bims-polyam Biomed News
on Polyamines
Issue of 2022‒07‒31
eight papers selected by
Sebastian J. Hofer
University of Graz
  1. The Involvement of Polyamines Catabolism in the Crosstalk between Neurons and Astrocytes in Neurodegeneration.
  2. Polyamines and Their Metabolism: From the Maintenance of Physiological Homeostasis to the Mediation of Disease.
  3. Research Progress and Potential Applications of Spermidine in Ocular Diseases.
  4. Ornithine Decarboxylase in Gastric Epithelial Cells Promotes the Immunopathogenesis of Helicobacter pylori Infection.
  5. Polyamine Oxidase Expression Is Downregulated by 17β-Estradiol via Estrogen Receptor 2 in Human MCF-7 Breast Cancer Cells.
  6. Roles of lncRNA LVBU in regulating urea cycle/polyamine synthesis axis to promote colorectal carcinoma progression.
  7. Eukaryotic Translation Initiation Factor 5A Independently Predicts Poor Prognosis of Cholangiocarcinoma Patients and Regulates the Ferroptosis and Mitochondrial Apoptosis.
  8. Temporal patterns of increased growth hormone secretion in mice after oral administration of L-ornithine: possible involvement of ghrelin receptors.
  1. Biomedicines. 2022 Jul 21. pii: 1756. [Epub ahead of print]10(7):
    The Involvement of Polyamines Catabolism in the Crosstalk between Neurons and Astrocytes in Neurodegeneration.
    Manuela Cervelli, Monica Averna, Laura Vergani, Marco Pedrazzi, Sarah Amato, Cristian Fiorucci, Marianna Nicoletta Rossi, Guido Maura, Paolo Mariottini, Chiara Cervetto, Manuela Marcoli.
      In mammalian cells, the content of polyamines is tightly regulated. Polyamines, including spermine, spermidine and putrescine, are involved in many cellular processes. Spermine oxidase specifically oxidizes spermine, and its deregulated activity has been reported to be linked to brain pathologies involving neuron damage. Spermine is a neuromodulator of a number of ionotropic glutamate receptors and types of ion channels. In this respect, the Dach-SMOX mouse model overexpressing spermine oxidase in the neocortex neurons was revealed to be a model of chronic oxidative stress, excitotoxicity and neuronal damage. Reactive astrocytosis, chronic oxidative and excitotoxic stress, neuron loss and the susceptibility to seizure in the Dach-SMOX are discussed here. This genetic model would help researchers understand the linkage between polyamine dysregulation and neurodegeneration and unveil the roles of polyamines in the crosstalk between astrocytes and neurons in neuroprotection or neurodegeneration.
    Keywords:  mouse genetic model; neuron damage; polyamine; reactive astrocytosis; spermine oxidase
    DOI:  https://doi.org/10.3390/biomedicines10071756
  2. Med Sci (Basel). 2022 Jul 15. pii: 38. [Epub ahead of print]10(3):
    Polyamines and Their Metabolism: From the Maintenance of Physiological Homeostasis to the Mediation of Disease.
    Kamyar Zahedi, Sharon Barone, Manoocher Soleimani.
      The polyamines spermidine and spermine are positively charged aliphatic molecules. They are critical in the regulation of nucleic acid and protein structures, protein synthesis, protein and nucleic acid interactions, oxidative balance, and cell proliferation. Cellular polyamine levels are tightly controlled through their import, export, de novo synthesis, and catabolism. Enzymes and enzymatic cascades involved in polyamine metabolism have been well characterized. This knowledge has been used for the development of novel compounds for research and medical applications. Furthermore, studies have shown that disturbances in polyamine levels and their metabolic pathways, as a result of spontaneous mutations in patients, genetic engineering in mice or experimentally induced injuries in rodents, are associated with multiple maladaptive changes. The adverse effects of altered polyamine metabolism have also been demonstrated in in vitro models. These observations highlight the important role these molecules and their metabolism play in the maintenance of physiological normalcy and the mediation of injury. This review will attempt to cover the extensive and diverse knowledge of the biological role of polyamines and their metabolism in the maintenance of physiological homeostasis and the mediation of tissue injury.
    Keywords:  polyamine; polyamine metabolism; putrescine; spermidine; spermine
    DOI:  https://doi.org/10.3390/medsci10030038
  3. Pharmaceutics. 2022 Jul 19. pii: 1500. [Epub ahead of print]14(7):
    Research Progress and Potential Applications of Spermidine in Ocular Diseases.
    Wentao Han, Haoyu Li, Baihua Chen.
      Spermidine, a natural polyamine, exists in almost all human tissues, exhibiting broad properties like anti-aging, autophagy induction, anti-inflammation, anti-oxidation, cell proliferation activation, and ion channel regulation. Considering that spermidine is already present in human nutrition, recent studies targeting supplementing exogenous sources of this polyamine appear feasible. The protective role of spermidine in various systems has been illuminated in the literature, while recent progress of spermidine administration in ocular diseases remains to be clarified. This study shows the current landscape of studies on spermidine and its potential to become a promising therapeutic agent to treat ocular diseases: glaucoma, optic nerve injury, age-related macular degeneration (AMD), cataracts, dry eye syndrome, and bacterial keratitis. It also has the potential to become a potent biomarker to predict keratoconus (KC), cataracts, uveitis, glaucoma, proliferative diabetic retinopathy (PDR), proliferative vitreoretinopathy (PVR), and retinopathy of prematurity (ROP). We also summarize the routes of administration and the effects of spermidine at different doses.
    Keywords:  biomarker; eye; ocular diseases; spermidine; therapeutic agent
    DOI:  https://doi.org/10.3390/pharmaceutics14071500
  4. J Immunol. 2022 Jul 27. pii: ji2100795. [Epub ahead of print]
    Ornithine Decarboxylase in Gastric Epithelial Cells Promotes the Immunopathogenesis of Helicobacter pylori Infection.
    Yvonne L Latour, Johanna C Sierra, Kara M McNamara, Thaddeus M Smith, Paula B Luis, Claus Schneider, Alberto G Delgado, Daniel P Barry, Margaret M Allaman, M Wade Calcutt, Kevin L Schey, M Blanca Piazuelo, Alain P Gobert, Keith T Wilson.
      Colonization by Helicobacter pylori is associated with gastric diseases, ranging from superficial gastritis to more severe pathologies, including intestinal metaplasia and adenocarcinoma. The interplay of the host response and the pathogen affect the outcome of disease. One major component of the mucosal response to H. pylori is the activation of a strong but inefficient immune response that fails to control the infection and frequently causes tissue damage. We have shown that polyamines can regulate H. pylori-induced inflammation. Chemical inhibition of ornithine decarboxylase (ODC), which generates the polyamine putrescine from l-ornithine, reduces gastritis in mice and adenocarcinoma incidence in gerbils infected with H. pylori However, we have also demonstrated that Odc deletion in myeloid cells enhances M1 macrophage activation and gastritis. Here we used a genetic approach to assess the specific role of gastric epithelial ODC during H. pylori infection. Specific deletion of the gene encoding for ODC in gastric epithelial cells reduces gastritis, attenuates epithelial proliferation, alters the metabolome, and downregulates the expression of immune mediators induced by H. pylori Inhibition of ODC activity or ODC knockdown in human gastric epithelial cells dampens H. pylori-induced NF-κB activation, CXCL8 mRNA expression, and IL-8 production. Chronic inflammation is a major risk factor for the progression to more severe pathologies associated with H. pylori infection, and we now show that epithelial ODC plays an important role in mediating this inflammatory response.
    DOI:  https://doi.org/10.4049/jimmunol.2100795
  5. Int J Mol Sci. 2022 Jul 07. pii: 7521. [Epub ahead of print]23(14):
    Polyamine Oxidase Expression Is Downregulated by 17β-Estradiol via Estrogen Receptor 2 in Human MCF-7 Breast Cancer Cells.
    Jin Hyung Kim, Seung-Taek Lee.
      Polyamine levels decrease with menopause; however, little is known about the mechanisms regulated by menopause. In this study, we found that among the genes involved in the polyamine pathway, polyamine oxidase (PAOX) mRNA levels were the most significantly reduced by treatment with 17β-estradiol in estrogen receptor (ESR)-positive MCF-7 breast cancer cells. Treatment with 17β-estradiol also reduced the PAOX protein levels. Treatment with selective ESR antagonists and knockdown of ESR members revealed that estrogen receptor 2 (ESR2; also known as ERβ) was responsible for the repression of PAOX by 17β-estradiol. A luciferase reporter assay showed that 17β-estradiol downregulates PAOX promoter activity and that 17β-estradiol-dependent PAOX repression disappeared after deletions (-3126/-2730 and -1271/-1099 regions) or mutations of activator protein 1 (AP-1) binding sites in the PAOX promoter. Chromatin immunoprecipitation analysis showed that ESR2 interacts with AP-1 bound to each of the two AP-1 binding sites. These results demonstrate that 17β-estradiol represses PAOX transcription by the interaction of ESR2 with AP-1 bound to the PAOX promoter. This suggests that estrogen deficiency may upregulate PAOX expression and decrease polyamine levels.
    Keywords:  17β-estradiol (E2); activator protein 1 (AP-1); estrogen receptor (ESR); polyamine; polyamine oxidase (PAOX)
    DOI:  https://doi.org/10.3390/ijms23147521
  6. Oncogene. 2022 Jul 29.
    Roles of lncRNA LVBU in regulating urea cycle/polyamine synthesis axis to promote colorectal carcinoma progression.
    Xiangqi Meng, Jingxuan Peng, Xiaoshan Xie, Fenghai Yu, Wencong Wang, Qihao Pan, Huilin Jin, Xiaoling Huang, Hongyan Yu, Shengrong Li, Dianying Feng, Qingxin Liu, Lekun Fang, Mong-Hong Lee.
      Altered expression of Urea Cycle (UC) enzymes occurs in many tumors, resulting a metabolic hallmark termed as UC dysregulation. Polyamines are synthesized from ornithine, and polyamine synthetic genes are elevated in various tumors. However, the underlying deregulations of UC/ polyamine synthesis in cancer remain elusive. Here, we characterized a hypoxia-induced lncRNA LVBU (lncRNA regulation via BCL6/urea cycle) that is highly expressed in colorectal cancer (CRC) and correlates with poor cancer prognosis. Increased LVBU expression promoted CRC cells proliferation, foci formation and tumorigenesis. Further, LVBU regulates urea cycle and polyamine synthesis through BCL6, a negative regulator of p53. Mechanistically, overexpression of LVBU competitively bound miR-10a/miR-34c to protect BCL6 from miR-10a/34c-mediated degradation, which in turn allows BCL6 to block p53-mediated suppression of genes (arginase1 ARG1, ornithine transcarbamylase OTC, ornithine decarboxylase 1 ODC1) involved in UC/polyamine synthesis. Significantly, ODC1 inhibitor attenuated the growth of patient derived xenografts (PDX) that sustain high LVBU levels. Taken together, elevated LVBU can regulate BCL6-p53 signaling axis for systemic UC/polyamine synthesis reprogramming and confers a predilection toward CRC development. Our data demonstrates that further drug development and clinical evaluation of inhibiting UC/polyamine synthesis are warranted for CRC patients with high expression of LVBU.
    DOI:  https://doi.org/10.1038/s41388-022-02413-8
  7. J Oncol. 2022 ;2022 4250531
    Eukaryotic Translation Initiation Factor 5A Independently Predicts Poor Prognosis of Cholangiocarcinoma Patients and Regulates the Ferroptosis and Mitochondrial Apoptosis.
    Ping Wan, Taiyuan Li, Longfei Zhou, Jun Zhang, Xuefeng Rao.
      Cholangiocarcinoma (CCA) is a hepatobiliary carcinoma characterized by the differentiation of bile duct cells, and the patients with CCA often have a poor prognosis. Eukaryotic translation initiation factor 5A (eIF5A) is reported to have multiple biological activities. Targeted activation of ferroptosis may be a therapeutic strategy for cancer. Nevertheless, the effects of eIF5A and ferroptosis on CCA are still elucidated. Our study explored the effects of eIF5A in CCA, and the mechanisms also are studied. In this paper, TCGA database analysis suggested that eIF5A was upregulated in CCA, and high expression of eIF5A might predict a poor prognosis. Moreover, FANCD2, SLC7A11, and HSPB1 were significantly overexpressed in CCA. The results indicated that eIF5A was overexpressed in CCA tissues and cells. Further experiments demonstrated that eIF5A silencing decreased CCA cell activity and enhanced ferroptosis and mitochondrial apoptosis. In addition, upregulation of eIF5A showed the opposite effect on CCA cells compared with downregulation of eIF5A. Finally, the silencing of eIF5A could restrain the growth of xenografted tumors and promote ferroptosis. Overall, eIF5A enlarged CCA cell activity and attenuated ferroptosis and mitochondrial apoptosis. The results suggested that assessment of eIF5A might provide help for the diagnosis and treatment of CCA.
    DOI:  https://doi.org/10.1155/2022/4250531
  8. J Vet Med Sci. 2022 Jul 26.
    Temporal patterns of increased growth hormone secretion in mice after oral administration of L-ornithine: possible involvement of ghrelin receptors.
    Emi Taniguchi, Ayumi Hattori, Kaito Kurogi, Yukihiro Hishida, Fumiko Watanabe, Mitsuhiro Furuse, Shinobu Yasuo.
      l-Ornithine is known to stimulate growth hormone (GH) release in mammals. Here, we demonstrated that increases in plasma GH levels after oral administration of l-ornithine were first observed 150 min after administration, and the elevated levels were sustained for more than 90 min in mice. The increase was significantly delayed compared with the reported timing of plasma and tissue levels of l-ornithine after administration. The l-ornithine-induced increase in GH release was completely blocked by [D-Lys3]-GHRP-6, a ghrelin receptor antagonist, but not by cyclosomatostatin or JV-1-38, antagonists of somatostatin and GH-releasing hormone, respectively. These results suggest the involvement of ghrelin receptor-mediated pathways in l-ornithine-induced increases in GH release.
    Keywords:  ghrelin; growth hormone; growth hormone-releasing hormone; ornithine; somatostatin
    DOI:  https://doi.org/10.1292/jvms.22-0125
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