bims-polyam 2023-05-21 papers

bims-polyam

Biomed News

on Polyamines

Issue of 2023–05–21
seven papers selected by
Sebastian J. Hofer, University of Graz

N-Carbamoylputrescine Amidohydrolase of Bacteroides thetaiotaomicron, a Dominant Species of the Human Gut Microbiota.
Changes in the Localization of Polyamine Spermidine in the Rat Retina with Age.
Role of Polyamines in the Response to Salt Stress of Tomato.
Transcriptome Analysis of Redox Systems and Polyamine Metabolic Pathway in Hepatoma and Non-Tumor Hepatocyte-like Cells.
Acrolein produced during acute kidney injury promotes tubular cell death.
TGase-induced Cd tolerance by boosting polyamine, nitric oxide, cell wall composition and phytochelatin synthesis in tomato.
Polyamine metabolism patterns characterized tumor microenvironment, prognosis, and response to immunotherapy in colorectal cancer.

Biomedicines. 2023 Apr 07. pii: 1123. [Epub ahead of print]11(4):

N-Carbamoylputrescine Amidohydrolase of Bacteroides thetaiotaomicron, a Dominant Species of the Human Gut Microbiota.

Hiromi Shimokawa, Mikiyasu Sakanaka, Yuki Fujisawa, Hirokazu Ohta, Yuta Sugiyama, Shin Kurihara.

  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.

Keywords:  Bacteroides thetaiotaomicron; N-carbamoylputrescine amidohydrolase; agmatine; human gut microbiota; polyamine; putrescine; spermidine

DOI:  https://doi.org/10.3390/biomedicines11041123
Biomedicines. 2023 Mar 24. pii: 1008. [Epub ahead of print]11(4):

Changes in the Localization of Polyamine Spermidine in the Rat Retina with Age.

David S Ríos, Christian J Malpica-Nieves, Amanda Díaz-García, Misty J Eaton, Serguei N Skatchkov.

  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.

Keywords:  glial cell compartments; glial cells; nervous system; neurons; polyamines; retina; spermidine

DOI:  https://doi.org/10.3390/biomedicines11041008
Plants (Basel). 2023 Apr 30. pii: 1855. [Epub ahead of print]12(9):

Role of Polyamines in the Response to Salt Stress of Tomato.

Ilaria Borromeo, Fabio Domenici, Maddalena Del Gallo, Cinzia Forni.

  Plants irrigated with saline solutions undergo osmotic and oxidative stresses, which affect their growth, photosynthetic activity and yield. Therefore, the use of saline water for irrigation, in addition to the increasing soil salinity, is one of the major threats to crop productivity worldwide. Plant tolerance to stressful conditions can be improved using different strategies, i.e., seed priming and acclimation, which elicit morphological and biochemical responses to overcome stress. In this work, we evaluated the combined effect of priming and acclimation on salt stress response of a tomato cultivar (Solanum lycopersicum L.), very sensitive to salinity. Chemical priming of seeds was performed by treating seeds with polyamines (PAs): 2.5 mM putrescine (PUT), 2.5 mM spermine (SPM) and 2.5 mM spermidine (SPD). Germinated seeds of primed and non-primed (controls) were sown in non-saline soil. The acclimation consisted of irrigating the seedlings for 2 weeks with tap water, followed by irrigation with saline and non-saline water for 4 weeks. At the end of the growth period, morphological, physiological and biochemical parameters were determined. The positive effects of combined treatments were evident, when primed plants were compared to non-primed, grown under the same conditions. Priming with PAs improved tolerance to salt stress, reduced the negative effects of salinity on growth, improved membrane integrity, and increased photosynthetic pigments, proline and enzymatic and non-enzymatic antioxidant responses in all salt-exposed plants. These results may open new perspectives and strategies to increase tolerance to salt stress in sensitive species, such as tomato.

Keywords:  acclimation; polyamines; saline water; seed priming; tomato

DOI:  https://doi.org/10.3390/plants12091855
Biomolecules. 2023 Apr 21. pii: 714. [Epub ahead of print]13(4):

Transcriptome Analysis of Redox Systems and Polyamine Metabolic Pathway in Hepatoma and Non-Tumor Hepatocyte-like Cells.

Olga N Ivanova, George S Krasnov, Anastasiya V Snezhkina, Anna V Kudryavtseva, Vyacheslav S Fedorov, Natalia F Zakirova, Michail V Golikov, Sergey N Kochetkov, Birke Bartosch, Vladimir T Valuev-Elliston, Alexander V Ivanov.

  Reactive oxygen species (ROS) play a major role in the regulation of various processes in the cell. The increase in their production is a factor contributing to the development of numerous pathologies, including inflammation, fibrosis, and cancer. Accordingly, the study of ROS production and neutralization, as well as redox-dependent processes and the post-translational modifications of proteins, is warranted. Here, we present a transcriptomic analysis of the gene expression of various redox systems and related metabolic processes, such as polyamine and proline metabolism and the urea cycle in Huh7.5 hepatoma cells and the HepaRG liver progenitor cell line, that are widely used in hepatitis research. In addition, changes in response to the activation of polyamine catabolism that contribute to oxidative stress were studied. In particular, differences in the gene expression of various ROS-producing and ROS-neutralizing proteins, the enzymes of polyamine metabolisms and proline and urea cycles, as well as calcium ion transporters between cell lines, are shown. The data obtained are important for understanding the redox biology of viral hepatitis and elucidating the influence of the laboratory models used.

Keywords:  HepaRG; antioxidant enzymes; polyamines; proline metabolism; reactive oxygen species; urea cycle

DOI:  https://doi.org/10.3390/biom13040714
Biochem Biophys Res Commun. 2023 May 09. pii: S0006-291X(23)00585-5. [Epub ahead of print]666 137-145

Acrolein produced during acute kidney injury promotes tubular cell death.

Seishi Aihara, Kumiko Torisu, Yutaro Hirashima, Takanari Kitazono, Toshiaki Nakano.

  Acute kidney injury is an important global health concern as it is associated with high morbidity and mortality. Polyamines, essential for cell growth and proliferation, are known to inhibit cardiovascular disease. However, under conditions of cellular damage, toxic acrolein is produced from polyamines by the enzyme spermine oxidase (SMOX). We used a mouse renal ischemia-reperfusion model and human proximal tubule cells (HK-2) to investigate whether acrolein exacerbates acute kidney injury by renal tubular cell death. Acrolein visualized by acroleinRED was increased in ischemia-reperfusion kidneys, particularly in tubular cells. When HK-2 cells were cultured under 1% oxygen for 24 h, then switched to 21% oxygen for 24 h (hypoxia-reoxygenation), acrolein accumulated and SMOX mRNA and protein levels were increased. Acrolein induced cell death and fibrosis-related TGFB1 mRNA in HK-2 cells. Administration of the acrolein scavenger cysteamine suppressed the acrolein-induced upregulation of TGFB1 mRNA. Cysteamine also inhibited a decrease in the mitochondrial membrane potential observed by MitoTrackerCMXRos, and cell death induced by hypoxia-reoxygenation. The siRNA-mediated knockdown of SMOX also suppressed hypoxia-reoxygenation-induced acrolein accumulation and cell death. Our study suggests that acrolein exacerbates acute kidney injury by promoting tubular cell death during ischemia-reperfusion injury. Treatment to control the accumulation of acrolein might be an effective therapeutic option for renal ischemia-reperfusion injury.

Keywords:  Acrolein; Acute kidney injury; Ischemia-reperfusion injury; Polyamine; Renal tubular cell; Spermine oxidase

DOI:  https://doi.org/10.1016/j.bbrc.2023.05.029
Ecotoxicol Environ Saf. 2023 May 16. pii: S0147-6513(23)00527-4. [Epub ahead of print]259 115023

TGase-induced Cd tolerance by boosting polyamine, nitric oxide, cell wall composition and phytochelatin synthesis in tomato.

Min Zhong, Lingqi Yue, Hongyi Qin, Guohu Wang, Liwen Xiao, Qinqin Cheng, Bingfu Lei, Riming Huang, Xian Yang, Yunyan Kang.

  In highly intensive greenhouse vegetable production, soil acidification was caused by excessive fertilization, increasing cadmium (Cd) concentrations in the vegetables, which bears environmental hazards and is a negative influence on vegetables and humans. Transglutaminases (TGases), a central mediator for certain physiological effects of polyamines (PAs) in the plant kingdom, play important roles in plant development and stress response. Despite increased research on the crucial role of TGase in protecting against environmental stresses, relatively little is known about the mechanisms of Cd tolerance. In this study, we found, TGase activity and transcript level, which was upregulated by Cd, and TGase-induced Cd tolerance related to endogenous bound PAs increase and formation of nitric oxide (NO). Plant growth of tgase mutants was hypersensitive to Cd, chemical complementation by putrescine, sodium nitroprusside (SNP, nitric oxide donor) or gain of function TGase experiments restore Cd tolerance. α-diflouromethylornithine (DFMO, a selective ODC inhibitor) and 2-4-carboxyphenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (cPTIO, NO scavenger), were respectively found declined drastically endogenous bound PA and NO content in TGase overexpression plants. Likewise, we reported that TGase interacted with polyamine uptake protein 3 (Put3), and the silencing of Put3 largely reduced TGase-induced Cd tolerance and bound PAs formation. This salvage strategy depends on TGase-regulated synthesis of bound PAs and NO that is able to positively increase the concentration of thiol and phytochelatins, elevate Cd in the cell wall, as well as induce the levels of expression Cd uptake and transport genes. Collectively, these findings indicate that TGase-mediated enhanced levels of bound PA and NO acts as a vital mechanism to protect the plant from Cd-caused toxicity.

Keywords:  Cd stress; Cell wall; Nitric oxide; Phytochelatin; Polyamines; TGase

DOI:  https://doi.org/10.1016/j.ecoenv.2023.115023
Cancer Cell Int. 2023 May 18. 23(1): 96

Polyamine metabolism patterns characterized tumor microenvironment, prognosis, and response to immunotherapy in colorectal cancer.

Enkui Zhang, Chengsheng Ding, Shuchun Li, Batuer Aikemu, Xueliang Zhou, Xiaodong Fan, Jing Sun, Xiao Yang, Minhua Zheng.

   BACKGROUND: Changes in Polyamine metabolism (PAM) have been shown to establish a suppressive tumor microenvironment (TME) and substantially influence the progression of cancer in the recent studies. However, newly emerging data have still been unable to fully illuminate the specific effects of PAM in human cancers. Here, we analyzed the expression profiles and clinical relevance of PAM genes in colorectal cancer (CRC).
METHODS: Based on unsupervised consensus clustering and principal component analysis (PCA) algorithm, we designed a scoring model to evaluate the prognosis of CRC patients and characterize the TME immune profiles, with related independent immunohistochemical validation cohort. Through comparative profiling of cell communities defined by single cell sequencing data, we identified the distinct characteristics of polyamine metabolism in the TME of CRC.
RESULTS: Three PAM patterns with distinct prognosis and TME features were recognized from 1224 CRC samples. Moreover, CRC patients could be divided into high- and low-PAMscore subgroups by PCA-based scoring system. High PAMscore subgroup were associated to more advanced stage, higher infiltration level of immunosuppressive cells, and unfavorable prognosis. These results were also validated in CRC samples from other public CRC datasets and our own cohort, which suggested PAM genes were ideal biomarkers for predicting CRC prognosis. Notably, PAMscore also corelated with microsatellite instability-high (MSI-H) status, higher tumor mutational burden (TMB), and increased immune checkpoint gene expression, implying a potential role of PAM genes in regulating response to immunotherapy. To further confirm above results, we demonstrated a high-resolution landscape of TME and cell-cell communication network in different PAM patterns using single cell sequencing data and found that polyamine metabolism affected the communication between cancer cells and several immune cells such as T cells, B cells and myeloid cells.
CONCLUSION: In total, our findings highlighted the significance of polyamine metabolism in shaping the TME and predicting the prognosis of CRC patients, providing novel strategies for immunotherapy and the targeting polyamine metabolites.

Keywords:  Colorectal cancer; Immunotherapy; Polyamine metabolism; Prediction; Tumor microenvironment

DOI:  https://doi.org/10.1186/s12935-023-02892-z