Medicinal Chemistry Oct 2017Naturally occurring polyamines: putrescine, spermidine and spermine are crucial for Kinetoplastid growth and persistence. These aliphatic polycations are either... (Review)
Review
Naturally occurring polyamines: putrescine, spermidine and spermine are crucial for Kinetoplastid growth and persistence. These aliphatic polycations are either biosynthesized or internalized into Kinetoplastid by active transport. Impairing the polyamine metabolism using polyamine derivatives is an interesting path in the search of new antikinetoplastid chemotherapy. In the past 30 years, research interest in this field has been constantly expanding and recent results demonstrated that the discovery of a polyamine-based antikinetoplastid drug is undoubtedly possible. In this paper, all the polyamine derivatives previously described to present an antikinetoplastid activity are reported. This review is organized around three main parts which are diamine, triamine and tetramine derivatives. Each part includes the description of the series of molecules and, their in vitro and in vivo activity when available. Structure-activity relationships of these derivatives are discussed and the most promising structures for a positive outcome are eventually highlighted.
Topics: Animals; Antiprotozoal Agents; Dose-Response Relationship, Drug; Humans; Kinetoplastida; Molecular Structure; Parasitic Sensitivity Tests; Polyamines; Structure-Activity Relationship
PubMed: 28886510
DOI: 10.1016/j.ejmech.2017.08.014 -
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 -
Natural Product Reports Apr 2024Covering: 2005 to August, 2023Polyamine-containing natural products (NPs) have been isolated from a wide range of terrestrial and marine organisms and most of them... (Review)
Review
Covering: 2005 to August, 2023Polyamine-containing natural products (NPs) have been isolated from a wide range of terrestrial and marine organisms and most of them exhibit remarkable and diverse activities, including antimicrobial, antiprotozoal, antiangiogenic, antitumor, antiviral, iron-chelating, anti-depressive, anti-inflammatory, insecticidal, antiobesity, and antioxidant properties. Their extraordinary activities and potential applications in human health and agriculture attract increasing numbers of studies on polyamine-containing NPs. In this review, we summarized the source, structure, classification, bioactivities and biosynthesis of polyamine-containing NPs, focusing on the biosynthetic mechanism of polyamine itself and representative polyamine alkaloids, polyamine-containing siderophores with catechol/hydroxamate/hydroxycarboxylate groups, nonribosomal peptide-(polyketide)-polyamine (NRP-(PK)-PA), and NRP-PK-long chain poly-fatty amine (lcPFAN) hybrid molecules.
Topics: Alkaloids; Anti-Infective Agents; Antineoplastic Agents; Biological Products; Molecular Structure; Polyamines; Siderophores
PubMed: 37873660
DOI: 10.1039/d2np00087c -
Natural Product Reports Oct 2005
Review
Topics: Alkaloids; Animals; Bacteria; Molecular Structure; Plants, Medicinal; Polyamines
PubMed: 16193161
DOI: 10.1039/b413742f