Papers - UEMURA Takeshi
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Polyamine transport is mediated by both endocytic and solute carrier transport mechanisms in the gastrointestinal tract Reviewed
Takeshi Uemura, David E. Stringer, Karen A. Blohm-Mangone, Eugene W. Gerner
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY 299 ( 2 ) G517 - G522 2010.08
Language：English Publishing type：Research paper (scientific journal)
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Polyamine modulon in yeast-Stimulation of COX4 synthesis by spermidine at the level of translation Reviewed
Takeshi Uemura, Kyohei Higashi, Miki Takigawa, Toshihiko Toida, Keiko Kashiwagi, Kazuei Igarashi
INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY 41 ( 12 ) 2538 - 2545 2009.12
Language：English Publishing type：Research paper (scientific journal)
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Identification and characterization of a diamine exporter in colon epithelial cells Reviewed
Takeshi Uemura, Hagit F. Yerushalmi, George Tsaprailis, David E. Stringer, Kirk E. Pastorian, Leo Hawel, Craig V. Byus, Eugene W. Gerner
JOURNAL OF BIOLOGICAL CHEMISTRY 283 ( 39 ) 26428 - 26435 2008.09
Language：English Publishing type：Research paper (scientific journal)
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Identification of a spermidine excretion protein complex (MdtJl) in Escherichia coli Reviewed
Kyohei Higashi, Hiroyuki Ishigure, Risa Demizu, Takeshi Uemura, Kunihiko Nishino, Akihito Yamaguchi, Keiko Kashiwagi, Kazuei Igarashil
JOURNAL OF BACTERIOLOGY 190 ( 3 ) 872 - 878 2008.02
Language：English Publishing type：Research paper (scientific journal)
DOI： 10.1128/JB.01505-07
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Polyamine uptake by DUR3 and SAM3 in Saccharomyces cerevisiae Reviewed
Takeshi Uemura, Keiko Kashiwagi, Kazuei Igarashi
JOURNAL OF BIOLOGICAL CHEMISTRY 282 ( 10 ) 7733 - 7741 2007.03
Language：English Publishing type：Research paper (scientific journal)
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Identification of the cadaverine recognition site on the cadaverine-lysine antiporter CadB Reviewed
Waraporn Soksawatmaekhin, Takeshi Uemura, Natsuko Fukiwake, Keiko Kashiwagi, Kazuei Igarashi
JOURNAL OF BIOLOGICAL CHEMISTRY 281 ( 39 ) 29213 - 29220 2006.09
Language：English Publishing type：Research paper (scientific journal)
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Excretion of putrescine and spermidine by the protein encoded by YKL174c (TPO5) in Saccharomyces cerevisiae Reviewed
K Tachihara, T Uemura, K Kashiwagi, K Igarashi
JOURNAL OF BIOLOGICAL CHEMISTRY 280 ( 13 ) 12637 - 12642 2005.04
Language：English Publishing type：Research paper (scientific journal)
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Uptake of putrescine and spermidine by Gap1p on the plasma membrane in Saccharomyces cerevisiae Reviewed
T Uemura, K Kashiwagi, K Igarashi
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 328 ( 4 ) 1028 - 1033 2005.03
Language：English Publishing type：Research paper (scientific journal)
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Characteristics of the polyamine transporter TPO1 and regulation of its activity and cellular localization by phosphorylation Reviewed
T Uemura, K Tachihara, H Tomitori, K Kashiwagi, K Igarashi
JOURNAL OF BIOLOGICAL CHEMISTRY 280 ( 10 ) 9646 - 9652 2005.03
Language：English Publishing type：Research paper (scientific journal)
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Uptake of GABA and putrescine by UGA4 on the vacuolar membrane in Saccharomyces cerevisiae Reviewed
T Uemura, Y Tomonari, K Kashiwagi, K Igarashi
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 315 ( 4 ) 1082 - 1087 2004.03
Language：English Publishing type：Research paper (scientific journal)
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Intestinal luminal polyamines support the gut colonization of enteric bacterial pathogens by modulating flagellar motility and nitrate respiration. International journal
Tsuyoshi Miki, Shin Kurihara, Takeshi Uemura, Yuta Ami, Masahiro Ito, Takeshi Haneda, Takemitsu Furuchi, Nobuhiko Okada, Tohru Minamino, Yun-Gi Kim
mBio 16 ( 9 ) e0178625 2025.09
Language：English Publishing type：Research paper (scientific journal)
UNLABELLED: Salmonella enterica serovar Typhimurium (STm) is an etiological agent of common foodborne diseases and a major health concern worldwide. STm gastrointestinal infection induces intestinal inflammation, allowing STm outgrowth in the gut lumen by exploiting inflammation-induced host factors. Polyamines, including putrescine and spermidine, are crucial for both intestinal homeostasis and STm infectivity. However, our understanding of polyamines' role in STm infection remains incomplete. This study aimed to elucidate that role. We found that defects in polyamine uptake‒dependent homeostasis altered the expression profiles of genes involved in STm flagellar motility and nitrate respiration. Spermidine supplementation restored the expression of the nar and nap operons, which encode distinct nitrate reductases, in an STm mutant with impaired polyamine homeostasis. Thus, the polyamine homeostasis-defective STm mutant exhibited reduced nitrate respiration, which spermidine supplementation rescued. In contrast, both putrescine and spermidine partially reversed the impaired expression of flagellin in this mutant. Additionally, the mutant exhibited a higher proportion of nonmotile cells compared with the wild-type strain. Finally, we demonstrated that the reduced gut colonization of this mutant was due to decreased nitrate respiration and flagellar motility. Moreover, polyamine supplementation enhanced the luminal growth of STm and a pathobiont, Escherichia coli. Our findings reveal that intestinal luminal polyamines support the growth of enteric bacterial pathogens in the intestinal tract. IMPORTANCE: Microbiota-derived metabolites play crucial roles in gastrointestinal infections caused by enteric pathogens. One notable example is short-chain fatty acids, such as acetate, propionate, and butyrate, which are beneficial for health and protective against infection. This study highlights that the gut microbiota‒derived polyamine spermidine drives luminal growth of enteric bacterial pathogens. The findings suggest that higher luminal levels of polyamines may be a risk factor for enteric infections. Therefore, regulating luminal polyamines could represent a promising therapeutic intervention for gastrointestinal infections.
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NF-E2-related factor 1 suppresses the expression of a spermine oxidase and the production of highly reactive acrolein. International journal
Tomoaki Hirakawa, Megumi Taniuchi, Yoko Iguchi, Sudarma Bogahawaththa, Kiko Yoshitake, Shanika Werellagama, Takeshi Uemura, Tadayuki Tsujita
Scientific reports 15 ( 1 ) 12405 - 12405 2025.04
Language：English Publishing type：Research paper (scientific journal)
Polyamines (putrescine, spermidine, and spermine) are among the most abundant intracellular small molecular metabolites, with concentrations at the mM level. The ratios of these three molecules remain constant under physiological conditions. Stress (i.e. polyamine overload, oxidative stress, aging, infection, etc.) triggers the catabolic conversion of spermine to spermidine, ultimately yielding acrolein and hydrogen peroxide. The potential of acrolein to induce DNA damage and protein denaturation is 1,000 times greater than that of reactive oxygen species. We have shown that these polyamine metabolic pathways also involve the nuclear factor erythroid-2-related factor 1 (NRF1) transcription factor. In our chemically-inducible, liver-specific Nrf1-knockout mice, the polyamine catabolic pathway dominated the anabolic pathway, producing free acrolein and accumulating acrolein-conjugated proteins in vivo. This metabolic feature implicates SMOX as an important causative enzyme. Chromatin immunoprecipitation and reporter assays confirmed that NRF1 directly suppressed Smox expression. This effect was also observed in vitro. Ectopic overexpression of SMOX increased the accumulation of free acrolein and acrolein-conjugated proteins. SMOX knockdown reversed the accumulation of free acrolein and acrolein-conjugated proteins. Our results show that NRF1 typically suppresses Smox expression when NRF1 is downregulated, SMOX is upregulated, and polyamine metabolic pathways are altered, producing low molecular weight polyamines and acrolein.
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Polyamines enhance repeat-associated non-AUG translation from CCUG repeats by stabilizing the tertiary structure of RNA. International journal
Akihiro Oguro, Takeshi Uemura, Kodai Machida, Kanta Kitajiri, Ayasa Tajima, Takemitsu Furuchi, Gota Kawai, Hiroaki Imataka
The Journal of biological chemistry 301 ( 3 ) 108251 - 108251 2025.03
Language：English Publishing type：Research paper (scientific journal)
Repeat expansion disorders are caused by abnormal expansion of microsatellite repeats. Repeat-associated non-AUG (RAN) translation is one of the pathogenic mechanisms underlying repeat expansion disorders, but the exact molecular mechanism underlying RAN translation remains unclear. Polyamines are ubiquitous biogenic amines that are essential for cell proliferation and cellular functions. They are predominantly found in cells in complexes with RNA and influence many cellular events, but the relationship between polyamines and RAN translation is yet to be explored. Here, we show that, in both a cell-free protein synthesis system and cell culture, polyamines promote RAN translation of RNA-containing CCUG repeats. The CCUG-dependent RAN translation is suppressed when cells are depleted of polyamines but can be recovered by the addition of polyamines. Thermal stability analysis revealed that the tertiary structure of the CCUG-repeat RNA is stabilized by the polyamines. Spermine was the most effective polyamine for stabilizing CCUG-repeat RNA and enhancing RAN translation. These results suggest that polyamines, particularly spermine, modulate RAN translation of CCUG-repeat RNA by stabilizing the tertiary structure of the repeat RNA.
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Special Issue "Polyamines in Aging and Disease". International journal
Takeshi Uemura, Yusuke Terui
International journal of molecular sciences 25 ( 22 ) 2024.11
Language：English Publishing type：Research paper (scientific journal)
Polyamines are bioactive amines found in almost all living organisms and are essential for normal cellular functions [...].
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Salmonella Typhimurium exploits host polyamines for assembly of the type 3 secretion machinery. International journal
Tsuyoshi Miki, Takeshi Uemura, Miki Kinoshita, Yuta Ami, Masahiro Ito, Nobuhiko Okada, Takemitsu Furuchi, Shin Kurihara, Takeshi Haneda, Tohru Minamino, Yun-Gi Kim
PLoS biology 22 ( 8 ) e3002731 2024.08
Language：English Publishing type：Research paper (scientific journal)
Bacterial pathogens utilize the factors of their hosts to infect them, but which factors they exploit remain poorly defined. Here, we show that a pathogenic Salmonella enterica serovar Typhimurium (STm) exploits host polyamines for the functional expression of virulence factors. An STm mutant strain lacking principal genes required for polyamine synthesis and transport exhibited impaired infectivity in mice. A polyamine uptake-impaired strain of STm was unable to inject effectors of the type 3 secretion system into host cells due to a failure of needle assembly. STm infection stimulated host polyamine production by increasing arginase expression. The decline in polyamine levels caused by difluoromethylornithine, which inhibits host polyamine production, attenuated STm colonization, whereas polyamine supplementation augmented STm pathogenesis. Our work reveals that host polyamines are a key factor promoting STm infection, and therefore a promising therapeutic target for bacterial infection.
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Caldomycin, a new guanidopolyamine produced by a novel agmatine homocoupling enzyme involved in homospermidine biosynthesis. International journal
Teruyuki Kobayashi, Akihiko Sakamoto, Tamao Hisano, Keiko Kashiwagi, Kazuei Igarashi, Koichi Takao, Takeshi Uemura, Takemitsu Furuchi, Yoshiaki Sugita, Toshiyuki Moriya, Tairo Oshima, Yusuke Terui
Scientific reports 14 ( 1 ) 7566 - 7566 2024.03
Language：English Publishing type：Research paper (scientific journal)
An extreme thermophilic bacterium, Thermus thermophilus produces more than 20 unusual polyamines, but their biosynthetic pathways, including homospermidine, are not yet fully understood. Two types of homospermidine synthases have been identified in plants and bacteria, which use spermidine and putrescine or two molecules of putrescine as substrates. However, homospermidine synthases with such substrate specificity have not been identified in T. thermophilus. Here we identified a novel agmatine homocoupling enzyme that is involved in homospermidine biosynthesis in T. thermophilus. The reaction mechanism is different from that of a previously described homospermidine synthase, and involves conjugation of two molecules of agmatine, which produces a diamidino derivative of homospermidine (caldomycin) as an immediate precursor of homospermidine. We conclude that there is a homospermidine biosynthetic pathway from agmatine via caldomycin synthase followed by ureohydrolase in T. thermophilus. Furthermore, it is shown that caldomycin is a novel compound existing in nature.
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Inhibition of Polyamine Catabolism Reduces Cellular Senescence. International journal
Takeshi Uemura, Miki Matsunaga, Yuka Yokota, Koichi Takao, Takemitsu Furuchi
International journal of molecular sciences 24 ( 17 ) 2023.08
Language：English Publishing type：Research paper (scientific journal)
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.
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Whole Blood Spermine/Spermidine Ratio as a New Indicator of Sarcopenia Status in Older Adults. International journal
Hidenori Sanayama, Kiyonori Ito, Susumu Ookawara, Takeshi Uemura, Yoshio Sakiyama, Hitoshi Sugawara, Kaoru Tabei, Kazuei Igarashi, Kuniyasu Soda
Biomedicines 11 ( 5 ) 2023.05
Language：English Publishing type：Research paper (scientific journal)
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.
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Putrescine Biosynthesis from Agmatine by Arginase (TtARG) in Thermus thermophilus. International journal
Teruyuki Kobayashi, Akihiko Sakamoto, Keiko Kashiwagi, Kazuei Igarashi, Koichi Takao, Takeshi Uemura, Toshiyuki Moriya, Tairo Oshima, Yusuke Terui
Journal of biochemistry 2023.03
Language：English Publishing type：Research paper (scientific journal)
In the three domains of life, three biosynthetic pathways are known for putrescine. The first route is conversion of ornithine to putrescine by ornithine decarboxylase (ODC: SpeC), the second route is the conversion of arginine to agmatine by arginine decarboxylase (ADC: SpeA), followed by the conversion of agmatine to putrescine by agmatine ureohydrolase (AUH: SpeB), and the third route is the conversion of agmatine to N-carbamoylputrescine by agmatine deiminase (agmatine iminohydrolase, AIH), followed by the conversion of N-carbamoylputrescine to putrescine by N-carbamoylputrescine amidohydrolase (NCPAH). An extreme thermophile, Thermus thermophilus produces putrescine, although this bacterium lacks homologs for putrescine synthesizing pathways such as ODC, AUH, AIH and NCPAH. To identify genes involved in putrescine biosynthesis in T. thermophilus, putrescine biosynthesis was examined by disruption of a predicted gene for agmatinase (agmatine ureohydrolase), or by using purified enzyme. It was found that arginase (TTHA1496) showed an agmatinase activity utilizing agmatine as a substrate. These results indicate that this bacterium can use arginase for putrescine biosynthesis. Arginase is a major contributor to putrescine biosynthesis under physiological conditions. The presence of an alternative pathway for converting agmatine into putrescine is functionally important for polyamine metabolism supporting survival at extreme environments.
DOI： 10.1093/jb/mvad026
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Positive Correlation between Relative Concentration of Spermine to Spermidine in Whole Blood and Skeletal Muscle Mass Index: A Possible Indicator of Sarcopenia and Prognosis of Hemodialysis Patients. International journal
Hidenori Sanayama, Kiyonori Ito, Susumu Ookawara, Takeshi Uemura, Sojiro Imai, Satoshi Kiryu, Miho Iguchi, Yoshio Sakiyama, Hitoshi Sugawara, Yoshiyuki Morishita, Kaoru Tabei, Kazuei Igarashi, Kuniyasu Soda
Biomedicines 11 ( 3 ) 2023.03
Language：English Publishing type：Research paper (scientific journal)
Several mechanisms strictly regulate polyamine concentration, and blood polyamines are excreted in urine. This indicates polyamine accumulation in renal dysfunction, and studies have shown increased blood polyamine concentrations in patients with renal failure. Hemodialysis (HD) may compensate for polyamine excretion; however, little is known about polyamine excretion. We measured whole-blood polyamine levels in patients on HD and examined the relationship between polyamine concentrations and indicators associated with health status. Study participants were 59 hemodialysis patients (median age: 70.0 years) at Minami-Uonuma City Hospital and 26 healthy volunteers (median age: 44.5 years). Whole-blood spermidine levels were higher and spermine/spermidine ratio (SPM/SPD) was lower in hemodialysis patients. Hemodialysis showed SPD efflux into the dialysate; however, blood polyamine levels were not altered by hemodialysis and appeared to be minimally excreted. The skeletal muscle mass index (SMI), which was positively correlated with hand grip strength and serum albumin level, was positively correlated with SPM/SPD. Given that sarcopenia and low serum albumin levels are reported risk factors for poor prognosis in HD patients, whole blood SPM/SPD in hemodialysis patients may be a new indicator of the prognosis and health status of HD patients.