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Biomedicines
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The Role of Polyamines in Human Health and Disease
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The Role of Polyamines in Human Health and Disease

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Immunology and Immunotherapy".

Deadline for manuscript submissions: closed (30 September 2023) | Viewed by 9996

Special Issue Editor

Dr. Kuniyasu Soda

E-Mail Website
Guest Editor
Cardiovascular Research Institute, Saitama Medical Center, Jichi Medical University, Saitama City, Saitama 330-8503, Japan
Interests: polyamine; human health; human diseases
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

There has been an accumulation of knowledge by many researchers on polyamines. Polyamines are essential for the survival and function of all living organisms. In recent years, polyamines have been reported to be associated with healthy longevity and various areas of disease that have not been previously examined. Unfortunately, however, some of these studies have been conducted without fully understanding the properties of polyamines that have been accumulated to date. Furthermore, because of this, the effects of polyamine degradation products have been erroneously reported as the direct effects of polyamines. Therefore, in this Special Issue, we would like to accumulate new findings on polyamines for healthy longevity and polyamines and diseases, based on a full understanding of conventional findings and the characteristics of polyamines. We invite papers on polyamines and health, including basic research, clinical studies, and even epidemiological studies.

Dr. Kuniyasu Soda
Guest Editor

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Keywords

  • polyamine
  • spermine
  • spermidine
  • health
  • longevity
  • disease

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Published Papers (5 papers)

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16 pages, 13768 KiB  
Article
Polyamine Catabolism and Its Role in Renal Injury and Fibrosis in Mice Subjected to Repeated Low-Dose Cisplatin Treatment
by Kamyar Zahedi, Sharon Barone, Marybeth Brooks, Tracy Murray Stewart, Jackson R. Foley, Ashley Nwafor, Robert A. Casero, Jr. and Manoocher Soleimani
Biomedicines 2024, 12(3), 640; https://doi.org/10.3390/biomedicines12030640 - 13 Mar 2024
Viewed by 1675
Abstract
Cisplatin, a chemotherapeutic agent, can cause nephrotoxic and ototoxic injuries. Using a mouse model of repeated low dose cisplatin (RLDC), we compared the kidneys of cisplatin- and vehicle-treated mice on days 3 (early injury phase) and 35 (late injury/recovery phase) after the final [...] Read more.
Cisplatin, a chemotherapeutic agent, can cause nephrotoxic and ototoxic injuries. Using a mouse model of repeated low dose cisplatin (RLDC), we compared the kidneys of cisplatin- and vehicle-treated mice on days 3 (early injury phase) and 35 (late injury/recovery phase) after the final treatment. RNA-seq analyses revealed increases in the expression of markers of kidney injury (e.g., lipocalin 2 and kidney injury molecule 1) and fibrosis (e.g., collagen 1, fibronectin, and vimentin 1) in RLDC mice. In addition, we observed increased expression of polyamine catabolic enzymes (spermidine/spermine N1-acetyltransferase, Sat1, and spermine oxidase, Smox) and decreased expression of ornithine decarboxylase (Odc1), a rate-limiting enzyme in polyamine synthesis in mice subjected to RLDC. Upon confirmation of the RNA-seq results, we tested the hypothesis that enhanced polyamine catabolism contributes to the onset of renal injury and development of fibrosis. To test our hypothesis, we compared the severity of RLDC-induced renal injury and fibrosis in wildtype (WT), Sat1-KO, and Smox-KO mice. Our results suggest that the ablation of polyamine catabolic enzymes reduces the severity of renal injury and that modulation of the activity of these enzymes may protect against kidney damage and fibrosis caused by cisplatin treatment. Full article
(This article belongs to the Special Issue The Role of Polyamines in Human Health and Disease)
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12 pages, 2260 KiB  
Article
Loss of Anti-Tumor Efficacy by Polyamine Blocking Therapy in GCN2 Null Mice
by Eric T. Alexander, Erin Fahey, Otto Phanstiel IV and Susan K. Gilmour
Biomedicines 2023, 11(10), 2703; https://doi.org/10.3390/biomedicines11102703 - 5 Oct 2023
Cited by 1 | Viewed by 1518
Abstract
GCN2 is one of the main sensors of amino acid starvation stress, and its activation in the stressful tumor microenvironment plays a crucial role in tumor survival and progression. We hypothesized that elevated polyamine biosynthesis and subsequent depletion of precursor arginine activates GCN2, [...] Read more.
GCN2 is one of the main sensors of amino acid starvation stress, and its activation in the stressful tumor microenvironment plays a crucial role in tumor survival and progression. We hypothesized that elevated polyamine biosynthesis and subsequent depletion of precursor arginine activates GCN2, thus rewiring metabolism to support tumor cell survival and drive myeloid immunosuppressive function. We sought to determine if the anti-tumor efficacy of a polyamine blocking therapy (PBT) may be mediated by its effect on GCN2. Unlike wild-type mice, PBT treatment in GCN2 knockout mice bearing syngeneic B16.F10 or EG7 tumors resulted in no tumor growth inhibition and no changes in the profile of infiltrating tumor immune cells. Studies with murine bone marrow cell cultures showed that increased polyamine metabolism and subsequent arginine depletion and GCN2 activation played an essential role in the generation and cytoprotective autophagy of myeloid derived suppressor cells (MDSCs) as well as the M2 polarization and survival of macrophages, all of which were inhibited by PBT. In all, our data suggest that polyamine-dependent GCN2 signaling in stromal cells promotes tumor growth and the development of the immunosuppressive tumor microenvironment, and that the PBT anti-tumor effect is mediated, at least in part, by targeting GCN2. Full article
(This article belongs to the Special Issue The Role of Polyamines in Human Health and Disease)
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15 pages, 1590 KiB  
Article
Whole Blood Spermine/Spermidine Ratio as a New Indicator of Sarcopenia Status in Older Adults
by Hidenori Sanayama, Kiyonori Ito, Susumu Ookawara, Takeshi Uemura, Yoshio Sakiyama, Hitoshi Sugawara, Kaoru Tabei, Kazuei Igarashi and Kuniyasu Soda
Biomedicines 2023, 11(5), 1403; https://doi.org/10.3390/biomedicines11051403 - 9 May 2023
Cited by 7 | Viewed by 1940
Abstract
Early diagnosis and therapeutic intervention improve the quality of life and prognosis of patients with sarcopenia. The natural polyamines spermine and spermidine are involved in many physiological activities. Therefore, we investigated blood polyamine levels as a potential biomarker for sarcopenia. Subjects were Japanese [...] Read more.
Early diagnosis and therapeutic intervention improve the quality of life and prognosis of patients with sarcopenia. The natural polyamines spermine and spermidine are involved in many physiological activities. Therefore, we investigated blood polyamine levels as a potential biomarker for sarcopenia. Subjects were Japanese patients >70 years of age who visited outpatient clinics or resided in nursing homes. Sarcopenia was determined based on muscle mass, muscle strength, and physical performance according to the criteria of the Asian Working Group for Sarcopenia (2019). The analysis included 182 patients (male: 38%, age: 83 [76–90] years). Spermidine levels were higher (p = 0.002) and the spermine/spermidine ratio was lower (p < 0.001) in the sarcopenia group than in the non-sarcopenia group. Polyamine concentration analysis showed that the odds ratios for age and spermidine changed in parallel with sarcopenia progression, and the odds ratio for the spermine/spermidine ratio changed inversely with the degree of sarcopenia progression. Additionally, when the odds ratio was analyzed with spermine/spermidine instead of polyamine concentrations, only for spermine/spermidine, the odds ratio values varied in parallel with the progression of sarcopenia. Based on the present data, we believe that the blood spermine/spermidine ratio may be a diagnostic indicator of risk for sarcopenia. Full article
(This article belongs to the Special Issue The Role of Polyamines in Human Health and Disease)
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14 pages, 1053 KiB  
Article
N-Carbamoylputrescine Amidohydrolase of Bacteroides thetaiotaomicron, a Dominant Species of the Human Gut Microbiota
by Hiromi Shimokawa, Mikiyasu Sakanaka, Yuki Fujisawa, Hirokazu Ohta, Yuta Sugiyama and Shin Kurihara
Biomedicines 2023, 11(4), 1123; https://doi.org/10.3390/biomedicines11041123 - 7 Apr 2023
Cited by 5 | Viewed by 2120
Abstract
Polyamines are bioactive amines that play a variety of roles, such as promoting cell proliferation and protein synthesis, and the intestinal lumen contains up to several mM polyamines derived from the gut microbiota. In the present study, we conducted genetic and biochemical analyses [...] Read more.
Polyamines are bioactive amines that play a variety of roles, such as promoting cell proliferation and protein synthesis, and the intestinal lumen contains up to several mM polyamines derived from the gut microbiota. In the present study, we conducted genetic and biochemical analyses of the polyamine biosynthetic enzyme N-carbamoylputrescine amidohydrolase (NCPAH) that converts N-carbamoylputrescine to putrescine, a precursor of spermidine in Bacteroides thetaiotaomicron, which is one of the most dominant species in the human gut microbiota. First, ncpah gene deletion and complemented strains were generated, and the intracellular polyamines of these strains cultured in a polyamine-free minimal medium were analyzed using high-performance liquid chromatography. The results showed that spermidine detected in the parental and complemented strains was depleted in the gene deletion strain. Next, purified NCPAH-(His)6 was analyzed for enzymatic activity and found to be capable of converting N-carbamoylputrescine to putrescine, with a Michaelis constant (Km) and turnover number (kcat) of 730 µM and 0.8 s−1, respectively. Furthermore, the NCPAH activity was strongly (>80%) inhibited by agmatine and spermidine, and moderately (≈50%) inhibited by putrescine. This feedback inhibition regulates the reaction catalyzed by NCPAH and may play a role in intracellular polyamine homeostasis in B. thetaiotaomicron. Full article
(This article belongs to the Special Issue The Role of Polyamines in Human Health and Disease)
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11 pages, 2174 KiB  
Brief Report
Changes in the Localization of Polyamine Spermidine in the Rat Retina with Age
by David S. Ríos, Christian J. Malpica-Nieves, Amanda Díaz-García, Misty J. Eaton and Serguei N. Skatchkov
Biomedicines 2023, 11(4), 1008; https://doi.org/10.3390/biomedicines11041008 - 24 Mar 2023
Cited by 2 | Viewed by 1584
Abstract
Polyamines (PAs) in the nervous system has a key role in regeneration and aging. Therefore, we investigated age-related changes in the expression of PA spermidine (SPD) in the rat retina. Fluorescent immunocytochemistry was used to evaluate the accumulation of SPD in retinae from [...] Read more.
Polyamines (PAs) in the nervous system has a key role in regeneration and aging. Therefore, we investigated age-related changes in the expression of PA spermidine (SPD) in the rat retina. Fluorescent immunocytochemistry was used to evaluate the accumulation of SPD in retinae from rats of postnatal days 3, 21, and 120. Glial cells were identified using glutamine synthetase (GS), whereas DAPI, a marker of cell nuclei, was used to differentiate between retinal layers. SPD localization in the retina was strikingly different between neonates and adults. In the neonatal retina (postnatal day 3-P3), SPD is strongly expressed in practically all cell types, including radial glia and neurons. SPD staining showed strong co-localization with the glial marker GS in Müller Cells (MCs) in the outer neuroblast layer. In the weaning period (postnatal day 21-P21), the SPD label was strongly expressed in all MCs, but not in neurons. In early adulthood (postnatal day 120-P120), SPD was localized in MCs only and was co-localized with the glial marker GS. A decline in the expression of PAs in neurons was observed with age while glial cells accumulated SPD after the differentiation stage (P21) and during aging in MC cellular endfoot compartments. Full article
(This article belongs to the Special Issue The Role of Polyamines in Human Health and Disease)
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