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Polyamines in Aging and Disease

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Endocrinology and Metabolism".

Deadline for manuscript submissions: closed (30 April 2024) | Viewed by 9836

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Special Issue Editors

Dr. Takeshi Uemura

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Guest Editor

Department of Pharmaceutical Sciences, Faculty of Pharmaceutical Sciences, Josai University, Saitama 330-0295, Japan
Interests: polyamines; polyamine oxidase; ageing; spermine oxidase; brain stroke

Prof. Dr. Yusuke Terui

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Guest Editor

Faculty of Pharmacy, Chiba Institute of Science, Chiba 288-0025, Japan
Interests: polyamine; cell proliferation; cell viability; Escherichia coli; spermine; eEF1A; biofilm; spermidine; Shine–Dalgarno sequence; oxidative stress; CR sequence; glutathione; SoxR; GshA; BMAL1; circadian rhythm; clock gene; bio-molecules; polyamine modulon; regulation of metabolic rhythm

Special Issue Information

Dear Colleagues,

Polyamines are bioactive amines found in almost all living organisms and are essential for normal cellular functions. The number of polyamines in cells is tightly regulated by metabolism: biosynthesis, degradation, and transport. Recent studies have shown that disturbances in polyamine metabolism are associated with aging and disease. Age-related reductions in polyamines have been shown to lead to reduced cognitive and physical function. In cancer, on the other hand, high levels of polyamines have been suggested to lead to a worse prognosis. As the global population ages, there is a need for technologies to prevent and overcome aging and various diseases and to extend healthy life spans. The aim of this Special Issue is to deepen our knowledge of the relationship between polyamines and aging and disease. This Special Issue invites contributors to publish important work that will clarify the relationship between polyamines and aging and disease and extend the healthy life span by preventing and overcoming various diseases.

Dr. Takeshi Uemura
Prof. Dr. Yusuke Terui
Guest Editors

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Keywords

polyamines
bioactive amines
aging
senility
old people
spermine
spermidine
polyamine metabolism
polyamine oxidase
polyamine analogues
metabolic diseases in the elderly

Published Papers (6 papers)

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Research

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17 pages, 10753 KiB

Open AccessArticle

In Silico and In Vitro Approach for Evaluation of the Anti-Inflammatory and Antioxidant Potential of Mygalin

by Abraham Espinoza-Culupú, Nayara Del Santos, Mariella Farfán-López, Elizabeth Mendes, Pedro Ismael da Silva Junior and Monamaris Marques Borges

Int. J. Mol. Sci. 2023, 24(23), 17019; https://doi.org/10.3390/ijms242317019 - 30 Nov 2023

Viewed by 975

Abstract

There is a great interest in describing new molecules to be used as therapeutic targets in various diseases, particularly those that play a role in inflammatory responses and infection control. Mygalin is a synthetic analogue of spermidine, and previous studies have demonstrated its bactericidal effect against Escherichia coli, as well as its ability to modulate the inflammatory response of macrophages against lipopolysaccharide (LPS). However, the mechanisms through which mygalin regulates this inflammatory response remain poorly characterized. A set of platforms using molecular docking analysis was employed to analyze various properties of mygalin, including toxicity, biodistribution, absorption, and the prediction of its anti-inflammatory properties. In in vitro assays, we evaluated the potential of mygalin to interact with products of the inflammatory response, such as reactive oxygen species (ROS) and antioxidant activity, using the BMDM cell. The in silico analyses indicated that mygalin is not toxic, and can interact with proteins from the kinase group, and enzymes and receptors in eukaryotic cells. Molecular docking analysis showed interactions with key amino acid residues of COX-2, iNOS and 5-LOX enzymes. In vitro, assays demonstrated a significant reduction in the expression of iNOS and COX-2 induced by LPS, along with a decrease in the oxidative stress caused by the treatment with PMA, all without altering cell viability. Mygalin exhibited robust antioxidant activity in DPPH assays, regardless of the dose used, and inhibited heat-induced hemolysis. These studies suggest that mygalin holds promise for further investigation as a new molecule with anti-inflammatory and antioxidant properties. Full article

(This article belongs to the Special Issue Polyamines in Aging and Disease)

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9 pages, 2402 KiB

Open AccessArticle

Inhibition of Polyamine Catabolism Reduces Cellular Senescence

by Takeshi Uemura, Miki Matsunaga, Yuka Yokota, Koichi Takao and Takemitsu Furuchi

Int. J. Mol. Sci. 2023, 24(17), 13397; https://doi.org/10.3390/ijms241713397 - 29 Aug 2023

Viewed by 1437

Abstract

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. Full article

(This article belongs to the Special Issue Polyamines in Aging and Disease)

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11 pages, 1812 KiB

Open AccessArticle

Transient Receptor Potential Ankyrin 1 (TRPA1) Channel Mediates Acrolein Cytotoxicity in Human Lung Cancer Cells

by Akihiko Sakamoto, Yusuke Terui, Kazuei Igarashi and Keiko Kashiwagi

Int. J. Mol. Sci. 2023, 24(14), 11847; https://doi.org/10.3390/ijms241411847 - 24 Jul 2023

Viewed by 1113

Abstract

Transient receptor potential ankyrin 1 (TRPA1) is a nonselective ion channel implicated in thermosensation and inflammatory pain. It has been reported that expression of the TRPA1 channel is induced by cigarette smoke extract. Acrolein found in cigarette smoke is highly toxic and known as an agonist of the TRPA1 channel. However, the role of TRPA1 in the cytotoxicity of acrolein remains unclear. Here, we investigated whether the TRPA1 channel is involved in the cytotoxicity of acrolein in human lung cancer A549 cells. The IC₅₀ of acrolein in A549 cells was 25 μM, and acrolein toxicity increased in a concentration- and time-dependent manner. When the effect of acrolein on TRPA1 expression was examined, the expression of TRPA1 in A549 cells was increased by treatment with 50 μM acrolein for 24 h or 500 μM acrolein for 30 min. AP-1, a transcription factor, was activated in the cells treated with 50 μM acrolein for 24 h, while induction of NF-κB and HIF-1α was observed in the cells treated with 500 μM acrolein for 30 min. These results suggest that acrolein induces TRPA1 expression by activating these transcription factors. Overexpression of TRPA1 in A549 cells increased acrolein sensitivity and the level of protein-conjugated acrolein (PC-Acro), while knockdown of TRPA1 in A549 cells or treatment with a TRPA1 antagonist caused tolerance to acrolein. These findings suggest that acrolein induces the TRPA1 channel and that an increase in TRPA1 expression promotes the cytotoxicity of acrolein. Full article

(This article belongs to the Special Issue Polyamines in Aging and Disease)

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10 pages, 1715 KiB

Open AccessArticle

Levilactobacillus brevis with High Production of Putrescine Isolated from Blue Cheese and Its Application

by Yuta Ami, Narumi Kodama, Masahiro Umeda, Hanae Nakamura, Hideto Shirasawa, Takashi Koyanagi and Shin Kurihara

Int. J. Mol. Sci. 2023, 24(11), 9668; https://doi.org/10.3390/ijms24119668 - 02 Jun 2023

Cited by 1 | Viewed by 1834

Abstract

Polyamine intake has been reported to help extend the lifespan of animals. Fermented foods contain high concentrations of polyamines, produced by fermenting bacteria. Therefore, the bacteria, isolated from fermented foods that produce large amounts of polyamines, are potentially used as a source of polyamines for humans. In this study, the strain Levilactobacillus brevis FB215, which has the ability to accumulate approximately 200 µM of putrescine in the culture supernatant, was isolated from fermented foods, specifically the Blue Stilton cheese. Furthermore, L. brevis FB215 synthesized putrescine from agmatine and ornithine, which are known polyamine precursors. When cultured in the extract of Sakekasu, a byproduct obtained during the brewing of Japanese rice wine containing high levels of both agmatine and ornithine, L. brevis FB215 grew to OD₆₀₀ = 1.7 after 83 h of cultivation and accumulated high concentrations (~1 mM) of putrescine in the culture supernatant. The fermentation product also did not contain histamine or tyramine. The Sakekasu-derived ingredient fermented by the food-derived lactic acid bacteria developed in this study could contribute to increasing polyamine intake in humans. Full article

(This article belongs to the Special Issue Polyamines in Aging and Disease)

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Review

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17 pages, 2315 KiB

Open AccessReview

The Molecular Role of Polyamines in Age-Related Diseases: An Update

by Guadalupe Elizabeth Jimenez Gutierrez, Fabiola V. Borbolla Jiménez, Luis G. Muñoz, Yessica Sarai Tapia Guerrero, Nadia Mireya Murillo Melo, José Melesio Cristóbal-Luna, Norberto Leyva Garcia, Joaquín Cordero-Martínez and Jonathan J. Magaña

Int. J. Mol. Sci. 2023, 24(22), 16469; https://doi.org/10.3390/ijms242216469 - 17 Nov 2023

Cited by 1 | Viewed by 2159

Abstract

Polyamines (Pas) are short molecules that exhibit two or three amine groups that are positively charged at a physiological pH. These small molecules are present in high concentrations in a wide variety of organisms and tissues, suggesting that they play an important role in cellular physiology. Polyamines include spermine, spermidine, and putrescine, which play important roles in age-related diseases that have not been completely elucidated. Aging is a natural process, defined as the time-related deterioration of the physiological functions; it is considered a risk factor for degenerative diseases such as cardiovascular, neurodegenerative, and musculoskeletal diseases; arthritis; and even cancer. In this review, we provide a new perspective on the participation of Pas in the cellular and molecular processes related to age-related diseases, focusing our attention on important degenerative diseases such as Alzheimerߣs disease, Parkinsonߣs disease, osteoarthritis, sarcopenia, and osteoporosis. This new perspective leads us to propose that Pas function as novel biomarkers for age-related diseases, with the main purpose of achieving new molecular alternatives for healthier aging. Full article

(This article belongs to the Special Issue Polyamines in Aging and Disease)

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15 pages, 1519 KiB

Open AccessReview

Polyamines in Ovarian Aging and Disease

by Bo Kang, Xin Wang, Xiaoguang An, Chengweng Ji, Weikang Ling, Yuxin Qi, Shuo Li and Dongmei Jiang

Int. J. Mol. Sci. 2023, 24(20), 15330; https://doi.org/10.3390/ijms242015330 - 18 Oct 2023

Viewed by 1429

Abstract

Ovarian aging and disease-related decline in fertility are challenging medical and economic issues with an increasing prevalence. Polyamines are a class of polycationic alkylamines widely distributed in mammals. They are small molecules essential for cell growth and development. Polyamines alleviate ovarian aging through various biological processes, including reproductive hormone synthesis, cell metabolism, programmed cell death, etc. However, an abnormal increase in polyamine levels can lead to ovarian damage and promote the development of ovarian disease. Therefore, polyamines have long been considered potential therapeutic targets for aging and disease, but their regulatory roles in the ovary deserve further investigation. This review discusses the mechanisms by which polyamines ameliorate human ovarian aging and disease through different biological processes, such as autophagy and oxidative stress, to develop safe and effective polyamine targeted therapy strategies for ovarian aging and the diseases. Full article

(This article belongs to the Special Issue Polyamines in Aging and Disease)

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