Publications by authors named "Giuseppina Raciti"

30 Publications

  • Page 1 of 1

Role of Cigarette Smoke on Angiotensin-Converting Enzyme-2 Protein Membrane Expression in Bronchial Epithelial Cells Using an Air-Liquid Interface Model.

Front Pharmacol 2021 30;12:652102. Epub 2021 Mar 30.

Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy.

Prevalence studies of current smoking, among hospitalized COVID-19 patients, demonstrated an unexpectedly low prevalence among patients with COVID-19. The aim of the present study was to evaluate the effect of smoke from cigarettes on ACE-2 in bronchial epithelial cells. Normal bronchial epithelial cells (H292) were exposed to smoke by an air-liquid-interface (ALI) system and ACE-2 membrane protein expression was evaluated after 24 h from exposure. Our transcriptomics data analysis showed a significant selective reduction of membrane ACE-2 expression (about 25%) following smoking exposure. Interestingly, we observed a positive direct correlation between ACE-2 reduction and nicotine delivery. Furthermore, by stratifying GSE52237 as a function of ACE-2 gene expression levels, we highlighted 1,012 genes related to ACE-2 in smokers and 855 in non-smokers. Furthermore, we showed that 161 genes involved in the endocytosis process were highlighted using the online pathway tool KEGG. Finally, 11 genes were in common between the ACE-2 pathway in smokers and the genes regulated during endocytosis, while 12 genes with non-smokers. Interestingly, six in non-smokers and four genes in smokers were closely involved during the viral internalization process. Our data may offer a pharmaceutical role of nicotine as potential treatment option in COVID-19.
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http://dx.doi.org/10.3389/fphar.2021.652102DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8042260PMC
March 2021

Amyloid-Beta Induces Different Expression Pattern of Tissue Transglutaminase and Its Isoforms on Olfactory Ensheathing Cells: Modulatory Effect of Indicaxanthin.

Int J Mol Sci 2021 Mar 25;22(7). Epub 2021 Mar 25.

Institute for Biomedical Research and Innovation (IRIB), National Research Council, 95126 Catania, Italy.

Herein, we assessed the effect of full native peptide of amyloid-beta (Aβ) (1-42) and its fragments (25-35 and 35-25) on tissue transglutaminase (TG2) and its isoforms (TG2-Long and TG2-Short) expression levels on olfactory ensheathing cells (OECs). Vimentin and glial fibrillary acid protein (GFAP) were also studied. The effect of the pre-treatment with indicaxanthin from Opuntia ficus-indica fruit on TG2 expression levels and its isoforms, cell viability, total reactive oxygen species (ROS), superoxide anion (O), and apoptotic pathway activation was assessed. The levels of Nestin and cyclin D1 were also evaluated. Our findings highlight that OECs exposure to Aβ(1-42) and its fragments induced an increase in TG2 expression levels and a different expression pattern of its isoforms. Indicaxanthin pre-treatment reduced TG2 overexpression, modulating the expression of TG2 isoforms. It reduced total ROS and O production, GFAP and Vimentin levels, inhibiting apoptotic pathway activation. It also induced an increase in the Nestin and cyclin D1 expression levels. Our data demonstrated that indicaxanthin pre-treatment stimulated OECs self-renewal through the reparative activity played by TG2. They also suggest that Aβ might modify TG2 conformation in OECs and that indicaxanthin pre-treatment might modulate TG2 conformation, stimulating neural regeneration in Alzheimer's disease.
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http://dx.doi.org/10.3390/ijms22073388DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8037686PMC
March 2021

Current molecular and clinical insights into uveal melanoma (Review).

Int J Oncol 2021 04 2;58(4). Epub 2021 Mar 2.

Department of Ophthalmology, University of Catania, I‑95123 Catania, Italy.

Uveal melanoma (UM) represents the most prominent primary eye cancer in adults. With an incidence of approximately 5 cases per million individuals annually in the United States, UM could be considered a relatively rare cancer. The 90‑95% of UM cases arise from the choroid. Diagnosis is based mainly on a clinical examination and ancillary tests, with ocular ultrasonography being of greatest value. Differential diagnosis can prove challenging in the case of indeterminate choroidal lesions and, sometimes, monitoring for documented growth may be the proper approach. Fine needle aspiration biopsy tends to be performed with a prognostic purpose, often in combination with radiotherapy. Gene expression profiling has allowed for the grading of UMs into two classes, which feature different metastatic risks. Patients with UM require a specialized multidisciplinary management. Primary tumor treatment can be either enucleation or globe preserving. Usually, enucleation is reserved for larger tumors, while radiotherapy is preferred for small/medium melanomas. The prognosis is unfavorable due to the high mortality rate and high tendency to metastasize. Following the development of metastatic disease, the mortality rate increases to 80% within one year, due to both the absence of an effective treatment and the aggressiveness of the condition. Novel molecular studies have allowed for a better understanding of the genetic and epigenetic mechanisms involved in UM biological activity, which differs compared to skin melanomas. The most commonly mutated genes are GNAQ, GNA11 and BAP1. Research in this field could help to identify effective diagnostic and prognostic biomarkers, as well as novel therapeutic targets.
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http://dx.doi.org/10.3892/ijo.2021.5190DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7910016PMC
April 2021

Astaxanthin-Loaded Stealth Lipid Nanoparticles (AST-SSLN) as Potential Carriers for the Treatment of Alzheimer's Disease: Formulation Development and Optimization.

Nanomaterials (Basel) 2021 Feb 3;11(2). Epub 2021 Feb 3.

Department of Drug Science and Health, University of Catania, Viale Andrea Doria 6, 95125 Catania, Italy.

Alzheimer's disease (AD) is a neurodegenerative disorder associated with marked oxidative stress at the level of the brain. Recent studies indicate that increasing the antioxidant capacity could represent a very promising therapeutic strategy for AD treatment. Astaxanthin (AST), a powerful natural antioxidant, could be a good candidate for AD treatment, although its use in clinical practice is compromised by its high instability. In order to overcome this limit, our attention focused on the development of innovative AST-loaded stealth lipid nanoparticles (AST-SSLNs) able to improve AST bioavailability in the brain. AST-SSLNs prepared by solvent-diffusion technique showed technological parameters suitable for parenteral administration (<200 nm). Formulated nanosystems were characterized by calorimetric studies, while their toxicological profile was evaluated by the MTT assay on the stem cell line OECs (Olfactory Ensheathing Cells). Furthemore, the protective effect of the nanocarriers was assessed by a long-term stability study and a UV stability assay confirming that the lipid shell of the nanocarriers was able to preserve AST concentration in the formulation. SSLNs were also capable of preserving AST's antioxidant capacity as demonstrated in the oxygen radical absorbance capacity (ORAC) assay. In conclusion, these preliminary studies outline that SSLNs could be regarded as promising carriers for systemic administration of compounds such as AST aimed at AD treatment.
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http://dx.doi.org/10.3390/nano11020391DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7913486PMC
February 2021

Immune-checkpoint inhibitors from cancer to COVID‑19: A promising avenue for the treatment of patients with COVID‑19 (Review).

Int J Oncol 2021 Feb 14;58(2):145-157. Epub 2020 Dec 14.

Section of General Pathology, Clinics and Oncology, Department of Biomedical and Biotechnological Sciences, University of Catania, I‑95123 Catania, Italy.

The severe acute respiratory syndrome associated coronavirus‑2 (SARS‑CoV‑2) poses a threat to human life worldwide. Since early March, 2020, coronavirus disease 2019 (COVID‑19), characterized by an acute and often severe form of pneumonia, has been declared a pandemic. This has led to a boom in biomedical research studies at all stages of the pipeline, from the in vitro to the clinical phase. In line with this global effort, known drugs, currently used for the treatment of other pathologies, including antivirals, immunomodulating compounds and antibodies, are currently used off‑label for the treatment of COVID‑19, in association with the supportive standard care. Yet, no effective treatments have been identified. A new hope stems from medical oncology and relies on the use of immune‑checkpoint inhibitors (ICIs). In particular, amongst the ICIs, antibodies able to block the programmed death‑1 (PD‑1)/PD ligand-1 (PD‑L1) pathway have revealed a hidden potential. In fact, patients with severe and critical COVID‑19, even prior to the appearance of acute respiratory distress syndrome, exhibit lymphocytopenia and suffer from T‑cell exhaustion, which may lead to viral sepsis and an increased mortality rate. It has been observed that cancer patients, who usually are immunocompromised, may restore their anti‑tumoral immune response when treated with ICIs. Moreover, viral-infected mice and humans, exhibit a T‑cell exhaustion, which is also observed following SARS‑CoV‑2 infection. Importantly, when treated with anti‑PD‑1 and anti‑PD‑L1 antibodies, they restore their T‑cell competence and efficiently counteract the viral infection. Based on these observations, four clinical trials are currently open, to examine the efficacy of anti‑PD‑1 antibody administration to both cancer and non‑cancer individuals affected by COVID‑19. The results may prove the hypothesis that restoring exhausted T‑cells may be a winning strategy to beat SARS‑CoV‑2 infection.
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http://dx.doi.org/10.3892/ijo.2020.5159DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7864014PMC
February 2021

In silico trial to test COVID-19 candidate vaccines: a case study with UISS platform.

BMC Bioinformatics 2020 Dec 14;21(Suppl 17):527. Epub 2020 Dec 14.

Department of Drug Sciences, University of Catania, 95125, Catania, Italy.

Background: SARS-CoV-2 is a severe respiratory infection that infects humans. Its outburst entitled it as a pandemic emergence. To get a grip on this outbreak, specific preventive and therapeutic interventions are urgently needed. It must be said that, until now, there are no existing vaccines for coronaviruses. To promptly and rapidly respond to pandemic events, the application of in silico trials can be used for designing and testing medicines against SARS-CoV-2 and speed-up the vaccine discovery pipeline, predicting any therapeutic failure and minimizing undesired effects.

Results: We present an in silico platform that showed to be in very good agreement with the latest literature in predicting SARS-CoV-2 dynamics and related immune system host response. Moreover, it has been used to predict the outcome of one of the latest suggested approach to design an effective vaccine, based on monoclonal antibody. Universal Immune System Simulator (UISS) in silico platform is potentially ready to be used as an in silico trial platform to predict the outcome of vaccination strategy against SARS-CoV-2.

Conclusions: In silico trials are showing to be powerful weapons in predicting immune responses of potential candidate vaccines. Here, UISS has been extended to be used as an in silico trial platform to speed-up and drive the discovery pipeline of vaccine against SARS-CoV-2.
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http://dx.doi.org/10.1186/s12859-020-03872-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7733700PMC
December 2020

Carob Seeds: Food Waste or Source of Bioactive Compounds?

Pharmaceutics 2020 Nov 13;12(11). Epub 2020 Nov 13.

Department of Drug Sciences, University of Catania, 95125 Catania, Italy.

(1) Background: For centuries, carob fruit has been used in the food field, while carob seeds have been mainly considered as food waste. Nowadays, there has been considerable attention toward the recovery of the waste plant matrices as possible sources of functional compounds with health properties. Therefore, our goal was to evaluate the health properties of carob seed extracts, and to study the effects of the ripening process on the chemical composition of the extracts. (2) Methods: After the mechanical separation of seeds from carob fruit, an ultrasound-assisted extraction (UAE) was performed to maximize and preserve the quality of bioactive compounds. Seed extracts were characterized by high-performance liquid chromatography (HPLC) and liquid chromatography/mass spectrometry (LC/MS) for the content of bioactive polyphenols, and were finally analyzed by oxygen radical absorbance capacity (ORAC), NO Scavenger (NO) and advanced glyoxidation end products (AGEs) assays, in order to estimate the antioxidant potential of the active compounds. (3) Results: Although both seed extracts of carob unripe (CAR-UR) and ripe (CAR-R) showed an interesting antioxidant activity, CAR-R had greater activity due to the procyanidins content. (4) Conclusions: Based on the obtained results, carob seed extracts could be regarded as interesting source of bioactive antioxidant compounds for a potential application in nutraceutical and food supplement fields.
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http://dx.doi.org/10.3390/pharmaceutics12111090DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7697644PMC
November 2020

Gene Silencing of Transferrin-1 Receptor as a Potential Therapeutic Target for Human Follicular and Anaplastic Thyroid Cancer.

Mol Ther Oncolytics 2020 Mar 21;16:197-206. Epub 2020 Jan 21.

Department of Biomedical and Biotechnological Sciences, University of Catania, Via S. Sofia 97, 95123 Catania, Italy.

Herein, we assess the gene expression changes activated in thyroid tumors through a computational approach, using the MapReduce algorithm. Through this predictive analysis, we identified the TfR1 gene as a critical mediator of thyroid tumor progression. Then, we investigated the effect of TfR1 gene silencing through small interfering RNA (siRNA) in the expression of extracellular signal-regulated kinase 1/2 (Erk1/2) pathway and c-Myc in human differentiated follicular and undifferentiated anaplastic thyroid cancer. The expression levels of cyclin D, p53, and p27, proteins involved in cell cycle progression, were also evaluated. The effect of TfR1 gene silencing through siRNA on the apoptotic pathway activation was also tested. Computational prediction and studies demonstrate that TfR1 plays a key role in thyroid cancer and that its downregulation was able to inhibit the ERK pathway, reducing also c-Myc expression, which blocks the cell cycle and activates the apoptotic pathway. We demonstrate that TfR1 plays a crucial role for a rapid and transient activation of the ERK signaling pathway, which induces a deregulation of genes involved in the aberrant accumulation of intracellular free iron and in drug resistance. We also suggest that TfR1 might represent an important target for thyroid cancer therapy.
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http://dx.doi.org/10.1016/j.omto.2020.01.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7033459PMC
March 2020

Dynamic changes in cytoskeleton proteins of olfactory ensheathing cells induced by radiofrequency electromagnetic fields.

J Exp Biol 2020 02 28;223(Pt 5). Epub 2020 Feb 28.

Department of Drug Sciences, Section of Biochemistry, University of Catania, 95125 Catania, Italy

Several evidences have suggested the ability of radiofrequency electromagnetic fields to influence biological systems, even if the action mechanisms are not well understood. There are few data on the effect of radiofrequency electromagnetic fields on self-renewal of neural progenitor cells. A particular glial type that shows characteristics of stem cells is olfactory ensheathing cells (OECs). Herein, we assessed the non-thermal effects induced on OECs through radiofrequency electromagnetic fields changing the envelope of the electromagnetic wave. Primary OEC cultures were exposed to continuous or amplitude-modulated 900 MHz electromagnetic fields, in the far-field condition and at different exposure times (10, 15, 20 min). The expression of OEC markers (S-100 and nestin), cytoskeletal proteins (GFAP and vimentin), apoptotic pathway activation by caspase-3 cleavage and cell viability were evaluated. Our results highlight that 20 min of exposure to continuous or amplitude-modulated 900 MHz electromagnetic fields induced a different and significant decrease in cell viability. In addition, according to the electromagnetic field waveform, diverse dynamic changes in the expression of the analysed markers in OECs and activation of the apoptotic pathway were observed. The data suggest that radiofrequency electromagnetic fields might play different and important roles in the self-renewal of OEC stem cells, which are involved in nervous system repair.
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http://dx.doi.org/10.1242/jeb.217190DOI Listing
February 2020

Antioxidant Activities of L. Leaf Extracts Determined in Cellular Models.

Foods 2019 Feb 8;8(2). Epub 2019 Feb 8.

Department of Drug Science, University of Catania, Viale Andrea Doria 6, 95125 Catania, Italy.

Several medicinal foods abound in traditional medicine with antioxidant potentials that could be of importance for the management of several diseases but with little or no scientific justification to substantiate their use. Thus, the objective of this study was the assessment of the antioxidant effect of two leave extracts of L. (SN), which is a medicinal plant member of the family, mainly used for soup preparation in different parts of the world. Then methanolic/water (80:20) (SN1) and water (SN2) leaves extracts were prepared. The total polyphenolic content and the concentration of phenolic acids and flavones compounds were determined. In order to verify whether examined extracts were able to restore the oxidative status, modified by glutamate in primary cultures of astrocytes, the study evaluated the glutathione levels, the intracellular oxidative stress, and the cytotoxicity of SN1 and SN2 extracts. Both extracts were able to quench the radical in an free cellular system and restore the oxidative status in primary cultures of rat astroglial cells exposed to glutamate. These extracts prevented the increase in glutamate uptake and inhibited glutamate excitotoxicity, which leads to cell damage and shows a notable antioxidant property.
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http://dx.doi.org/10.3390/foods8020063DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6406898PMC
February 2019

Nanotechnological Approach to Increase the Antioxidant and Cytotoxic Efficacy of Crocin and Crocetin.

Planta Med 2019 Feb 11;85(3):258-265. Epub 2018 Sep 11.

Department of Drug Sciences, University of Catania, Catania, Italy.

Crocin and crocetin are two interesting constituents of saffron () that possess important biological activities. Their use as therapeutic agents is strongly compromised by a scarce stability, poor absorption, and low bioavailability. Therefore, to improve these unfavorable features, the aim of the present work has been to apply a nanotechnological approach based on the formulation of solid lipid nanoparticles containing crocin and crocetin. Solid lipid nanoparticles were formulated according to crocin and crocetin chemical properties, using a variation of the quasi-emulsion solvent diffusion method to formulate crocin-solid lipid nanoparticles, while crocetin-solid lipid nanoparticles were prepared following the solvent diffusion method. Morphology and dimensional distribution of solid lipid nanoparticles have been characterized by differential scanning calorimetry and photon correlation spectroscopy, respectively, while the effect of drug incorporation versus time has been studied by Turbiscan technology. In order to verify the role of the nanotechnological approach on the biological activities of crocin and crocetin, the antioxidant and antiproliferative effects of these carotenoids once incorporated in lipid nanoparticles have been evaluated. For this aim, the oxygen radical absorbance capacity assay and the MTT test were used, respectively.The results pointed out the formulation of nanometric dispersions endowed with high homogeneity and stability, with an encapsulation efficiency ranging from 80 (crocetin-solid lipid nanoparticles) to 94% (crocin-crocetin). The oxygen radical absorbance capacity assay evidenced an interesting and prolonged antioxidant activity of crocin and crocetin once encapsulated in solid lipid nanoparticles, while the nanoencapsulation strategy showed a different mechanism in ameliorating the cytotoxic effect of these two substances.
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http://dx.doi.org/10.1055/a-0732-5757DOI Listing
February 2019

Effect of Some Growth Factors on Tissue Transglutaminase Overexpression Induced by β-Amyloid in Olfactory Ensheathing Cells.

Mol Neurobiol 2017 11 18;54(9):6785-6794. Epub 2016 Oct 18.

Department of Drug Sciences, Section of Biochemistry, University of Catania, Viale A. Doria 6, 95125, Catania, Italy.

Herein, we assessed in a particular glial cell type, called olfactory ensheathing cells (OECs), the effect of some growth factors (GFs) on tissue transglutaminase (TG2) overexpression induced by amyloid-beta (Aβ) with native full-length peptide 1-42 or by fragments, 25-35 or 35-25, as control. Previously, we demonstrated that TG2 overexpression induced by some stressors was down-regulated by GFs exposure in OECs. To monitor cell viability, an MTT test was used, while TG2 expression was examined using immunocytochemical and Western blot analysis. We also considered the involvement of the TG2-mediated apoptotic pathway. Vimentin expression was evaluated as well. Reactive oxygen species and reduced glutathione levels were utilized to test the oxidative intracellular status. Lactate dehydrogenase released into the medium, as a marker of necrotic cell death, was evaluated. We found that in OECs exposed to Aβ(1-42) or Aβ(25-35) for 24 h, TG2 expression increased, and we observed that the protein appeared prevalently localized in the cytosol. The pre-treatment with GFs, basic fibroblast growth factor (bFGF) or glial-derived neurotrophic factor (GDNF), down-regulated the TG2 level, which was prevalently limited to the nuclear compartment. Vimentin expression and caspase cleavage showed a significant enhancement in Aβ(1-42) and Aβ(25-35) exposed cells. The pre-treatment with bFGF or GDNF was able to restore the levels of the proteins to control values, and the intracellular oxidative status modified by the exposure to Aβ(1-42) or Aβ(25-35). Our data suggest that both bFGF or GDNF could be an innovative mechanism to contrast TG2 expression, which plays a key role in Alzheimer's disease.
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http://dx.doi.org/10.1007/s12035-016-0152-4DOI Listing
November 2017

Modulation of extracellular signal-related kinase, cyclin D1, glial fibrillary acidic protein, and vimentin expression in estradiol-pretreated astrocyte cultures treated with competence and progression growth factors.

J Neurosci Res 2015 Sep 6;93(9):1378-87. Epub 2015 Jun 6.

Department of Biomedical and Biotechnological Sciences, Section of Medical Biochemistry, University of Catania, Catania, Italy.

The present study seeks to elucidate the interactions between the "competence" growth factor basic fibroblast growth factor (bFGF) and/or estrogen 17β-estradiol and the "progression" growth factors epidermal growth factor (EGF), insulin-like growth factor-I (IGF-I), and insulin (INS) on DNA labeling and also cyclin D1, extracellular signal-related kinase 1/2 (ERK1/2), glial fibrillary acidic protein (GFAP), and vimentin expression in astroglial cultures under different experimental conditions. Pretreatment for 24 hr with bFGF and subsequent exposure for 36 hr to estradiol (E2 ) and EGF, IGF-I, or INS stimulated DNA labeling in the last 12 hr, especially when the cultures were treated with progression growth factors. bFGF pretreatment and subsequent treatment with E2 for 36 hr stimulated DNA labeling. The 36-hr E2 treatment alone did not significantly decrease DNA labeling, but contemporary addition of E2 with two or three growth factors stimulated DNA labeling remarkably. When E2 was coadded with growth factors, a significantly increased DNA labeling was observed, demonstrating an astroglial synergistic mitogenic effect evoked by contemporary treatment with growth factors in the presence of estrogens. Cyclin D1 expression was markedly increased when astrocyte cultures were pretreated for 36 hr with E2 and subsequently treated with two or three competence and progression growth factors. A highly significant increase of ERK1/2 expression was observed after all the treatments (EGF, bFGF, INS, IGF-I alone or in combination with two or three growth factors). GFAP and vimentin expression was markedly increased when the cultures were treated with two or three growth factors. In conclusion, our data demonstrate estradiol-growth factor cross-talk during astroglial cell proliferation and differentiation in culture.
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http://dx.doi.org/10.1002/jnr.23606DOI Listing
September 2015

Tissue transglutaminase expression during neural differentiation of human mesenchymal stem cells.

CNS Neurol Disord Drug Targets 2015 ;14(1):24-32

Department of Drug Sciences, Section of Biochemistry, University of Catania, Viale A. Doria 6, 95125, Catania, Italy.

Herein, we assessed the expression of transglutaminase-2 (TG2) during in vitro neural differentiation of human Mesenchymal Stem Cells (hMSCs) induced by some Growth Factors (GFs). The amount and distribution of mRNAs for some transglutaminase (TGs) isoforms (TG1, TG2, TG3, TG5) were also evaluated. In addition, we tested some neural lineage markers (Glial Acid Fibrillary Protein, GFAP; Neurofilament Protein, NF; Nestin; β-Tubulin III). A progressive increase of all neural markers during GFs neural differentiation of hMSCs was found. A significant overexpression of TG1 and TG2 mRNA was observed in undifferentiated hMSCs. GFs-treatment induced a progressive decrease of TG1 mRNA during hMSCs differentiation. A significant down-regulation of TG2 mRNA in 2 days in vitro (DIV) GFs-treated cells was observed. TG2 mRNA progressively increased during GFs hMSCs differentiation, reaching after 6 DIV of GFs-treatment of similar values to those observed in undifferentiated cells. TG3 mRNA levels were express at very low only in undifferentiated hMSCs, whereas TG5 mRNA was undetectable in undifferentiated and differentiated hMSCs. Immunocytochemical and Western blot analysis showed an overexpression of TG2 in undifferentiated hMSCs. A dramatic reduction of the protein levels in 2 DIV GFs-treated cells was observed. Its expression levels progressively increased during the differentiation of hMSCs with GFs, reaching after 6 DIV of the treatment similar values to those observed in undifferentiated cells. Our findings demonstrate the presence of multiple TGs in hMSCs during neural differentiation in vitro induced by GFs, and suggest that TG2 may be part of the downstream events associated to neural differentiation.
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http://dx.doi.org/10.2174/1871527314666150116111339DOI Listing
January 2016

Antioxidant properties of Berberis aetnensis C. Presl (Berberidaceae) roots extract and protective effects on astroglial cell cultures.

ScientificWorldJournal 2014 11;2014:315473. Epub 2014 Aug 11.

Department of Biomedical Sciences, Microbiology Section, University of Catania, Via Androne 81, 95125 Catania, Italy.

Berberis aetnensis C. Presl (Berberidaceae) is a bushy-spiny shrub common on Mount Etna (Sicily). We demonstrated that the alkaloid extract of roots of B. aetnensis C. Presl contains prevalently berberine and berbamine, possesses antimicrobial properties, and was able to counteract the upregulation evoked by glutamate of tissue transglutaminase in primary rat astroglial cell cultures. Until now, there are no reports regarding antioxidant properties of B. aetnensis C. Presl collected in Sicily. Air-dried, powdered roots of B. aetnensis C. Presl were extracted, identified, and quantified by HPLC. We assessed in cellular free system its effect on superoxide anion, radicals scavenging activity of antioxidants against free radicals like the 1,1-diphenyl-2-picrylhydrazyl radical, and the inhibition of xanthine oxidase activity. In primary rat astroglial cell cultures, exposed to glutamate, we evaluated the effect of the extract on glutathione levels and on intracellular production of reactive oxygen species generated by glutamate. The alkaloid extract of B. aetnensis C. Presl inhibited superoxide anion, restored to control values, the decrease of GSH levels, and the production of reactive oxygen species. Potent antioxidant activities of the alkaloid extract of roots of B. aetnensis C. Presl may be one of the mechanisms by which the extract is effective against health disorders associated to oxidative stress.
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http://dx.doi.org/10.1155/2014/315473DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4142662PMC
May 2015

FA-loaded lipid drug delivery systems: preparation, characterization and biological studies.

Eur J Pharm Sci 2014 Feb;52:12-20

The main purpose of this research was to prepare and to characterize ferulic acid-loaded nanostructured lipid carrier (FA-NLC) to evaluate the cytotoxic effect on human glioblastoma cancer U87MG cells. First of all, the influence of different materials on mean size and homogeneity of NLC prepared by a low energy organic solvent-free method was investigated. Technological characterization (encapsulation efficiency, mean particle size, homogeneity and in vitro release profile) was performed on the selected NLC in comparison to others lipid carriers, nanoemulsion and SLN. Furthermore, the thermal behavior of NLC and SLN was investigated using Differential Scanning Calorimetry (DSC) in order to evaluate their structure. Biological studies (MTT bioassay and caspase-3 cleavage) on the selected NLC showed no cytotoxic effects of the unloaded tested NLC. Besides, the effectiveness of FA-loaded NLC was higher compared to the free drug. Cells treated with FA or FA-loaded NLC showed a greater effect compared to idebenone (IDE) or IDE-loaded NLC, respectively. These results strongly support that FA-loaded NLC could be potentially used for the treatment of glioblastoma.
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http://dx.doi.org/10.1016/j.ejps.2013.10.003DOI Listing
February 2014

Expression of tissue transglutaminase on primary olfactory ensheathing cells cultures exposed to stress conditions.

Neurosci Res 2012 Apr 24;72(4):289-95. Epub 2011 Dec 24.

Department of Drug Sciences, University of Catania, Viale A. Doria 6, 95125 Catania, Italy.

Tissue transglutaminase (TG2), a multifunctional enzyme implicated in cellular proliferation and differentiation processes, plays a modulatory role in the cell response to stressors. Herein, we used olfactory ensheathing cells (OECs), representing an unusual population of glial cells to promote axonal regeneration and to provide trophic support, as well as to assess whether the effect of some Growth Factors (GFs), NGF, bFGF or GDNF, on TG2 overexpression induced by stress conditions, such as glutamate or lipopolysaccaride (LPS). Glial Fibrillary Acidic Protein (GFAP) and vimentin were used as markers of astroglial differentiation and cytoskeleton component, respectively. Glutamate or LPS treatment induced a particular increase of TG2 expression. A pre-treatment of the cells with the GFs restored the levels of the protein to that of untreated ones. Our results demonstrate that the treatment of OECs with the GFs was able to restore the OECs oxidative status as modified by stress, also counteracting TG2 overexpression. It suggests that, in OECs, TG2 modulation or inhibition induced by GFs might represent a therapeutic target to control the excitotoxicity and/or inflammation, which are involved in several acute and chronic brain diseases.
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http://dx.doi.org/10.1016/j.neures.2011.12.008DOI Listing
April 2012

In vitro evaluation of idebenone-loaded solid lipid nanoparticles for drug delivery to the brain.

Drug Dev Ind Pharm 2011 Jun 5;37(6):737-46. Epub 2011 Jan 5.

Department of Pharmaceutical Sciences, University of Catania, Catania, Italy.

Context: Solid lipid nanoparticles (SLN) are regarded as interesting drug delivery systems and their preparation techniques have gained a great deal of attention.

Objective: To evaluate the feasibility of preparing idebenone (IDE) loaded SLN from O/W microemulsions by the phase-inversion temperature (PIT) method. Since SLN have been proposed to improve drug delivery to the brain, IDE was chosen as model drug due to its activity in the treatment of neurodegenerative diseases.

Materials And Methods: Cetyl palmitate was used as solid lipid to prepare SLN containing two surfactant/cosurfactant mixtures, isoceteth-20/glyceryl oleate (SLN A) and ceteth-20/glyceryl oleate (SLN B) by the PIT method.

Results And Discussion: All the formulations tested showed a mean particle diameter ranging from 30 to 95 nm and a single peak in size distribution. Stability tests showed that SLN B were more stable than SLN A. IDE release was dependent both on the type of primary surfactant used and the amount of loaded drug. IDE-loaded SLN were effective in inhibiting 2,2'-azobis-(2-amidinopropane)dihydrochloride (APPH)-induced lactic dehydrogenase (LDH) release and reactive oxygen species (ROS) production in primary cultures of astrocytes obtained from rat cerebral cortex. It is noteworthy that SLN B2 (containing ceteth-20 as primary surfactant and 0.7% w/w IDE) were able to prevent entirely both the LDH release and ROS production induced by APPH.

Conclusion: The PIT method provided SLN with good technological properties. The tested SLN could be regarded as interesting carriers to overcome the blood brain barrier and increase the efficacy of the loaded drug.
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http://dx.doi.org/10.3109/03639045.2010.539231DOI Listing
June 2011

Effect of berberine and Berberis aetnensis C. Presl. alkaloid extract on glutamate-evoked tissue transglutaminase up-regulation in astroglial cell cultures.

Phytother Res 2011 Jun 17;25(6):816-20. Epub 2010 Nov 17.

Department of Biological Chemistry, Medical Chemistry and Molecular Biology, University of Catania, Catania, Italy.

Berberis aetnensis C. Presl. is a bushy-spiny shrub common on Mount Etna (Sicily, Italy), containing various alkaloids with several pharmacological properties. This study assessed the effect of berberine and of the alkaloid extract of B. aetnensis roots on the glutamate-evoked tissue transglutaminase (TG2) up-regulation in rat astrocyte primary cultures, used as an in vitro model of excitotoxicity. The findings show that the alkaloid extract of B. aetnensis roots consists mainly of berberine. Furthermore, berberine and the alkaloid extract of B. aetnensis roots were able to restore the oxidative status modified by glutamate and the levels of TG2 to control values. It was found that berberine or the alkaloid extract of B. aetnensis roots are able to ameliorate the excessive production of glutamate, protein misfolding and aggregation, mitochondrial fragmentation, and neurodegeneration. Thus, it is suggested that berberine and the alkaloid extract of B. aetnensis roots, may represent a natural therapeutic strategy in the neuropathological conditions associated with excitotoxicity.
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http://dx.doi.org/10.1002/ptr.3340DOI Listing
June 2011

Effects of liposomal encapsulation on the antioxidant activity of lipophilic prodrugs of idebenone.

J Liposome Res 2011 Mar 30;21(1):46-54. Epub 2010 Apr 30.

Dipartimento di Scienze Farmaceutiche, Università degli Studi di Catania, Catania, Italy.

Context: Increasing the lipophilicity and/or amphiphilicity of drugs is a potential strategy to improve loading and retention in lipid-based carriers, such as liposomes or lipid nanoparticles.

Objective: Idebenone (IDE), an antioxidant compound structurally related to coenzyme Q, or amphiphilic prodrugs of IDE with lipoamino acids, were loaded in neutral or negatively charged SUVET unilamellar liposomes to achieve a controlled release.

Methods: Technological properties of these systems in the presence of loaded drugs were evaluated in terms of vesicle size, homogeneity, and surface charge, as well as in vitro drug release. The effect of liposomal carrier on the in vitro antioxidant activity of the prodrugs was evaluated from using different biochemical assays on murine astrocyte cultures.

Results And Discussion: Although a good loading efficiency was obtained, liposomes were not able to release efficiently the encapsulated drugs, at least in the in vitro serum-free conditions used for the biological tests. However, in some cases, such as in the comet assay, encapsulation of IDE prodrugs in liposomes allowed for the improvement of their protective activity, compared to the free compounds, against the oxidative damage induced on cultured astrocytes.

Conclusions: Experimental in vitro data suggested that the high affinity shown by these lipophilic IDE derivatives for the liposomal carriers negatively affect their biological activity.
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http://dx.doi.org/10.3109/08982101003735996DOI Listing
March 2011

Reactive oxygen species levels and DNA fragmentation on astrocytes in primary culture after acute exposure to low intensity microwave electromagnetic field.

Neurosci Lett 2010 Mar 13;473(1):52-5. Epub 2010 Feb 13.

Dipartimento di Chimica Biologica, Chimica Medica e Biologia Molecolare, Università degli Studi di Catania, Viale A. Doria 6, I-95125 Catania, Italy.

The exposure of primary rat neocortical astroglial cell cultures to acute electromagnetic fields (EMF) in the microwave range was studied. Differentiated astroglial cell cultures at 14 days in vitro were exposed for 5, 10, or 20min to either 900MHz continuous waves or 900MHz waves modulated in amplitude at 50Hz using a sinusoidal waveform and 100% modulation index. The strength of the electric field (rms value) at the sample position was 10V/m. No change in cellular viability evaluated by MTT test and lactate dehydrogenase release was observed. A significant increase in ROS levels and DNA fragmentation was found only after exposure of the astrocytes to modulated EMF for 20min. No evident effects were detected when shorter time intervals or continuous waves were used. The irradiation conditions allowed the exclusion of any possible thermal effect. Our data demonstrate, for the first time, that even acute exposure to low intensity EMF induces ROS production and DNA fragmentation in astrocytes in primary cultures, which also represent the principal target of modulated EMF. Our findings also suggest the hypothesis that the effects could be due to hyperstimulation of the glutamate receptors, which play a crucial role in acute and chronic brain damage. Furthermore, the results show the importance of the amplitude modulation in the interaction between EMF and neocortical astrocytes.
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http://dx.doi.org/10.1016/j.neulet.2010.02.018DOI Listing
March 2010

Growth factors and steroid mediated regulation of cytoskeletal protein expression in serum-deprived primary astrocyte cultures.

Neurochem Res 2008 Dec 9;33(12):2593-600. Epub 2008 Jul 9.

Department of Chemical Sciences, Section of Biochemistry and Molecular Biology, University of Catania, viale Andrea Doria, 6, 95125, Catania, Italy.

In this research we aimed to investigate the interactions between growth factors (GFs) and dexamethasone (DEX) on cytoskeletal proteins GFAP and vimentin (VIM) expression under different experimental conditions. Condition I: 24 h pretreatment with bFGF, subsequent 72 h switching in serum-free medium (SFM) and final addition of GFs, alone or by two in the last 24 h, after a prolonged (60 h) DEX treatment. Condition II: 36 h pretreatment with DEX (with bFGF in the last 24 h), followed by SFM for 60 h and final addition for 24 h with growth factors alone or two of them together. Western blot analysis data showed a marked GFAP expression in cultures submitted to Condition I comparing results to untreated or treated controls. VIM expression was instead significantly reduced after GFs addition in the last 24 h of 60 h DEX treatment, respect to control DEX-pretreated ones. Referring data to untreated controls, VIM expression was significantly enhanced after GFs addition. GFAP showed also a significant increase in astrocytes submitted to Condition II, respect to untreated or treated control cultures. VIM expression was up and down regulated under Condition II. Collectively, our findings evidence an interactive dialogue between GFs and DEX in astroglial cultures, co-pretreated with DEX and bFGF, regulating cytoskeletal network under stressful conditions.
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http://dx.doi.org/10.1007/s11064-008-9767-9DOI Listing
December 2008

A cytoprotective role for the heme oxygenase-1/CO pathway during neural differentiation of human mesenchymal stem cells.

J Neurosci Res 2008 Jul;86(9):1927-35

Department of Surgical Research, Northwick Park Institute for Medical Research, Harrow, Middlesex, United Kingdom.

The inducible protein heme oxygenase-1 (HO-1) catalyzes the oxidation of heme to carbon monoxide (CO) and biliverdin, which play a concerted action in cytoprotection against oxidative stress and in the modulation of cell proliferation and differentiation. Here we report that both HO-1 expression and activity can be highly increased in undifferentiated human mesenchymal stem cells (MSCs) treated with hemin, a known HO-1 inducer. However, HO-1 mRNA and protein expression gradually decrease when MSCs undergo neural differentiation in vitro, making them extremely susceptible to glutamate-mediated cytotoxicity. A time course for HO-1 revealed that this protein is markedly down-regulated after 2 days and returns to control levels 6 days after differentiation. Treatment with glutamate (250 microM) after 2 days of neural differentiation resulted in a more pronounced lactate dehydrogenase release, a marker of cell injury, compared with undifferentiated cells. Notably, cells pretreated with hemin (50 microM) or compounds that release small amounts of CO (10 microM CORM-3 and CORM-A1) rendered cells more resistant to glutamate-induced toxicity; this effect was evident in both undifferentiated and differentiated MSCs. Our findings indicate that MSCs become more vulnerable to oxidative injury during the early stages of differentiation via mechanisms that involve a temporary inhibition of HO-1 expression. Thus, overexpression of HO-1 and CO-releasing molecules could provide a possible therapeutic strategy to improve cell viability during neural differentiation in applications that use stem cell technology.
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http://dx.doi.org/10.1002/jnr.21660DOI Listing
July 2008

Neurosteroid-growth factor cross-talk induces up and down regulation of GFAP and vimentin expression in serum free astrocyte cultures.

Ital J Biochem 2007 Dec;56(4):302-6

Department of Chemical Sciences, Section of Biochemistry and Molecular Biology, University of Catania, Italy.

In this research we aimed to investigate the interactions between growth factors (GFs) and dexamethasone (DEX) on cytoskeletal proteins GFAP and vimentin (VIM) expression under the following experimental condition: 24h pretreatment with bFGF, subsequent 72h switching in serum-free medium (SFM) and final addition of GFs, only one or more in the last 24h, after a prolonged (60h) DEX treatment. Western blot analysis data showed a marked GFAP expression in cultures submitted to our experimental condition comparing results to untreated or treated controls. In particular, the maximum level of GFAP expression is observed when EGF or INS or both together are added in a prolonged 60h DEX treatment. This finding well correlates with differentiative role played by glucocorticoids interacting with the "competence" factor bFGF and demonstrates as increased GFAP expression mostly depends on maturation, rather than proliferating status of astroglial cells in culture. VIM expression was instead significantly reduced after GFs addition in the last 24h of 60h DEX treatment, respect to control DEX-pretreated ones. Comparing the data to untreated controls, VIM expression was significantly enhanced after GFs addition. Collectively, our findings evidence an interactive effect between GFs and DEX in astroglial cultures, co-pretreated with DEX and bFGF, regulating cytoskeletal network under stressfull conditions.
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December 2007

Propofol inhibits caspase-3 in astroglial cells: role of heme oxygenase-1.

Curr Neurovasc Res 2005 Apr;2(2):141-8

Department of Biological Chemistry, Medical Chemistry and Molecular Biology, University of Catania, Italy.

Several lines of evidence have extensively demonstrated that peroxynitrite plays a pivotal role in Central Nervous System (CNS) injuries. The present study was aimed at elucidating the molecular mechanism by which propofol attenuates peroxynitrite-mediated injury in the brain. Primary cultured astroglial cells were incubated for 18 h with a known peroxynitrite donor (SIN-1,3 mM) in the presence or absence of propofol (40 microM, 80 microM and 160 microM). The protective effects of propofol were evaluated by MTT cytotoxicity assay, LDH release, and caspase-3 activation by Western blot analysis. Appropriate propofol concentrations (ranging from 40 microM to 160 microM) significantly increased HO-1 expression and attenuated SIN-1-mediated cytotoxicity and caspase-3 activation. The protective effects of propofol were mitigated by the addition of tin-mesoporphirin (SnMP), a potent inhibitor of HO activity. The addition of a specific synthetic inhibitor of NF-kappaB abolished propofol-mediated HO-1 induction, suggesting a possible role for this nuclear transcriptional factor in our experimental conditions. These findings indicate that propofol attenuates peroxynitrite-mediated apoptosis in astroglial cells, a property that may be relevant in both physiological and pathological processes in the CNS.
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http://dx.doi.org/10.2174/1567202053586820DOI Listing
April 2005

Enhancement of drug affinity for cell membranes by conjugation with lipoamino acids. I. Synthesis and biological evaluation of lipophilic conjugates of tranylcypromine.

Eur J Med Chem 2005 Nov 29;40(11):1074-9. Epub 2005 Aug 29.

Dipartimento di Scienze Farmaceutiche, Università degli Studi di Catania, Viale A. Doria, 6, I-95125 Catania, Italy.

Conjugation with lipoamino acids (LAAs) increases the lipophilicity of drug molecules. Because of their amphipatic nature, they also provide the conjugated drugs a 'membrane-like character', capable to facilitate their interaction with and penetration through cell membranes and biological barriers. To study such a feature, our aim is to collect experimental and computational data using a novel series of lipophilic conjugates between a model drug (tranylcypromine (TCP)) and LAA residues containing a short, a medium or a long alkyl side chain (C-4 to C-16), to provide a wide range of lipophilicity. For comparison, a corresponding set of amides of TCP with alkanoic or fatty acids was prepared and characterized. Their in vitro monoamine oxidase inhibitory activity also tested.
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http://dx.doi.org/10.1016/j.ejmech.2005.05.009DOI Listing
November 2005

Ochratoxin A-induced DNA damage in human fibroblast: protective effect of cyanidin 3-O-beta-d-glucoside.

J Nutr Biochem 2005 Jan;16(1):31-7

Department of Biochemistry, Medical Chemistry and Molecular Biology, University of Catania, Catania 95100, Italy.

Ochratoxin A (OTA), a mycotoxin produced by Aspergillus ochraceus and other moulds, has recently received growing attention because of its carcinogenic, teratogenic and nephrotoxic properties in both humans and farm animals. Nevertheless, with regard to the mechanism of toxicity, the data in the literature are inconclusive. The aim of our work was to verify in human fibroblasts treated with different OTA dosages the involvement of oxidative pathway in the damage mechanism of this mycotoxin and the possible protective effect exerted by cyanidin 3-O-beta-D-glucoside (C3G), an anthocyanin present in pigmented oranges, red wines, fruits and vegetables. The addition of OTA at 25 and 50 microM concentrations for 48 h determined only a slight but significant (P<.05) increase in radical oxygen species, whereas a substantial increase in their production was observed at longer exposure, in particular, when the fibroblasts were treated with 50 microM OTA for 72 h. Under the same experimental conditions, our data showed a significant (P<.05) increase in the rupture of cellular membrane and high damage to genomic DNA, evaluated by single-cell gel electrophoresis (comet assay), thus confirming the involvement of oxidative stress in the OTA genotoxicity in agreement with other studies. Diversely, mitochondrial functionality does not appear influenced by OTA treatment. C3G (0.125, 0.250 mM) added to the cells treated with 50 microM OTA significantly reduced free radical species production and prevented genomic DNA damage.
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http://dx.doi.org/10.1016/j.jnutbio.2004.05.005DOI Listing
January 2005

Propofol attenuates peroxynitrite-mediated DNA damage and apoptosis in cultured astrocytes: an alternative protective mechanism.

Anesthesiology 2004 Dec;101(6):1363-71

Department of Biological Chemistry, Medical Chemistry and Molecular Biology, Section of Biological Chemistry, University of Catania, Italy.

Background: The concentration of peroxynitrite in the brain increases after central nervous system injuries. The authors hypothesized that propofol, because of its particular chemical structure, mitigates the effects of peroxynitrite-mediated oxidative stress and apoptosis by the induction of heme oxygenase (HO)-1 in primary cultured astroglial cells.

Methods: Primary cultured astroglial cells were incubated for 18 h with a known peroxynitrite donor (3 mm SIN-1) in the presence or absence of propofol (40 microm, 80 microm, 160 microm, and 1 mm). The protective effects of propofol were evaluated by 3(4,5-dimethyl-thiazol-2-yl)2,5-diphenyl-tetrazolium bromide cytotoxicity assay, lactic dehydrogenase release, DNA ladderization by Comet assay, and caspase-3 activation by Western blot analysis.

Results: Appropriate propofol concentrations (ranging from 40 microm to 1 mm) significantly increased HO-1 expression and attenuated SIN-1-mediated DNA ladderization and caspase-3 activation. The protective effects of propofol were mitigated by the addition of tin mesoporphyrin, a potent inhibitor of HO activity. The addition of a specific synthetic inhibitor of nuclear factor kappaB abolished propofol-mediated HO-1 induction, suggesting a possible role of this nuclear transcriptional factor in our experimental conditions.

Conclusions: The antioxidant properties of propofol can be partially attributed to its scavenging effect on peroxynitrite as well as to its ability to increase HO-1 expression at higher concentrations, a property that might be relevant to neuroprotection during anesthesia.
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http://dx.doi.org/10.1097/00000542-200412000-00017DOI Listing
December 2004

Immunocytochemical localization and expression of heme oxygenase-1 in primary astroglial cell cultures during differentiation: effect of glutamate.

Biochem Biophys Res Commun 2004 Mar;315(2):517-24

Department of Biochemical, Physiological and Nutritional Sciences, University of Messina, Italy.

Heme oxygenase-1 (HO-1) catalyzes the rate-limiting step in heme degradation releasing iron, carbon monoxide (CO), and biliverdin. We investigated subcellular localization of HO-1 using confocal laser scanning microscopy (CLSM) and the expression by Western blot in primary astroglial cells during differentiation and after exposure to glutamate (100microM). CLSM analysis of immunostained HO-1 in cultured astroglial cells during differentiation showed an increase of fluorescence between 7 and 14 days and a decrease between 14 and 21, although HO-1 peaked at 14 days it remained at high levels. The distribution of HO-1 protein undergoes modification in the various cellular compartments. Furthermore, localization of the protein in untreated astrocytes at 7 days appeared prevalently localized in the cytosol and in the perinuclear region. In contrast, at 14 and 21 days, fluorescence detection suggests that HO-1 was present also in the nucleus, and in the nucleoli. Fluorescence intensity significantly increased in glutamate-treated astrocytes during all development stages and the protein appeared in the cytosol, in the nucleus and in the nucleoli. The involvement of AMPA/Ka receptors was studied in glutamate-treated astroglial cells at 14 days by the preincubation of the cells with GYKI 52466, a specific receptor inhibitor, of AMPA/Ka receptor demonstrating the involvement of these receptors. Western blot analysis of HO-1 confirmed the CLSM results. Our results demonstrate that changes in HO-1 protein expression and localization in primary cultured astroglial cells may be part of the underlying mechanisms involved in brain development as well as in neurodegenerative diseases.
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http://dx.doi.org/10.1016/j.bbrc.2004.01.090DOI Listing
March 2004

Nitric oxide-related toxicity in cultured astrocytes: effect of Bacopa monniera.

Life Sci 2003 Aug;73(12):1517-26

Department of Biological Chemistry, Medical Chemistry and Molecular Biology, University of Catania, v.le A. Doria 6, 95125 Catania, Italy.

There is growing evidence that high concentrations of nitric oxide (NO), generated by activated astrocytes, might be involved in a variety of neurodegenerative diseases, such as Alzheimer's disease, ischemia and epilepsy. It has recently been suggested that glial cells may produce NO under superoxide radical stimulation by enzyme-independent mechanism. This suggests that also natural antioxidants may have therapeutical relevance in neurodegenerative diseases. Studies of Bhattacharya et al. have evidenced that Bacopa monniera (BM) (family Scrophulariaceae), an Ayurvedic medicinal plant clinically used for memory enhancing, epilepsy, insomnia and as a mild sedative, is able to reduce the memory-dysfunction in rat models of Alzheimer's disease, but the molecular mechanisms of this action are yet to be determined. In the present study, we examined the effect of a methanolic extract of BM on toxicity induced by the nitric oxide donor, S-nitroso-N-acetyl-penicillamine (SNAP), in culture of purified rat astrocytes. Our results indicate that, after 18 h of treatment, SNAP induced an increase in the production of reactive species, but did not induce the rupture of cellular membrane. Conversely, this NO donor induced a fragmentation of genomic DNA compared to control astrocytes. The extract of BM inhibited the formation of reactive species and DNA damage in a dose dependent manner. This data supports the traditional use of BM and indicates that this medicinal plant has a therapeutic potential in treatment or prevention of neurological diseases.
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http://dx.doi.org/10.1016/s0024-3205(03)00476-4DOI Listing
August 2003