Research

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9 pages, 1097 KiB

Open AccessArticle

The Role of Spermidine Synthase (SpdS) and Spermine Synthase (Sms) in Regulating Triglyceride Storage in Drosophila

by Tahj S. Morales, Erik C. Avis, Elise K. Paskowski, Hamza Shabar, Shannon L. Nowotarski and Justin R. DiAngelo

Med. Sci. 2021, 9(2), 27; https://0-doi-org.brum.beds.ac.uk/10.3390/medsci9020027 - 02 May 2021

Cited by 5 | Viewed by 2644

Abstract

Polyamines are small organic cations that are important for several biological processes such as cell proliferation, cell cycle progression, and apoptosis. The dysregulation of intracellular polyamines is often associated with diseases such as cancer, diabetes, and developmental disorders. Although polyamine metabolism has been [...] Read more.

Polyamines are small organic cations that are important for several biological processes such as cell proliferation, cell cycle progression, and apoptosis. The dysregulation of intracellular polyamines is often associated with diseases such as cancer, diabetes, and developmental disorders. Although polyamine metabolism has been well studied, the effects of key enzymes in the polyamine pathway on lipid metabolism are not well understood. Here, we determined metabolic effects resulting from the absence of spermidine synthase (SpdS) and spermine synthase (Sms) in Drosophila. While SpdS mutants developed normally and accumulated triglycerides, Sms mutants had reduced viability and stored less triglyceride than the controls. Interestingly, when decreasing SpdS and Sms, specifically in the fat body, triglyceride storage increased. While there was no difference in triglycerides stored in heads, thoraxes and abdomen fat bodies, abdomen fat body DNA content increased, and protein/DNA decreased in both SpdS- and Sms-RNAi flies, suggesting that fat body-specific knockdown of SpdS and Sms causes the production of smaller fat body cells and triglycerides to accumulate in non-fat body tissues of the abdomen. Together, these data provide support for the role that polyamines play in the regulation of metabolism and can help enhance our understanding of polyamine function in metabolic diseases. Full article

(This article belongs to the Special Issue Polyamine Metabolism in Health and Disease: Potential for Polyamine-Targeted Therapies and Prevention)

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14 pages, 761 KiB

Open AccessArticle

Polyamine-Rich Diet Elevates Blood Spermine Levels and Inhibits Pro-Inflammatory Status: An Interventional Study

by Kuniyasu Soda, Takeshi Uemura, Hidenori Sanayama, Kazuei Igarashi and Taro Fukui

Med. Sci. 2021, 9(2), 22; https://0-doi-org.brum.beds.ac.uk/10.3390/medsci9020022 - 29 Mar 2021

Cited by 22 | Viewed by 5035

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

(This article belongs to the Special Issue Polyamine Metabolism in Health and Disease: Potential for Polyamine-Targeted Therapies and Prevention)

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19 pages, 4924 KiB

Open AccessArticle

Effect of Yuzu (Citrus junos) Seed Limonoids and Spermine on Intestinal Microbiota and Hypothalamic Tissue in the Sandhoff Disease Mouse Model

by Mayumi Minamisawa, Takuma Suzumura, Sudeep Bose, Tetsuyuki Taniai, Gota Kawai, Kyoko Suzuki, Akira Yamaguchi and Shoji Yamanaka

Med. Sci. 2021, 9(1), 17; https://0-doi-org.brum.beds.ac.uk/10.3390/medsci9010017 - 11 Mar 2021

Cited by 3 | Viewed by 3121

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

(This article belongs to the Special Issue Polyamine Metabolism in Health and Disease: Potential for Polyamine-Targeted Therapies and Prevention)

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8 pages, 621 KiB

Open AccessCommunication

Development of an ELISA for Measurement of Urinary 3-Hydroxypropyl Mercapturic Acid (3-HPMA), the Marker of Stroke

by Akihiko Sakamoto, Takeshi Uemura, Yusuke Terui, Madoka Yoshida, Kazumasa Fukuda, Takao Nakamura, Keiko Kashiwagi and Kazuei Igarashi

Med. Sci. 2020, 8(3), 33; https://0-doi-org.brum.beds.ac.uk/10.3390/medsci8030033 - 16 Aug 2020

Cited by 3 | Viewed by 2362

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

(This article belongs to the Special Issue Polyamine Metabolism in Health and Disease: Potential for Polyamine-Targeted Therapies and Prevention)

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Review

Jump to: Research

32 pages, 1739 KiB

Open AccessReview

Polyamine Metabolism in Leishmania Parasites: A Promising Therapeutic Target

by Nicola S. Carter, Yumena Kawasaki, Surbhi S. Nahata, Samira Elikaee, Sara Rajab, Leena Salam, Mohammed Y. Alabdulal, Kelli K. Broessel, Forogh Foroghi, Alyaa Abbas, Reyhaneh Poormohamadian and Sigrid C. Roberts

Med. Sci. 2022, 10(2), 24; https://0-doi-org.brum.beds.ac.uk/10.3390/medsci10020024 - 22 Apr 2022

Cited by 8 | Viewed by 3684

Abstract

Parasites of the genus Leishmania cause a variety of devastating and often fatal diseases in humans and domestic animals worldwide. The need for new therapeutic strategies is urgent because no vaccine is available, and treatment options are limited due to a lack of [...] Read more.

Parasites of the genus Leishmania cause a variety of devastating and often fatal diseases in humans and domestic animals worldwide. The need for new therapeutic strategies is urgent because no vaccine is available, and treatment options are limited due to a lack of specificity and the emergence of drug resistance. Polyamines are metabolites that play a central role in rapidly proliferating cells, and recent studies have highlighted their critical nature in Leishmania. Numerous studies using a variety of inhibitors as well as gene deletion mutants have elucidated the pathway and routes of transport, revealing unique aspects of polyamine metabolism in Leishmania parasites. These studies have also shed light on the significance of polyamines for parasite proliferation, infectivity, and host–parasite interactions. This comprehensive review article focuses on the main polyamine biosynthetic enzymes: ornithine decarboxylase, S-adenosylmethionine decarboxylase, and spermidine synthase, and it emphasizes recent discoveries that advance these enzymes as potential therapeutic targets against Leishmania parasites. Full article

(This article belongs to the Special Issue Polyamine Metabolism in Health and Disease: Potential for Polyamine-Targeted Therapies and Prevention)

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21 pages, 1544 KiB

Open AccessReview

Polyamines: Functions, Metabolism, and Role in Human Disease Management

by Narashans Alok Sagar, Swarnava Tarafdar, Surbhi Agarwal, Ayon Tarafdar and Sunil Sharma

Med. Sci. 2021, 9(2), 44; https://0-doi-org.brum.beds.ac.uk/10.3390/medsci9020044 - 09 Jun 2021

Cited by 66 | Viewed by 6901

Abstract

Putrescine, spermine, and spermidine are the important polyamines (PAs), found in all living organisms. PAs are formed by the decarboxylation of amino acids, and they facilitate cell growth and development via different cellular responses. PAs are the integrated part of the cellular and [...] Read more.

Putrescine, spermine, and spermidine are the important polyamines (PAs), found in all living organisms. PAs are formed by the decarboxylation of amino acids, and they facilitate cell growth and development via different cellular responses. PAs are the integrated part of the cellular and genetic metabolism and help in transcription, translation, signaling, and post-translational modifications. At the cellular level, PA concentration may influence the condition of various diseases in the body. For instance, a high PA level is detrimental to patients suffering from aging, cognitive impairment, and cancer. The levels of PAs decline with age in humans, which is associated with different health disorders. On the other hand, PAs reduce the risk of many cardiovascular diseases and increase longevity, when taken in an optimum quantity. Therefore, a controlled diet is an easy way to maintain the level of PAs in the body. Based on the nutritional intake of PAs, healthy cell functioning can be maintained. Moreover, several diseases can also be controlled to a higher extend via maintaining the metabolism of PAs. The present review discusses the types, important functions, and metabolism of PAs in humans. It also highlights the nutritional role of PAs in the prevention of various diseases. Full article

(This article belongs to the Special Issue Polyamine Metabolism in Health and Disease: Potential for Polyamine-Targeted Therapies and Prevention)

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17 pages, 577 KiB

Open AccessReview

Polyamine Homeostasis in Development and Disease

by Shima Nakanishi and John L. Cleveland

Med. Sci. 2021, 9(2), 28; https://0-doi-org.brum.beds.ac.uk/10.3390/medsci9020028 - 13 May 2021

Cited by 29 | Viewed by 3975

Abstract

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 [...] Read more.

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. Full article

(This article belongs to the Special Issue Polyamine Metabolism in Health and Disease: Potential for Polyamine-Targeted Therapies and Prevention)

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8 pages, 4785 KiB

Open AccessReview

Health-Promoting Effects of Dietary Polyamines

by Rika Hirano, Hideto Shirasawa and Shin Kurihara

Med. Sci. 2021, 9(1), 8; https://0-doi-org.brum.beds.ac.uk/10.3390/medsci9010008 - 05 Feb 2021

Cited by 20 | Viewed by 4130

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

(This article belongs to the Special Issue Polyamine Metabolism in Health and Disease: Potential for Polyamine-Targeted Therapies and Prevention)

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