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Biomolecules
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Polyamine Metabolism and Function
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Polyamine Metabolism and Function

A special issue of Biomolecules (ISSN 2218-273X). This special issue belongs to the section "Cellular Biochemistry".

Deadline for manuscript submissions: closed (31 December 2023) | Viewed by 17734

Special Issue Editors

Prof. Dr. Manuela Cervelli

E-Mail Website
Guest Editor
Dipartimento di Scienze, Università degli studi Roma Tre, 00154 Rome, Italy
Interests: polyamines; spermine oxidase; polyamine metabolism; excitotoxicity; glutammate transmission; circRNA
Dr. Marianna Nicoletta Rossi

E-Mail Website
Guest Editor
Dipartimento di Scienze, Università degli studi Roma Tre, 00154 Rome, Italy
Interests: molecular biology; gene expression; epigenetics; lncRNA; inflammation; muscle differentiation; cytokines

Special Issue Information

Dear Colleagues,

The polyamines putrescine, spermidine and spermine are polycations ubiquitously present in cells where they exert pleiotropic functions in cellular mechanisms like proliferation, protein synthesis (through the hypusination of the transcription factor EIF5a), redox balance, and different forms of cell death (including but not restricted to ferroptosis and autophagy). Accordingly, dysregulation of polyamine content has been found in many human diseases including cancer and neurodegeneration, as well as during aging. In particular, polyamine biosynthesis and intra/extracellular trafficking are frequently dysregulated in cancers and polyamine depletion strategies have been tested for reducing tumor growth. Polyamines are also known as inhibitors of both innate and adaptative immune responses and have been observed to be immune suppressors in the tumor microenvironment. The intracellular content of polyamines is the result of endogenous biosynthesis, catabolism, uptake from the extracellular space, and excretion. Polyamine metabolism utilizes the cofactors dcSAM and acetyl-CoA also involved in protein/DNA methylation and protein acetylation, linking polyamines to epigenetic regulation of gene expression.

This Special Issue aims at discussing new insight into the molecular mechanisms regulating polyamine metabolism and polyamine functions in cellular pathophysiology. We welcome authors to submit original research or review articles that cover the following themes:

  • Molecular mechanisms of polyamines metabolism regulation (including synthesis, catabolism and transport).
  • Alteration of polyamine content in different cellular types and organs and their association to pathological conditions.
  • Polyamines regulation/dysregulation in different model organisms.
  • Polyamines in animal and cellular models of diseases.
  • Mechanisms of polyamines dysregulation in a cancer model.
  • Role of polyamines in neuronal diseases, including cognitive impairment, Alzheimer’s and Parkinson’s diseases, excitotoxicity.
  • Role of polyamines in transcription regulation.
  • Role of polyamines in epigenetic regulation.
  • Role of polyamines in specific subcellular compartments (for example, but not restricted to mitochondria, peroxisomes, nucleus).
  • Multiple roles of spermidine in cellular physiology and pathology.

We look forward to receiving your contributions.

Prof. Dr. Manuela Cervelli
Dr. Marianna Nicoletta Rossi
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biomolecules is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  •  polyamines
  •  spermidine
  •  aging
  •  eiF5A
  •  metabolism
  •  cancer
  •  molecular mechanisms
  •  ROS
  •  Autophagy
  •  regulation of transcription
  •  epigenetic regulation
  •  polyamine metabolic enzymes
  •  neurodegeneration

Published Papers (11 papers)

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Research

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17 pages, 3064 KiB  
Article
Enhancing the Spermidine Synthase-Based Polyamine Biosynthetic Pathway to Boost Rapid Growth in Marine Diatom Phaeodactylum tricornutum
by Hung-Yun Lin, Chung-Hsiao Liu, Yong-Ting Kang, Sin-Wei Lin, Hsin-Yun Liu, Chun-Ting Lee, Yu-Chen Liu, Man-Chun Hsu, Ya-Yun Chien, Shao-Ming Hong, Yun-Hsuan Cheng, Bing-You Hsieh and Han-Jia Lin
Biomolecules 2024, 14(3), 372; https://doi.org/10.3390/biom14030372 - 19 Mar 2024
Viewed by 815
Abstract
Diatoms, efficient carbon capture organisms, contribute to 20% of global carbon fixation and 40% of ocean primary productivity, garnering significant attention to their growth. Despite their significance, the synthesis mechanism of polyamines (PAs), especially spermidine (Spd), which are crucial for growth in various [...] Read more.
Diatoms, efficient carbon capture organisms, contribute to 20% of global carbon fixation and 40% of ocean primary productivity, garnering significant attention to their growth. Despite their significance, the synthesis mechanism of polyamines (PAs), especially spermidine (Spd), which are crucial for growth in various organisms, remains unexplored in diatoms. This study reveals the vital role of Spd, synthesized through the spermidine synthase (SDS)-based pathway, in the growth of the diatom Phaeodactylum tricornutum. PtSDS1 and PtSDS2 in the P. tricornutum genome were confirmed as SDS enzymes through enzyme-substrate selectivity assays. Their distinct activities are governed primarily by the Y79 active site. Overexpression of a singular gene revealed that PtSDS1, PtSDS2, and PtSAMDC from the SDS-based synthesis pathway are all situated in the cytoplasm, with no significant impact on PA content or diatom growth. Co-overexpression of PtSDS1 and PtSAMDC proved essential for elevating Spd levels, indicating multifactorial regulation. Elevated Spd content promotes diatom growth, providing a foundation for exploring PA functions and regulation in diatoms. Full article
(This article belongs to the Special Issue Polyamine Metabolism and Function)
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23 pages, 4508 KiB  
Article
The Development of LAT1 Efflux Agonists as Mechanistic Probes of Cellular Amino Acid Stress
by Vandana Sekhar, Houssine Ikhlef, Alexandra Bunea, Viet S. Nguyen, Johan Joo, Mukund P. Tantak, Holly Moots and Otto Phanstiel IV
Biomolecules 2024, 14(3), 326; https://doi.org/10.3390/biom14030326 - 09 Mar 2024
Viewed by 983
Abstract
Amino acid restriction induces cellular stress and cells often respond via the induction of autophagy. Autophagy or ‘self-eating’ enables the recycling of proteins and provides the essential amino acids needed for cell survival. Of the naturally occurring amino acids, methionine restriction has pleiotropic [...] Read more.
Amino acid restriction induces cellular stress and cells often respond via the induction of autophagy. Autophagy or ‘self-eating’ enables the recycling of proteins and provides the essential amino acids needed for cell survival. Of the naturally occurring amino acids, methionine restriction has pleiotropic effects on cells because methionine also contributes to the intracellular methyl pools required for epigenetic controls as well as polyamine biosynthesis. In this report, we describe the chemical synthesis of four diastereomers of a methionine depletion agent and demonstrate how controlled methionine efflux from cells significantly reduces intracellular methionine, S-adenosylmethionine (SAM), S-adenosyl homocysteine (SAH), and polyamine levels. We also demonstrate that human pancreatic cancer cells respond via a lipid signaling pathway to induce autophagy. The methionine depletion agent causes the large amino acid transporter 1 (LAT1) to preferentially work in reverse and export the cell’s methionine (and leucine) stores. The four diastereomers of the lead methionine/leucine depletion agent were synthesized and evaluated for their ability to (a) efflux 3H-leucine from cells, (b) dock to LAT1 in silico, (c) modulate intracellular SAM, SAH, and phosphatidylethanolamine (PE) pools, and (d) induce the formation of the autophagy-associated LC3-II marker. The ability to modulate the intracellular concentration of methionine regardless of exogenous methionine supply provides new molecular tools to better understand cancer response pathways. This information can then be used to design improved therapeutics that target downstream methionine-dependent processes like polyamines. Full article
(This article belongs to the Special Issue Polyamine Metabolism and Function)
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Graphical abstract

14 pages, 2275 KiB  
Article
Impact of Difluoromethylornithine and AMXT 1501 on Gene Expression and Capsule Regulation in Streptococcus pneumoniae
by Moses B. Ayoola, Leslie A. Shack, Otto Phanstiel IV and Bindu Nanduri
Biomolecules 2024, 14(2), 178; https://doi.org/10.3390/biom14020178 - 02 Feb 2024
Viewed by 946
Abstract
Streptococcus pneumoniae (Spn), a Gram-positive bacterium, poses a significant threat to human health, causing mild respiratory infections to severe invasive conditions. Despite the availability of vaccines, challenges persist due to serotype replacement and antibiotic resistance, emphasizing the need for alternative therapeutic strategies. This [...] Read more.
Streptococcus pneumoniae (Spn), a Gram-positive bacterium, poses a significant threat to human health, causing mild respiratory infections to severe invasive conditions. Despite the availability of vaccines, challenges persist due to serotype replacement and antibiotic resistance, emphasizing the need for alternative therapeutic strategies. This study explores the intriguing role of polyamines, ubiquitous, small organic cations, in modulating virulence factors, especially the capsule, a crucial determinant of Spn’s pathogenicity. Using chemical inhibitors, difluoromethylornithine (DFMO) and AMXT 1501, this research unveils distinct regulatory effects on the gene expression of the Spn D39 serotype in response to altered polyamine homeostasis. DFMO inhibits polyamine biosynthesis, disrupting pathways associated with glucose import and the interconversion of sugars. In contrast, AMXT 1501, targeting polyamine transport, enhances the expression of polyamine and glucose biosynthesis genes, presenting a novel avenue for regulating the capsule independent of glucose availability. Despite ample glucose availability, AMXT 1501 treatment downregulates the glycolytic pathway, fatty acid synthesis, and ATP synthase, crucial for energy production, while upregulating two-component systems responsible for stress management. This suggests a potential shutdown of energy production and capsule biosynthesis, redirecting resources towards stress management. Following DFMO and AMXT 1501 treatments, countermeasures, such as upregulation of stress response genes and ribosomal protein, were observed but appear to be insufficient to overcome the deleterious effects on capsule production. This study highlights the complexity of polyamine-mediated regulation in S. pneumoniae, particularly capsule biosynthesis. Our findings offer valuable insights into potential therapeutic targets for modulating capsules in a polyamine-dependent manner, a promising avenue for intervention against S. pneumoniae infections. Full article
(This article belongs to the Special Issue Polyamine Metabolism and Function)
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14 pages, 10178 KiB  
Article
Spermine Oxidase–Substrate Electrostatic Interactions: The Modulation of Enzyme Function by Neighboring Colloidal ɣ-Fe2O3
by Graziano Rilievo, Massimiliano Magro, Federica Tonolo, Alessandro Cecconello, Lavinia Rutigliano, Aura Cencini, Simone Molinari, Maria Luisa Di Paolo, Cristian Fiorucci, Marianna Nicoletta Rossi, Manuela Cervelli and Fabio Vianello
Biomolecules 2023, 13(12), 1800; https://doi.org/10.3390/biom13121800 - 15 Dec 2023
Viewed by 918
Abstract
Protein–nanoparticle hybridization can ideally lead to novel biological entities characterized by emerging properties that can sensibly differ from those of the parent components. Herein, the effect of ionic strength on the biological functions of recombinant His-tagged spermine oxidase (i.e., SMOX) was studied for [...] Read more.
Protein–nanoparticle hybridization can ideally lead to novel biological entities characterized by emerging properties that can sensibly differ from those of the parent components. Herein, the effect of ionic strength on the biological functions of recombinant His-tagged spermine oxidase (i.e., SMOX) was studied for the first time. Moreover, SMOX was integrated into colloidal surface active maghemite nanoparticles (SAMNs) via direct self-assembly, leading to a biologically active nano-enzyme (i.e., SAMN@SMOX). The hybrid was subjected to an in-depth chemical–physical characterization, highlighting the fact that the protein structure was perfectly preserved. The catalytic activity of the nanostructured hybrid (SAMN@SMOX) was assessed by extracting the kinetics parameters using spermine as a substrate and compared to the soluble enzyme as a function of ionic strength. The results revealed that the catalytic function was dominated by electrostatic interactions and that they were drastically modified upon hybridization with colloidal ɣ-Fe2O3. The fact that the affinity of SMOX toward spermine was significantly higher for the nanohybrid at low salinity is noteworthy. The present study supports the vision of using protein–nanoparticle conjugation as a means to modulate biological functions. Full article
(This article belongs to the Special Issue Polyamine Metabolism and Function)
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14 pages, 3908 KiB  
Article
Indomethacin Induces Spermidine/Spermine-N1-Acetyltransferase-1 via the Nucleolin-CDK1 Axis and Synergizes with the Polyamine Oxidase Inhibitor Methoctramine in Lung Cancer Cells
by Neudo Buelvas, Isidora Ugarte-Vio, Laura Asencio-Leal, Matías Muñoz-Uribe, Antonia Martin-Martin, Alejandro Rojas-Fernández, José A. Jara, Julio C. Tapia, María Elena Arias and Rodrigo A. López-Muñoz
Biomolecules 2023, 13(9), 1383; https://doi.org/10.3390/biom13091383 - 12 Sep 2023
Cited by 1 | Viewed by 1085
Abstract
Indomethacin is a non-selective NSAID used against pain and inflammation. Although cyclooxygenase (COX) inhibition is considered indomethacin’s primary action mechanism, COX-independent ways are associated with beneficial effects in cancer. In colon cancer cells, the activation of the peroxisome proliferator-activated receptor-γ (PPAR-γ) is related [...] Read more.
Indomethacin is a non-selective NSAID used against pain and inflammation. Although cyclooxygenase (COX) inhibition is considered indomethacin’s primary action mechanism, COX-independent ways are associated with beneficial effects in cancer. In colon cancer cells, the activation of the peroxisome proliferator-activated receptor-γ (PPAR-γ) is related to the increase in spermidine/spermine-N1-acetyltransferase-1 (SSAT-1), a key enzyme for polyamine degradation, and related to cell cycle arrest. Indomethacin increases the SSAT-1 levels in lung cancer cells; however, the mechanism relying on the SSAT-1 increase is unclear. Thus, we asked for the influence of the PPAR-γ on the SSAT-1 expression in two lung cancer cell lines: H1299 and A549. We found that the inhibition of PPAR-γ with GW9662 did not revert the increase in SSAT-1 induced by indomethacin. Because the mRNA of SSAT-1 suffers a pre-translation retention step by nucleolin, a nucleolar protein, we explored the relationship between indomethacin and the upstream translation regulators of SSAT-1. We found that indomethacin decreases the nucleolin levels and the cyclin-dependent kinase 1 (CDK1) levels, which phosphorylates nucleolin in mitosis. Overexpression of nucleolin partially reverts the effect of indomethacin over cell viability and SSAT-1 levels. On the other hand, Casein Kinase, known for phosphorylating nucleolin during interphase, is not modified by indomethacin. SSAT-1 exerts its antiproliferative effect by acetylating polyamines, a process reverted by the polyamine oxidase (PAOX). Recently, methoctramine was described as the most specific inhibitor of PAOX. Thus, we asked if methoctramine could increase the effect of indomethacin. We found that, when combined, indomethacin and methoctramine have a synergistic effect against NSCLC cells in vitro. These results suggest that indomethacin increases the SSAT-1 levels by reducing the CDK1-nucleolin regulatory axis, and the PAOX inhibition with methoctramine could improve the antiproliferative effect of indomethacin. Full article
(This article belongs to the Special Issue Polyamine Metabolism and Function)
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17 pages, 8812 KiB  
Article
ATP13A4 Upregulation Drives the Elevated Polyamine Transport System in the Breast Cancer Cell Line MCF7
by Sarah van Veen, Antria Kourti, Elke Ausloos, Joris Van Asselberghs, Chris Van den Haute, Veerle Baekelandt, Jan Eggermont and Peter Vangheluwe
Biomolecules 2023, 13(6), 918; https://doi.org/10.3390/biom13060918 - 31 May 2023
Viewed by 1659
Abstract
Polyamine homeostasis is disturbed in several human diseases, including cancer, which is hallmarked by increased intracellular polyamine levels and an upregulated polyamine transport system (PTS). Thus far, the polyamine transporters contributing to the elevated levels of polyamines in cancer cells have not yet [...] Read more.
Polyamine homeostasis is disturbed in several human diseases, including cancer, which is hallmarked by increased intracellular polyamine levels and an upregulated polyamine transport system (PTS). Thus far, the polyamine transporters contributing to the elevated levels of polyamines in cancer cells have not yet been described, despite the fact that polyamine transport inhibitors are considered for cancer therapy. Here, we tested whether the upregulation of candidate polyamine transporters of the P5B transport ATPase family is responsible for the increased PTS in the well-studied breast cancer cell line MCF7 compared to the non-tumorigenic epithelial breast cell line MCF10A. We found that MCF7 cells presented elevated expression of a previously uncharacterized P5B-ATPase, ATP13A4, which was responsible for the elevated polyamine uptake activity. Furthermore, MCF7 cells were more sensitive to polyamine cytotoxicity, as demonstrated by cell viability, cell death and clonogenic assays. Importantly, the overexpression of ATP13A4 WT in MCF10A cells induced a MCF7 polyamine phenotype, with significantly higher uptake of BODIPY-labeled polyamines and increased sensitivity to polyamine toxicity. In conclusion, we established ATP13A4 as a new polyamine transporter in the human PTS and showed that ATP13A4 may play a major role in the increased polyamine uptake of breast cancer cells. ATP13A4 therefore emerges as a candidate therapeutic target for anticancer drugs that block the PTS. Full article
(This article belongs to the Special Issue Polyamine Metabolism and Function)
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15 pages, 998 KiB  
Article
C-Methylated Spermidine Derivatives: Convenient Syntheses and Antizyme-Related Effects
by Maxim A. Khomutov, Arthur I. Salikhov, Vladimir A. Mitkevich, Vera L. Tunitskaya, Olga A. Smirnova, Sergey P. Korolev, Alexander O. Chizhov, Marina B. Gottikh, Sergey N. Kochetkov and Alex R. Khomutov
Biomolecules 2023, 13(6), 916; https://doi.org/10.3390/biom13060916 - 31 May 2023
Viewed by 989
Abstract
The biogenic polyamines, spermidine (Spd) and spermine (Spm), are present at millimolar concentrations in all eukaryotic cells, where they participate in the regulation of vitally important cellular functions. Polyamine analogs and derivatives are a traditional and important instrument for the investigation of the [...] Read more.
The biogenic polyamines, spermidine (Spd) and spermine (Spm), are present at millimolar concentrations in all eukaryotic cells, where they participate in the regulation of vitally important cellular functions. Polyamine analogs and derivatives are a traditional and important instrument for the investigation of the cellular functions of polyamines, enzymes of their metabolism, and the regulation of the biosynthesis of antizyme—a key downregulator of polyamine homeostasis. Here, we describe convenient gram-scale syntheses of a set of C-methylated analogs of Spd. The biochemical properties of these compounds and the possibility for the regulation of their activity by moving a methyl group along the polyamine backbone and by changing the stereochemistry of the chiral center(s) are discussed. Full article
(This article belongs to the Special Issue Polyamine Metabolism and Function)
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20 pages, 21947 KiB  
Article
Transcriptome Analysis of Redox Systems and Polyamine Metabolic Pathway in Hepatoma and Non-Tumor Hepatocyte-like Cells
by Olga N. Ivanova, George S. Krasnov, Anastasiya V. Snezhkina, Anna V. Kudryavtseva, Vyacheslav S. Fedorov, Natalia F. Zakirova, Michail V. Golikov, Sergey N. Kochetkov, Birke Bartosch, Vladimir T. Valuev-Elliston and Alexander V. Ivanov
Biomolecules 2023, 13(4), 714; https://doi.org/10.3390/biom13040714 - 21 Apr 2023
Cited by 1 | Viewed by 1982
Abstract
Reactive oxygen species (ROS) play a major role in the regulation of various processes in the cell. The increase in their production is a factor contributing to the development of numerous pathologies, including inflammation, fibrosis, and cancer. Accordingly, the study of ROS production [...] Read more.
Reactive oxygen species (ROS) play a major role in the regulation of various processes in the cell. The increase in their production is a factor contributing to the development of numerous pathologies, including inflammation, fibrosis, and cancer. Accordingly, the study of ROS production and neutralization, as well as redox-dependent processes and the post-translational modifications of proteins, is warranted. Here, we present a transcriptomic analysis of the gene expression of various redox systems and related metabolic processes, such as polyamine and proline metabolism and the urea cycle in Huh7.5 hepatoma cells and the HepaRG liver progenitor cell line, that are widely used in hepatitis research. In addition, changes in response to the activation of polyamine catabolism that contribute to oxidative stress were studied. In particular, differences in the gene expression of various ROS-producing and ROS-neutralizing proteins, the enzymes of polyamine metabolisms and proline and urea cycles, as well as calcium ion transporters between cell lines, are shown. The data obtained are important for understanding the redox biology of viral hepatitis and elucidating the influence of the laboratory models used. Full article
(This article belongs to the Special Issue Polyamine Metabolism and Function)
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18 pages, 2619 KiB  
Article
Novel Green Fluorescent Polyamines to Analyze ATP13A2 and ATP13A3 Activity in the Mammalian Polyamine Transport System
by Marine Houdou, Nathalie Jacobs, Jonathan Coene, Mujahid Azfar, Roeland Vanhoutte, Chris Van den Haute, Jan Eggermont, Veronique Daniëls, Steven H. L. Verhelst and Peter Vangheluwe
Biomolecules 2023, 13(2), 337; https://doi.org/10.3390/biom13020337 - 09 Feb 2023
Cited by 3 | Viewed by 2562
Abstract
Cells acquire polyamines putrescine (PUT), spermidine (SPD) and spermine (SPM) via the complementary actions of polyamine uptake and synthesis pathways. The endosomal P5B-type ATPases ATP13A2 and ATP13A3 emerge as major determinants of mammalian polyamine uptake. Our biochemical evidence shows that fluorescently [...] Read more.
Cells acquire polyamines putrescine (PUT), spermidine (SPD) and spermine (SPM) via the complementary actions of polyamine uptake and synthesis pathways. The endosomal P5B-type ATPases ATP13A2 and ATP13A3 emerge as major determinants of mammalian polyamine uptake. Our biochemical evidence shows that fluorescently labeled polyamines are genuine substrates of ATP13A2. They can be used to measure polyamine uptake in ATP13A2- and ATP13A3-dependent cell models resembling radiolabeled polyamine uptake. We further report that ATP13A3 enables faster and stronger cellular polyamine uptake than does ATP13A2. We also compared the uptake of new green fluorescent PUT, SPD and SPM analogs using different coupling strategies (amide, triazole or isothiocyanate) and fluorophores (symmetrical BODIPY, BODIPY-FL and FITC). ATP13A2 promotes the uptake of various SPD and SPM analogs, whereas ATP13A3 mainly stimulates the uptake of PUT and SPD conjugates. However, the polyamine linker and coupling position on the fluorophore impacts the transport capacity, whereas replacing the fluorophore affects polyamine selectivity. The highest uptake in ATP13A2 or ATP13A3 cells is observed with BODIPY-FL-amide conjugated to SPD, whereas BODIPY-PUT analogs are specifically taken up via ATP13A3. We found that P5B-type ATPase isoforms transport fluorescently labeled polyamine analogs with a distinct structure–activity relationship (SAR), suggesting that isoform-specific polyamine probes can be designed. Full article
(This article belongs to the Special Issue Polyamine Metabolism and Function)
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Review

Jump to: Research

12 pages, 1509 KiB  
Review
The Role of Spermidine and Its Key Metabolites in Important, Pathogenic Human Viruses and in Parasitic Infections Caused by Plasmodium falciparum and Trypanosoma brucei
by Annette Kaiser
Biomolecules 2023, 13(5), 803; https://doi.org/10.3390/biom13050803 - 09 May 2023
Cited by 2 | Viewed by 2613
Abstract
The triamine spermidine is a key metabolite of the polyamine pathway. It plays a crucial role in many infectious diseases caused by viral or parasitic infections. Spermidine and its metabolizing enzymes, i.e., spermidine/spermine-N1-acetyltransferase, spermine oxidase, acetyl polyamine oxidase, and deoxyhypusine synthase, [...] Read more.
The triamine spermidine is a key metabolite of the polyamine pathway. It plays a crucial role in many infectious diseases caused by viral or parasitic infections. Spermidine and its metabolizing enzymes, i.e., spermidine/spermine-N1-acetyltransferase, spermine oxidase, acetyl polyamine oxidase, and deoxyhypusine synthase, fulfill common functions during infection in parasitic protozoa and viruses which are obligate, intracellular parasites. The competition for this important polyamine between the infected host cell and the pathogen determines the severity of infection in disabling human parasites and pathogenic viruses. Here, we review the impact of spermidine and its metabolites in disease development of the most important, pathogenic human viruses such as SARS-CoV-2, HIV, Ebola, and in the human parasites Plasmodium and Trypanosomes. Moreover, state-of-the-art translational approaches to manipulate spermidine metabolism in the host and the pathogen are discussed to accelerate drug development against these threatful, infectious human diseases. Full article
(This article belongs to the Special Issue Polyamine Metabolism and Function)
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15 pages, 3666 KiB  
Review
Molecular Characteristics of Toxicity of Acrolein Produced from Spermine
by Keiko Kashiwagi and Kazuei Igarashi
Biomolecules 2023, 13(2), 298; https://doi.org/10.3390/biom13020298 - 04 Feb 2023
Cited by 10 | Viewed by 1831
Abstract
Acrolein (CH2=CH-CHO), an unsaturated aldehyde produced from spermine, is one of the major contributors to oxidative stress. Acrolein has been found to be more toxic than reactive oxygen species (H2O2 and •OH), and it can be easily conjugated [...] Read more.
Acrolein (CH2=CH-CHO), an unsaturated aldehyde produced from spermine, is one of the major contributors to oxidative stress. Acrolein has been found to be more toxic than reactive oxygen species (H2O2 and •OH), and it can be easily conjugated with proteins, bringing about changes in nature of the proteins. Acrolein is detoxified by glutathione in cells and was found to be mainly produced from spermine through isolating two cell lines of acrolein-resistant Neuro2a cells. The molecular characteristics of acrolein toxicity and tissue damage elicited by acrolein were investigated. It was found that glyceraldehyde-3-phosphate dehydrogenase (GAPDH); cytoskeleton proteins such as vimentin, actin, α- and β-tubulin proteins; and apolipoprotein B-100 (ApoB100) in LDL are strongly damaged by acrolein conjugation. In contrast, activities of matrix metalloproteinase-9 (MMP-9) and proheparanase (proHPSE) are enhanced, and antibody-recognizing abilities of immunoglobulins are modified by acrolein conjugation, resulting in aggravation of diseases. The functional changes of these proteins by acrolein have been elucidated at the molecular level. The findings confirmed that acrolein is the major contributor causing tissue damage in the elderly. Full article
(This article belongs to the Special Issue Polyamine Metabolism and Function)
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