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Search Results: 1 - 10 of 2405 matches for " Silvana Hrelia "
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Quercetin Reduces Inflammatory Responses in LPS-Stimulated Cardiomyoblasts
Cristina Angeloni,Silvana Hrelia
Oxidative Medicine and Cellular Longevity , 2012, DOI: 10.1155/2012/837104
Abstract: Flavonoids possess several biological and pharmacological activities. Quercetin (Q), a naturally occurring flavonoid, has been shown to downregulate inflammatory responses and provide cardioprotection. However, the mechanisms behind the anti-inflammatory properties of Q in cardiac cells are poorly understood. In inflammation, nitric oxide (NO) acts as a proinflammatory mediator and is synthesized by inducible nitric oxide synthase (iNOS) in response to pro-inflammatory agents such as lipopolysaccharide (LPS), a causative agent in myocardial depression during sepsis. In the present study, we evaluated the protective effect of Q on rat cardiac dysfunction during sepsis induced by LPS. Pretreatment of H9c2 cardiomyoblasts with Q inhibited LPS-induced iNOS expression and NO production and counteracted oxidative stress caused by the unregulated NO production that leads to the generation of peroxynitrite and other reactive nitrogen species. In addition, Q pretreatment significantly counteracted apoptosis cell death as measured by immunoblotting of the cleaved caspase 3 and caspase 3 activity. Q also inhibited the LPS-induced phosphorylation of the stress-activated protein kinases (JNK/SAPK) and p38 MAP kinase that are involved in the inhibition of cell growth as well as the induction of apoptosis. In conclusion, these results suggest that Q might serve as a valuable protective agent in cardiovascular inflammatory diseases.
Dietary Phenolic Acids Act as Effective Antioxidants in Membrane Models and in Cultured Cells, Exhibiting Proapoptotic Effects in Leukaemia Cells
Laura Zambonin,Cristiana Caliceti,Francesco Vieceli Dalla Sega,Diana Fiorentini,Silvana Hrelia,Laura Landi,Cecilia Prata
Oxidative Medicine and Cellular Longevity , 2012, DOI: 10.1155/2012/839298
Abstract: Caffeic, syringic, and protocatechuic acids are phenolic acids derived directly from food intake or come from the gut metabolism of polyphenols. In this study, the antioxidant activity of these compounds was at first evaluated in membrane models, where caffeic acid behaved as a very effective chain-breaking antioxidant, whereas syringic and protocatechuic acids were only retardants of lipid peroxidation. However, all three compounds acted as good scavengers of reactive species in cultured cells subjected to exogenous oxidative stress produced by low level of H2O2. Many tumour cells are characterised by increased ROS levels compared with their noncancerous counterparts. Therefore, we investigated whether phenolic acids, at low concentrations, comparable to those present in human plasma, were able to decrease basal reactive species. Results show that phenolic acids reduced ROS in a leukaemia cell line (HEL), whereas no effect was observed in normal cells, such as HUVEC. The compounds exhibited no toxicity to normal cells while they decreased proliferation in leukaemia cells, inducing apoptosis. In the debate on optimal ROS-manipulating strategies in cancer therapy, our work in leukaemia cells supports the antioxidant ROS-depleting approach.
Effect of Plasma Membrane Cholesterol Depletion on Glucose Transport Regulation in Leukemia Cells
Cristiana Caliceti, Laura Zambonin, Cecilia Prata, Francesco Vieceli Dalla Sega, Gabriele Hakim, Silvana Hrelia, Diana Fiorentini
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0041246
Abstract: GLUT1 is the predominant glucose transporter in leukemia cells, and the modulation of glucose transport activity by cytokines, oncogenes or metabolic stresses is essential for their survival and proliferation. However, the molecular mechanisms allowing to control GLUT1 trafficking and degradation are still under debate. In this study we investigated whether plasma membrane cholesterol depletion plays a role in glucose transport activity in M07e cells, a human megakaryocytic leukemia line. To this purpose, the effect of cholesterol depletion by methyl-β-cyclodextrin (MBCD) on both GLUT1 activity and trafficking was compared to that of the cytokine Stem Cell Factor (SCF). Results show that, like SCF, MBCD led to an increased glucose transport rate and caused a subcellular redistribution of GLUT1, recruiting intracellular transporter molecules to the plasma membrane. Due to the role of caveolae/lipid rafts in GLUT1 stimulation in response to many stimuli, we have also investigated the GLUT1 distribution along the fractions obtained after non ionic detergent treatment and density gradient centrifugation, which was only slightly changed upon MBCD treatment. The data suggest that MBCD exerts its action via a cholesterol-dependent mechanism that ultimately results in augmented GLUT1 translocation. Moreover, cholesterol depletion triggers GLUT1 translocation without the involvement of c-kit signalling pathway, in fact MBCD effect does not involve Akt and PLCγ phosphorylation. These data, together with the observation that the combined MBCD/SCF cell treatment caused an additive effect on glucose uptake, suggest that the action of SCF and MBCD may proceed through two distinct mechanisms, the former following a signalling pathway, and the latter possibly involving a novel cholesterol dependent mechanism.
Phytochemical Profile and Nutraceutical Value of Old and Modern Common Wheat Cultivars
Emanuela Leoncini, Cecilia Prata, Marco Malaguti, Ilaria Marotti, Antonio Segura-Carretero, Pietro Catizone, Giovanni Dinelli, Silvana Hrelia
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0045997
Abstract: Among health-promoting phytochemicals in whole grains, phenolic compounds have gained attention as they have strong antioxidant properties and can protect against many degenerative diseases. Aim of this study was to profile grain phenolic extracts of one modern and five old common wheat (Triticum aestivum L.) varieties and to evaluate their potential antiproliferative or cytoprotective effect in different cell culture systems. Wheat extracts were characterized in terms of antioxidant activity and phenolic composition (HPLC/ESI-TOF-MS profile, polyphenol and flavonoid contents). Results showed that antioxidant activity (FRAP and DPPH) is mostly influenced by flavonoid (both bound and free) content and by the ratio flavonoids/polyphenols. Using a leukemic cell line, HL60, and primary cultures of neonatal rat cardiomyocytes, the potential antiproliferative or cytoprotective effects of different wheat genotypes were evaluated in terms of intracellular reactive oxygen species levels and cell viability. All tested wheat phenolic extracts exerted dose-dependent cytoprotective and antiproliferative effects on cardiomyocytes and HL60 cells, respectively. Due to the peculiar phenolic pattern of each wheat variety, a significant genotype effect was highlighted. On the whole, the most relevant scavenging effect was found for the old variety Verna. No significant differences in terms of anti-proliferative activities among wheat genotypes was observed. Results reported in this study evidenced a correspondence between the in vitro antioxidant activity and potential healthy properties of different extracts. This suggests that an increased intake of wheat grain derived products could represent an effective strategy to achieve both chemoprevention and protection against oxidative stress related diseases.
Steviol Glycosides Modulate Glucose Transport in Different Cell Types
Benedetta Rizzo,Laura Zambonin,Cristina Angeloni,Emanuela Leoncini,Francesco Vieceli Dalla Sega,Cecilia Prata,Diana Fiorentini,Silvana Hrelia
Oxidative Medicine and Cellular Longevity , 2013, DOI: 10.1155/2013/348169
Abstract: Extracts from Stevia rebaudiana Bertoni, a plant native to Central and South America, have been used as a sweetener since ancient times. Currently, Stevia extracts are largely used as a noncaloric high-potency biosweetener alternative to sugar, due to the growing incidence of type 2 diabetes mellitus, obesity, and metabolic disorders worldwide. Despite the large number of studies on Stevia and steviol glycosides in vivo, little is reported concerning the cellular and molecular mechanisms underpinning the beneficial effects on human health. The effect of four commercial Stevia extracts on glucose transport activity was evaluated in HL-60 human leukaemia and in SH-SY5Y human neuroblastoma cells. The extracts were able to enhance glucose uptake in both cellular lines, as efficiently as insulin. Our data suggest that steviol glycosides could act by modulating GLUT translocation through the PI3K/Akt pathway since treatments with both insulin and Stevia extracts increased the phosphorylation of PI3K and Akt. Furthermore, Stevia extracts were able to revert the effect of the reduction of glucose uptake caused by methylglyoxal, an inhibitor of the insulin receptor/PI3K/Akt pathway. These results corroborate the hypothesis that Stevia extracts could mimic insulin effects modulating PI3K/Akt pathway. 1. Introduction Stevia rebaudiana Bertoni is a weak perennial shrub belonging to Asteraceae (Compositae) family, native to subtropical regions of Brazil and Paraguay. Its leaves have been used as a sweetener since ancient times and for many other medicinal purposes in Latin America and the Orient for centuries [1, 2]. The “sweet herb” has gained increasing interest from nutritional researchers and commercial area in the last years, due to the growing need to find new natural calorie-free sweeteners alternative to sugar. Indeed, in both industrialized and developing countries, the incidence of type 2 diabetes mellitus and obesity is sharply increasing as a result of dietary behaviours, reduced physical activities, and ageing. These metabolic disorders have become major public health problems worldwide [3, 4]. Glycemic control is fundamental to the management of diabetes since it is associated with significantly decreased rates of retinopathy, nephropathy, neuropathy, and cardiovascular disease, the most common cause of death in diabetic patients. The effort to achieve near-normoglycemia through the key strategy of glycemic control includes recommendations for prevention and control of diabetes, for example, monitoring carbohydrate intake and limiting the consumption
Long-Term IGF-I Exposure Decreases Autophagy and Cell Viability
Alessandro Bitto,Chad Lerner,Claudio Torres,Michaela Roell,Marco Malaguti,Viviana Perez,Antonello Lorenzini,Silvana Hrelia,Yuji Ikeno,Michelle Elizabeth Matzko,Roger McCarter,Christian Sell
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0012592
Abstract: A reduction in IGF-I signaling has been found to increase lifespan in multiple organisms despite the fact that IGF-I is a trophic factor for many cell types and has been found to have protective effects against multiple forms of damage in acute settings. The increase in longevity seen in response to reduced IGF-I signaling suggests that there may be differences between the acute and chronic impact of IGF-I signaling. We have examined the possibility that long-term stimulation with IGF-I may have a negative impact at the cellular level using quiescent human fibroblasts. We find that fibroblast cells exposed to IGF-I for 14 days have reduced long-term viability as judged by colony forming assays, which is accompanied by an accumulation of senescent cells. In addition we observe an accumulation of cells with depolarized mitochondria and a reduction in autophagy in the long-term IGF-I treated cultures. An examination of mice with reduced IGF-I levels reveals evidence of enhanced autophagy and fibroblast cells derived from these mice have a larger mitochondrial mass relative to controls indicating that changes in mitochondrial turnover occurs in animals with reduced IGF-I. The results indicate that chronic IGF-I stimulation leads to mitochondrial dysfunction and reduced cell viability.
Novel Targets of Sulforaphane in Primary Cardiomyocytes Identified by Proteomic Analysis
Cristina Angeloni, Silvia Turroni, Laura Bianchi, Daniele Fabbri, Elisa Motori, Marco Malaguti, Emanuela Leoncini, Tullia Maraldi, Luca Bini, Patrizia Brigidi, Silvana Hrelia
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0083283
Abstract: Cardiovascular diseases represent the main cause of mortality in the industrialized world and the identification of effective preventive strategies is of fundamental importance. Sulforaphane, an isothiocyanate from cruciferous vegetables, has been shown to up-regulate phase II enzymes in cardiomyocytes and counteract oxidative stress-induced apoptosis. Aim of the present study was the identification and characterization of novel sulforaphane targets in cardiomyocytes applying a proteomic approach. Two-dimensional gel electrophoresis and mass spectrometry were used to generate protein profiles of primary neonatal rat cardiomyocytes treated and untreated with 5 μM sulforaphane for 1-48 h. According to image analysis, 64 protein spots were found as differentially expressed and their functional correlations were investigated using the MetaCore program. We mainly focused on 3 proteins: macrophage migration inhibitory factor (MIF), CLP36 or Elfin, and glyoxalase 1, due to their possible involvement in cardioprotection. Validation of the time-dependent differential expression of these proteins was performed by western blotting. In particular, to gain insight into the cardioprotective role of the modulation of glyoxalase 1 by sulforaphane, further experiments were performed using methylglyoxal to mimic glycative stress. Sulforaphane was able to counteract methylglyoxal-induced apoptosis, ROS production, and glycative stress, likely through glyoxalase 1 up-regulation. In this study, we reported for the first time new molecular targets of sulforaphane, such as MIF, CLP36 and glyoxalase 1. In particular, we gave new insights into the anti-glycative role of sulforaphane in cardiomyocytes, confirming its pleiotropic behavior in counteracting cardiovascular diseases.
17β-Estradiol Enhances Signalling Mediated by VEGF-A-Delta-Like Ligand 4-Notch1 Axis in Human Endothelial Cells
Cristiana Caliceti, Giorgio Aquila, Micaela Pannella, Marco Bruno Morelli, Cinzia Fortini, Paolo Pinton, Massimo Bonora, Silvana Hrelia, Antonio Pannuti, Lucio Miele, Paola Rizzo, Roberto Ferrari
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0071440
Abstract: Estrogens play a protective role in coronary artery disease. The mechanisms of action are still poorly understood, although a role for estrogens in stimulation of angiogenesis has been suggested. In several cell types, estrogens modulate the Notch pathway, which is involved in controlling angiogenesis downstream of vascular endothelial growth factor A (VEGF-A). The goal of our study was to establish whether estrogens modulate Notch activity in endothelial cells and the possible consequences on angiogenesis. Human umbilical vein endothelial cells (HUVECs) were treated with 17β-estradiol (E2) and the effects on Notch signalling were evaluated. E2 increased Notch1 processing as indicated by i) decreased levels of Notch1 transmembrane subunit ii) increased amount of Notch1 in nuclei iii) unaffected level of mRNA. Similarly, E2 increased the levels of the active form of Notch4 without altering Notch4 mRNA. Conversely, protein and mRNA levels of Notch2 were both reduced suggesting transcriptional repression of Notch2 by E2. Under conditions where Notch was activated by upregulation of Delta-like ligand 4 (Dll4) following VEGF-A treatment, E2 caused a further increase of the active form of Notch1, of the number of cells with nuclear Notch1 and of Hey2 mRNA. Estrogen receptor antagonist ICI 182.780 antagonized these effects suggesting that E2 modulation of Notch1 is mediated by estrogen receptors. E2 treatment abolished the increase in endothelial cells sprouting caused by Notch inhibition in a tube formation assay on 3D Matrigel and in mouse aortic ring explants. In conclusion, E2 affects several Notch pathway components in HUVECs, leading to an activation of the VEGF-A-Dll4-Notch1 axis and to a modulation of vascular branching when Notch signalling is inhibited. These results contribute to our understanding of the molecular mechanisms of cardiovascular protection exerted by estrogens by uncovering a novel role of E2 in the Notch signalling-mediated modulation of angiogenesis.
Simplifying Stochastic Mathematical Models of Biochemical Systems  [PDF]
Silvana Ilie, Samaneh Gholami
Applied Mathematics (AM) , 2013, DOI: 10.4236/am.2013.41A038

Stochastic modeling of biochemical reactions taking place at the cellular level has become the subject of intense research in recent years. Molecular interactions in a single cell exhibit random fluctuations. These fluctuations may be significant when small populations of some reacting species are present and then a stochastic description of the cellular dynamics is required. Often, the biochemically reacting systems encountered in applications consist of many species interacting through many reaction channels. Also, the dynamics of such systems is typically non-linear and presents multiple time-scales. Consequently, the stochastic mathematical models of biochemical systems can be quite complex and their analysis challenging. In this paper, we present a method to reduce a stochastic continuous model of well-stirred biochemical systems, the Chemical Langevin Equation, while preserving the overall behavior of the system. Several tests of our method on models of practical interest gave excellent results.

Automatic Simulation of the Chemical Langevin Equation  [PDF]
Silvana Ilie, Monjur Morshed
Applied Mathematics (AM) , 2013, DOI: 10.4236/am.2013.41A036

Biochemical systems have important practical applications, in particular to understanding critical intra-cellular processes. Often biochemical kinetic models represent cellular processes as systems of chemical reactions, traditionally modeled by the deterministic reaction rate equations. In the cellular environment, many biological processes are inherently stochastic. The stochastic fluctuations due to the presence of some low molecular populations may have a great impact on the biochemical system behavior. Then, stochastic models are required for an accurate description of the system dynamics. An important stochastic model of biochemical kinetics is the Chemical Langevin Equation. In this work, we provide a numerical method for approximating the solution of the Chemical Langevin Equation, namely the derivative-free Milstein scheme. The method is compared with the widely used strategy for this class of problems, the Milstein method. As opposed to the Milstein scheme, the proposed strategy has the advantage that it does not require the calculation of exact derivatives, while having the same strong order of accuracy as the Milstein scheme. Therefore it may be used for an automatic simulation of the numerical solution of the Chemical Langevin Equation. The tests on several models of practical interest show that our method performs very well.

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