Special Issue "Polyamine Metabolism in Health and Disease: Potential for Polyamine-Targeted Therapies and Prevention"

A special issue of Medical Sciences (ISSN 2076-3271). This special issue belongs to the section "Endocrinology and Metabolic Diseases".

Deadline for manuscript submissions: 31 July 2021.

Special Issue Editor

Dr. Noriyuki Murai
E-Mail Website
Guest Editor
Department of Molecular Biology, The Jikei University School of Medicine, 3‐25‐8 Nishi‐shinbashi, Minato‐ku, Tokyo 105‐8461, Japan
Interests: polyamine metabolism; antizyme; ornithine decarboxylase; ubiquitin-independent protein degradation; proteasome; cancer biology; cancer metabolism

Special Issue Information

Dear Colleagues,

Polyamines are highly charged bioactive substances presented ubiquitously in species from bacteria to humans. Mammalian cells have three major polyamines—putrescine, spermidine, and spermine—at concentrations that range from micromolar to millimolar. Cellular polyamine concentration is highly regulated by polyamine-dependent negative feedback regulation of ornithine decarboxylase (ODC), a rate-limiting enzyme for polyamine biosynthesis. Polyamines are also taken up and exported through putative cellular membrane transporters. The functions of cellular polyamines are highly diversified, and they are involved in cell growth; cell division; apoptosis; autophagy; oxidative stress; ion channel activity; various diseases such as cancer, Alzheimer’s, and Parkinson’s diseases; stroke; and infectious diseases caused by viruses, bacteria, fungi, and parasites. In addition, recent reports suggest that spermidine exerts cardioprotective effects and that its supplementation extends the lifespan of mice through autophagy signaling. In cancer cells, polyamine concentrations are elevated in response to excessive growth signals resulting from amplification and/or abnormalities of oncogenes and/or tumor suppressor genes. Considering these tumor characteristics, difluoromethyl ornithine (DFMO), which is a suicide inhibitor of ODC, was used in clinical trials to suppress tumor growth; however, it had no effect on tumor growth alone. Nevertheless, used in combination with polyamine transport inhibitor, it is likely to be effective for reducing tumor progression. As represented by the Warburg effect, cancer cells have a distinctive metabolic flow compared with normal cells. Accordingly, detailed analysis on polyamine and polyamine-related metabolism, including energy metabolism, will be needed to clarify cancer cell biology and to search therapeutic targets and biomarkers. Recent comprehensive analysis of brain metabolites in patients for Parkinson’s disease suggest that N1, N8-diacetylspermidine levels have the potential to be diagnostic biomarkers of this disease. The aim of this Special Issue of Medical Sciences is to present the latest polyamine research in health and disease and to explore the potential for polyamine-targeted medical applications.

Dr. Noriyuki Murai
Guest Editor

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 papers will be 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. Medical Sciences is an international peer-reviewed open access quarterly 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 1400 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

  • Polyamine metabolism
  • Polyamines in cancer
  • Polyamines in health
  • Polyamines in disease
  • Polyamines in cancer therapy and prevention
  • Polyamines as a biomarker

Published Papers (4 papers)

Order results
Result details
Select all
Export citation of selected articles as:

Research

Jump to: Review

Open AccessArticle
Polyamine-Rich Diet Elevates Blood Spermine Levels and Inhibits Pro-Inflammatory Status: An Interventional Study
Med. Sci. 2021, 9(2), 22; https://doi.org/10.3390/medsci9020022 - 29 Mar 2021
Viewed by 380
Abstract
The Japanese diet and the Mediterranean diet are rich in polyamines (spermidine and spermine). Increased polyamine intake elevated blood spermine levels, inhibited aging-associated pro-inflammatory status (increases in lymphocyte function-associated antigen-1 (LFA-1) on immune cells), suppressed aberrant gene methylation and extended the lifespan of [...] Read more.
The Japanese diet and the Mediterranean diet are rich in polyamines (spermidine and spermine). Increased polyamine intake elevated blood spermine levels, inhibited aging-associated pro-inflammatory status (increases in lymphocyte function-associated antigen-1 (LFA-1) on immune cells), suppressed aberrant gene methylation and extended the lifespan of mice. To test the effects of increased polyamine intake by humans, 30 healthy male volunteers were asked to eat polyamine-rich and ready-to-eat traditional Japanese food (natto) for 12 months. Natto with high polyamine content was used. Another 27 male volunteers were asked not to change their dietary pattern as a control group. The volunteers’ age of intervention and control groups ranged from 40 to 69 years (median 48.9 ± 7.9). Two subjects in the control group subsequently dropped out of the study. The estimated increases in spermidine and spermine intakes were 96.63 ± 47.70 and 22.00 ± 9.56 µmol per day in the intervention group, while no changes were observed in the control group. The mean blood spermine level in the intervention group gradually rose to 1.12 ± 0.29 times the pre-intervention level after 12 months, and were significantly higher (p = 0.019) than those in the control group. Blood spermidine did not increase in either group. LFA-1 on monocytes decreased gradually in the intervention group, and there was an inverse association between changes in spermine concentrations relative to spermidine and changes in LFA-1 levels. Contingency table analysis revealed that the odds ratio to decrease LFA-1 by increased polyamine intake was 3.927 (95% CI 1.116–13.715) (p = 0.032) when the effect of acute inflammation was excluded. The results in the study were similar to those of our animal experiments. Since methylation changes of the entire genome are associated with aging-associated pathologies and our previous studies showed that spermine-induced LFA-1 suppression was associated with the inhibition of aberrant gene methylation, the results suggest that dietary polyamine contributes to human health and longevity. Full article
Show Figures

Figure 1

Open AccessArticle
Effect of Yuzu (Citrus junos) Seed Limonoids and Spermine on Intestinal Microbiota and Hypothalamic Tissue in the Sandhoff Disease Mouse Model
Med. Sci. 2021, 9(1), 17; https://doi.org/10.3390/medsci9010017 - 11 Mar 2021
Viewed by 388
Abstract
The effect of limonoids and spermine (Spm) extracted from yuzu (Citrus junos) seeds on the gut and the brain in a mouse model with Sandhoff disease (SD) was investigated. Wild-type and SD mice were fed a normal diet, or a diet [...] Read more.
The effect of limonoids and spermine (Spm) extracted from yuzu (Citrus junos) seeds on the gut and the brain in a mouse model with Sandhoff disease (SD) was investigated. Wild-type and SD mice were fed a normal diet, or a diet supplemented with limonoid, Spm, or limonoid + Spm for 14–18 weeks, and then 16S rRNA gene amplicon sequencing with extracted DNA from their feces was executed. For SD control mice, intestinal microbiota was mostly composed of Lactobacillus and linked to dysbiosis. For SD and wild-type mice fed with limonoids + Spm or limonoids alone, intestinal microbiota was rich in mucin-degrading bacteria, including Bacteroidetes, Verrucomicrobia, and Firmicutes, and displayed a higher production of short-chain fatty acids and immunoglobulin A. Additionally, SD mice fed with limonoids + Spm or limonoids alone had less inflammation in hypothalamic tissues and displayed a greater number of neurons. Administration of limonoids and/or Spm improved the proportions of beneficial intestinal microbiota to host health and reduced neuronal degeneration in SD mice. Yuzu seed limonoids and Spermine may help to maintain the homeostasis of intestinal microbiota and hypothalamic tissue in the SD mouse model. Full article
Show Figures

Figure 1

Open AccessCommunication
Development of an ELISA for Measurement of Urinary 3-Hydroxypropyl Mercapturic Acid (3-HPMA), the Marker of Stroke
Med. Sci. 2020, 8(3), 33; https://doi.org/10.3390/medsci8030033 - 16 Aug 2020
Viewed by 694
Abstract
We previously observed an inverse correlation between stroke and urinary 3-hydroxypropyl mercapturic acid (3-HPMA), an acrolein-glutathione metabolite, through its measurement by liquid chromatography with tandem mass spectrometry (LC-MS/MS). However, the cost of equipment for LC-MS/MS and its maintenance fee is very expensive and [...] Read more.
We previously observed an inverse correlation between stroke and urinary 3-hydroxypropyl mercapturic acid (3-HPMA), an acrolein-glutathione metabolite, through its measurement by liquid chromatography with tandem mass spectrometry (LC-MS/MS). However, the cost of equipment for LC-MS/MS and its maintenance fee is very expensive and a cost-efficient method is required. In this study, we have developed a sensitive enzyme-linked immunosorbent assay (ELISA) system to measure 3-HPMA using a chicken antibody recognizing 3-HPMA-conjugated chicken albumin as antigen. Linearity to measure 3-HPMA was obtained from 0 to 10 μM, indicating that this ELISA system is useful for measurement of urine 3-HPMA. It was confirmed that 3-HPMA in urine of stroke patients decreased significantly compared with that of control subjects using the ELISA system. Using the ELISA kit, it became possible to evaluate the risk of brain stroke by not only plasma but also by urine. These results confirm that shortage of glutathione to detoxify acrolein is one of the major causes of stroke incidence. Our method contributes to maintenance of quality of life (QOL) of the elderly. Full article
Show Figures

Figure 1

Review

Jump to: Research

Open AccessReview
Health-Promoting Effects of Dietary Polyamines
Med. Sci. 2021, 9(1), 8; https://doi.org/10.3390/medsci9010008 - 05 Feb 2021
Viewed by 476
Abstract
The purpose of this paper is to summarize the latest information on the various aspects of polyamines and their health benefits. In recent years, attempts to treat cancer by reducing elevated polyamines levels in cancer cells have been made, with some advancing to [...] Read more.
The purpose of this paper is to summarize the latest information on the various aspects of polyamines and their health benefits. In recent years, attempts to treat cancer by reducing elevated polyamines levels in cancer cells have been made, with some advancing to clinical trials. However, it has been reported since 2009 that polyamines extend the healthy life span of animals by inducing autophagy, protecting the kidneys and liver, improving cognitive function, and inhibiting the progression of heart diseases. As such, there is conflicting information regarding the relationship between polyamines and health. However, attempts to treat cancer by decreasing intracellular polyamines levels are a coping strategy to suppress the proliferation-promoting effects of polyamines, and a consensus is being reached that polyamine intake does not induce cancer in healthy individuals. To provide further scientific evidence for the health-promoting effects of polyamines, large-scale clinical studies involving multiple groups are expected in the future. It is also important to promote basic research on polyamine intake in animals, including elucidation of the polyamine balance between food, intestinal bacteria, and biosynthesis. Full article
Show Figures

Figure 1

Back to TopTop