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Cellular Physiology and Biochemistry :... 2016Endoplasmic reticulum stress (ERS) plays an important role in the progression of acute myocardial infarction (AMI), in part by mediating apoptosis. Polyamines, including...
BACKGROUND/AIMS
Endoplasmic reticulum stress (ERS) plays an important role in the progression of acute myocardial infarction (AMI), in part by mediating apoptosis. Polyamines, including putrescine, spermidine, and spermine, are polycations with anti-oxidative, anti-aging, and cell growth-promoting activities. This study aimed to determine the mechanisms by which spermine protects against ERS-induced apoptosis in rats following AMI.
METHODS AND RESULTS
AMI was established by ligation of the left anterior descending coronary artery (LAD) in rats, and exogenous spermine was administered by intraperitoneal injection (2.5 mg/ml daily for 7 days pre-AMI). Spermine treatment limited infarct size, attenuated cardiac troponin I and creatinine kinase-MB release, improved cardiac function, and decreased ERS and apoptosis related protein expression. Isolated cardiomyocytes subjected to hypoxia showed significant increase in reactive oxygen species (ROS) and the expression of apoptosis and ERS related proteins; these effects occurred through PERK and eIF2α phosphorylation. The addition of spermine attenuated cardiomyocyte apoptosis, suppressed the production of ROS, and inhibited ERS related pathways.
CONCLUSIONS
Spermine was an effective pre-treatment strategy to attenuate cardiac ERS injury in rats, and the cardioprotective mechanism occurring through inhibition of ROS production and down regulation of the PERK-eIF2α pathway. These findings provide a novel target for the prevention of apoptosis in the setting of AMI.
Topics: Animals; Apoptosis; Cells, Cultured; Endoplasmic Reticulum Stress; Male; Myocardial Infarction; Myocardium; Myocytes, Cardiac; Rats; Rats, Wistar; Reactive Oxygen Species; Spermine; Troponin I
PubMed: 26828926
DOI: 10.1159/000438648 -
Kidney International Jan 1987The polyamine spermine has been reported to be the inhibitor of in vitro erythropoiesis present in uremic serum. We have employed a panel of hematopoietic colony-forming...
The polyamine spermine has been reported to be the inhibitor of in vitro erythropoiesis present in uremic serum. We have employed a panel of hematopoietic colony-forming assays to evaluate the specificity of the inhibitory activity. Spermine and its precursor spermidine when added to culture inhibited mouse and human erythroid (CFU-E and BFU-E), granulocyte-macrophage, and megakaryocyte colony growth in a non-specific, dose-dependent fashion. Erythroid and non-erythroid colony growth were equally sensitive to spermine- and spermidine-induced inhibition. Increasing concentrations in culture of erythropoietin and mitogen-stimulated leukocyte-conditioned medium, a source of colony-stimulating activity, failed to overcome the in vitro inhibition. Although anemia is characteristic of chronic renal failure (CRF), leukopenia and thrombocytopenia are not. Therefore, we conclude that the non-specific inhibitory activity of spermine and spermidine, as defined by in vitro colony assays, is either of no pathophysiologic significance in the anemia of CRF, or else there are unrecognized repair mechanisms in vivo which maintain granulopoiesis and thrombopoiesis at normal levels.
Topics: Animals; Bone Marrow; Cells, Cultured; Colony-Forming Units Assay; Hematopoiesis; Hematopoietic Stem Cells; Humans; Male; Mice; Mice, Inbred C57BL; Spermidine; Spermine
PubMed: 3560647
DOI: 10.1038/ki.1987.11 -
Organic & Biomolecular Chemistry Jul 2019The bifunctional ligand p-SCN-Bn-HOPO, which has four 1,2-hydroxypyridinone groups on a spermine backbone with an isothiocyanate linker, has been shown to be an...
The bifunctional ligand p-SCN-Bn-HOPO, which has four 1,2-hydroxypyridinone groups on a spermine backbone with an isothiocyanate linker, has been shown to be an efficient and stable chelator for Zr(iv) and, more importantly, the radioisotope 89Zr for use in radiolabeling antibodies for positron emission tomography (PET) imaging. Previous studies of 89Zr-HOPO-trastuzumab in mice showed low background, good tumor to organ contrast, and very low bone uptake which show p-SCN-Bn-HOPO to be an important next-generation bifunctional chelator for radioimmunoPET imaging with 89Zr. However, the reported synthesis of p-SCN-Bn-HOPO involves nine steps and multiple HPLC purifications with an overall yield of about 1.4%. Herein we report an improved and efficient synthesis of p-SCN-Bn-HOPO in four steps with 14.3% overall yield which will improve its availability for further biological studies and wider application in PET imaging. The new synthetic route also allows variation in linker length and chemistries which may be helpful in modifying in vivo clearance behaviors of future agents.
Topics: Chelating Agents; Molecular Structure; Positron-Emission Tomography; Pyridones; Spermine
PubMed: 31268109
DOI: 10.1039/c9ob01068h -
Chemico-biological Interactions Jun 2024Chronic inflammation, oxidative stress, and airway remodelling represent the principal pathophysiological features of chronic respiratory disorders. Inflammation stimuli...
Chronic inflammation, oxidative stress, and airway remodelling represent the principal pathophysiological features of chronic respiratory disorders. Inflammation stimuli like lipopolysaccharide (LPS) activate macrophages and dendritic cells, with concomitant M1 polarization and release of pro-inflammatory cytokines. Chronic inflammation and oxidative stress lead to airway remodelling causing irreversible functional and structural alterations of the lungs. Airway remodelling is multifactorial, however, the hormone transforming growth factor-β (TGF-β) is one of the main contributors to fibrotic changes. The signalling pathways mediating inflammation and remodelling rely both on the transcription factor nuclear factor-κB (NFκB), underlying the potential of NFκB inhibition as a therapeutic strategy for chronic respiratory disorders. In this study, we encapsulated an NFκB-inhibiting decoy oligodeoxynucleotide (ODN) in spermine-functionalized acetalated dextran (SpAcDex) nanoparticles and tested the in vitro anti-inflammatory and anti-remodelling activity of this formulation. We show that NF-κB ODN nanoparticles counteract inflammation by reversing LPS-induced expression of the activation marker CD40 in myeloid cells and counteracts remodelling features by reversing the TGF-β-induced expression of collagen I and α-smooth muscle actin in human dermal fibroblast. In summary, our study highlights the great potential of inhibiting NFκB via decoy ODN as a therapeutic strategy tackling multiple pathophysiological features underlying chronic respiratory conditions.
Topics: Oligodeoxyribonucleotides; Humans; Nanoparticles; Anti-Inflammatory Agents; NF-kappa B; Spermine; Lipopolysaccharides; Transforming Growth Factor beta; Fibroblasts; Fibrosis
PubMed: 38761875
DOI: 10.1016/j.cbi.2024.111059 -
Biochemistry. Biokhimiia Oct 2012Influence of the biogenic polyamines spermine, spermidine, and putrescine as well as their derivatives on the replication enzymes of hepatitis C virus (HCV) was...
Influence of the biogenic polyamines spermine, spermidine, and putrescine as well as their derivatives on the replication enzymes of hepatitis C virus (HCV) was investigated. It was found that spermine and spermidine activate HCV RNA-dependent RNA polymerase (NS5B protein). This effect was not caused by the stabilization of the enzyme or by competition with template-primer complex, but rather it was due to achievement of true maximum velocity V(max). Natural polyamines and their derivatives effectively inhibited the helicase reaction catalyzed by another enzyme of HCV replication - helicase/NTPase (NS3 protein). However, these compounds affected neither the NTPase reaction nor its activation by polynucleotides. Activation of the HCV RNA polymerase and inhibition of the viral helicase were shown at physiological concentrations of the polyamines. These data suggest that biogenic polyamines may cause differently directed effects on the replication of the HCV genome in an infected cell.
Topics: Enzyme Activation; Hepacivirus; Humans; Putrescine; RNA Helicases; RNA-Dependent RNA Polymerase; Spermidine; Spermine; Viral Nonstructural Proteins
PubMed: 23157297
DOI: 10.1134/S0006297912100094 -
Sensors (Basel, Switzerland) Dec 2022The evaluation of the biogenic amines (BAs) profile of different types of craft beers is herein presented. A previously developed and validated analytical method based...
The evaluation of the biogenic amines (BAs) profile of different types of craft beers is herein presented. A previously developed and validated analytical method based on ion-pair chromatography coupled with potentiometric detection was used to determine the presence of 10 BAs. Good analytical features were obtained for all amines regarding linearity (R values from 0.9873 ± 0.0015 to 0.9973 ± 0.0015), intra- and inter-day precision (RSD lower than 6.9% and 9.7% for beer samples, respectively), and accuracy (recovery between 83.2-108.9%). Detection and quantification limits range from 9.3 to 60.5 and from 31.1 to 202.3 µg L, respectively. The validated method was applied to the analysis of four ale beers and one lager craft beer. Ethylamine, spermidine, spermine, and tyramine were detected in all analyzed samples while methylamine and phenylethylamine were not detected. Overall, pale ale beers had a significantly higher total content of BAs than those found in wheat pale and dark samples. A general least square regression model showed a good correlation between the total content of BAs and the brewing process, especially for Plato degree, mashing, and fermentation temperatures. Knowledge about the type of ingredients and manufacturing processes that contribute to higher concentrations of these compounds is crucial to ensuring consumer safety.
Topics: Beer; Biogenic Amines; Chromatography, High Pressure Liquid; Spermidine; Spermine
PubMed: 36616940
DOI: 10.3390/s23010343 -
Neurobiology of Disease Jul 2021Subanesthetic doses of ketamine induce schizophrenia-like behaviors in mice including hyperlocomotion and deficits in working memory and sensorimotor gating. Here, we...
Subanesthetic doses of ketamine induce schizophrenia-like behaviors in mice including hyperlocomotion and deficits in working memory and sensorimotor gating. Here, we examined the effect of in vivo ketamine administration on neuronal properties and endocannabinoid (eCB)-dependent modulation of synaptic transmission onto layer 2/3 pyramidal neurons in brain slices of the prefrontal cortex, a region tied to the schizophrenia-like behavioral phenotypes of ketamine. Since deficits in working memory and sensorimotor gating are tied to activation of the tyrosine phosphatase PTP1B in glutamatergic neurons, we asked whether PTP1B contributes to these effects of ketamine. Ketamine increased membrane resistance and excitability of pyramidal neurons. Systemic pharmacological inhibition of PTP1B by Trodusquemine restored these neuronal properties and prevented each of the three main ketamine-induced behavior deficits. Ketamine also reduced mobilization of eCB by pyramidal neurons, while unexpectedly reducing their inhibitory inputs, and these effects of ketamine were blocked or occluded by PTP1B ablation in glutamatergic neurons. While ablation of PTP1B in glutamatergic neurons prevented ketamine-induced deficits in memory and sensorimotor gating, it failed to prevent hyperlocomotion (a psychosis-like phenotype). Taken together, these results suggest that PTP1B in glutamatergic neurons mediates ketamine-induced deficits in eCB mobilization, memory and sensorimotor gating whereas PTP1B in other cell types contributes to hyperlocomotion. Our study suggests that the PTP1B inhibitor Trodusquemine may represent a new class of fast-acting antipsychotic drugs to treat schizophrenia-like symptoms.
Topics: Adaptor Proteins, Signal Transducing; Anesthetics, Dissociative; Animals; Cholestanes; Dose-Response Relationship, Drug; Ketamine; LIM Domain Proteins; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, Transgenic; Protein Tyrosine Phosphatase, Non-Receptor Type 1; Schizophrenia; Spermine
PubMed: 34015491
DOI: 10.1016/j.nbd.2021.105397 -
PloS One 2016The present work is aimed at evaluating the antitumour properties of a Pd(II) dinuclear complex with the biogenic polyamine spermine, by investigating: i) the...
The present work is aimed at evaluating the antitumour properties of a Pd(II) dinuclear complex with the biogenic polyamine spermine, by investigating: i) the anti-angiogenic and anti-migration properties of a Pd(II) dinuclear complex with spermine (Pd2Spm); ii) the anti-proliferative activity of Pd2Spm against a triple negative human breast carcinoma (MDA-MB-231); and finally iii) the putative interaction mediated by combination of Pd2Spm with Docetaxel. Anti-invasive (anti-angiogenic and anti-migratory) as well as anti-proliferative capacities were assessed, for different combination schemes and drug exposure times, using the CAM assay and VEGFR2 activity measurement, the MatrigelTM method and the SRB proliferation test. The results thus obtained evidence the ability of Pd2Spm to restrict angiogenesis and cell migration: Pd2Spm induced a marked inhibition of migration (43.8±12.2%), and a higher inhibition of angiogenesis (81.8±4.4% for total length values, at 4 μM) as compared to DTX at the clinical dosage 4x10-2 μM (26.4±14.4%; n = 4 to 11). Combination of Pd2Spm/DTX was more effective as anti-invasive and anti-proliferative than DTX or Pd2Spm in sole administration, which is compatible with the occurrence of synergism: for the anti-angiogenic effect, IC50(Pd2Spm/DTX) = 0.5/0.5x10-2 μM vs IC50(DTX) = 1.7x10-2 μM and IC50(Pd2Spm) = 1.6 μM. In conclusion, the reported effects of Pd2Spm on angiogenesis, migration and proliferation showed that this compound is a promising therapeutic agent against this type of breast cancer. Moreover, combined administration of Pd2Spm and DTX was found to trigger a substantial synergetic effect regarding angiogenesis inhibition as well as anti-migratory and anti-proliferative activities reinforcing the putative use of Pd(II) complexes in chemotherapeutic regimens. This is a significant outcome, aiming at the application of these combined strategies towards metastatic breast cancer (or other type of resistant cancers), justifying further studies that include pre-clinical trials.
Topics: Animals; Avian Proteins; Breast Neoplasms; Cell Movement; Cell Proliferation; Chick Embryo; Chickens; Docetaxel; Drug Screening Assays, Antitumor; Drug Synergism; Female; Humans; Neovascularization, Pathologic; Palladium; Spermine; Taxoids; Vascular Endothelial Growth Factor Receptor-2
PubMed: 27880824
DOI: 10.1371/journal.pone.0167218 -
Journal of Bacteriology Dec 1966Groman, Neal B. (University of Washington, Seattle), and Grace Suzuki. Effect of spermine on lysis and reproduction by bacteriophages phiX174, lambda, and f(2). J....
Groman, Neal B. (University of Washington, Seattle), and Grace Suzuki. Effect of spermine on lysis and reproduction by bacteriophages phiX174, lambda, and f(2). J. Bacteriol. 92:1735-1740. 1966.-A test was made of the hypothesis that lysis by all bacteriophages shares as a common and critical step an alteration in the osmotic stability of the infected cell. This was done by examining the effect of spermine on lysis. Spermine is one of a number of compounds which can stabilize spheroplasts and protoplasts to lysis in distilled water. Spermine stabilized both phiX174- and f(2)-infected cells at concentrations ranging from 2 x 10(-3) to 4 x 10(-2)m, but failed to stabilize lambda-infected cells at concentrations up to 8 x 10(-2)m. Stabilization was reflected both in optical density measurements and in the retention of mature phage in structures sedimentable at low speeds. At optimal concentration, over 90% of the phage was retained in these structures. These data suggest that the mechanism of lysis by phiX174 and f(2) differs sharply from that caused by lambda, and other observations suggest that there are differences in the lytic process of phiX174 and f(2) as well. Spermine also displayed a differential effect on phage reproduction. The reproduction of lambda and f(2) was inhibited by spermine, though the data do indicate that maturation occurs in its presence. The reproduction of phiX174 was enhanced by spermine.
Topics: Bacteriolysis; Coliphages; Spermine
PubMed: 5958108
DOI: 10.1128/jb.92.6.1735-1740.1966 -
Food Chemistry Jul 2015The influence of somatic cells counts (SCC) in milk on bioactive amines in Mozzarella cheese was investigated. High SCC milk had lower lactose and higher pH compared to...
The influence of somatic cells counts (SCC) in milk on bioactive amines in Mozzarella cheese was investigated. High SCC milk had lower lactose and higher pH compared to low and medium SCC. Low spermine levels were found in milk irrespective of SCC. The cheeses had similar characteristics, but the extension and depth of proteolysis increased with SCC. Cheese from all SCC categories contained spermine; whereas tyramine and tryptamine were only detected in cheese from high SCC milk. During 60-days refrigerated storage, significant positive effects were observed between SCC and proteolysis, storage time and pH and storage time and proteolysis. There was a significant positive effect of storage time on spermine and serotonin levels. Only cheese from high SCC milk showed significantly higher serotonin levels. Tyramine and tryptamine were found in cheese from high SCC milk.
Topics: Animals; Biogenic Amines; Cattle; Cell Count; Cheese; Food Storage; Milk; Serotonin; Spermine
PubMed: 25704706
DOI: 10.1016/j.foodchem.2015.01.084