Search results for "programme"
showing 10 items of 874 documents
Down-regulation of Glutathione and Bcl-2 Synthesis in Mouse B16 Melanoma Cells Avoids Their Survival during Interaction with the Vascular Endothelium
2003
B16 melanoma (B16M) cells with high GSH content show high metastatic activity. However, the molecular mechanisms linking GSH to metastatic cell survival are unclear. The possible relationship between GSH and the ability of Bcl-2 to prevent cell death was studied in B16M cells with high (F10) and low (F1) metastatic potential. Analysis of a Bcl-2 family of genes revealed that B16M-F10 cells, as compared with B16M-F1 cells, overexpressed preferentially Bcl-2 (approximately 5.7-fold). Hepatic sinusoidal endothelium-induced B16M-F10 cytotoxicity in vitro increased from approximately 19% (controls) to approximately 97% in GSH-depleted B16M-F10 cells treated with an antisense Bcl-2 oligodeoxynucl…
Molecular mechanisms of Id2 down-regulation in rat liver after acetaminophen overdose. Protection by N-acetyl-L-cysteine.
2010
Id2 is a pleiotropic protein whose function depends on its expression levels. Id2-deficient cells show increased cell death. This study explored the molecular mechanisms for the modulation of Id2 expression elicited by GSH and oxidative stress in the liver of acetaminophen (APAP)-intoxicated rats. APAP-overdose induced GSH depletion, Id2 promoter hypoacetylation, RNApol-II released and, therefore, Id2 down-regulation. Id2 expression depends on c-Myc binding to its promoter. APAP-overdose decreased c-Myc content and binding to Id2 promoter. Reduction of c-Myc was not accompanied by decreased c-myc mRNA, suggesting a mechanism dependent on protein stability. Administration of N-acetyl-cystein…
2-Hydroxyoleate, a nontoxic membrane binding anticancer drug, induces glioma cell differentiation and autophagy
2012
Despite recent advances in the development of new cancer therapies, the treatment options for glioma remain limited, and the survival rate of patients has changed little over the past three decades. Here, we show that 2-hydroxyoleic acid (2OHOA) induces differentiation and autophagy of human glioma cells. Compared to the current reference drug for this condition, temozolomide (TMZ), 2OHOA combated glioma more efficiently and, unlike TMZ, tumor relapse was not observed following 2OHOA treatment. The novel mechanism of action of 2OHOA is associated with important changes in membrane-lipid composition, primarily a recovery of sphingomyelin (SM) levels, which is markedly low in glioma cells bef…
Beneficial effect of dipyridyl, a liposoluble iron chelator against focal cerebral ischemia: In vivo and in vitro evidence of protection of cerebral …
2007
Whereas iron chelators were shown to induce neuroprotection against brain injury, the effect of iron chelators on ischemia-induced damage of cerebral endothelium is largely unknown. Our objective was to explore the endothelioprotective effect of the lipophilic iron chelator dipyridyl (DP) (i) in vitro on the death of cerebral endothelial cells (CECs) subjected to intracellular iron loading and (ii) in vivo on the ischemia-induced blood-brain barrier (BBB) disruption. When given shortly after iron exposure or brain ischemia, DP prevented the death of CECs and diminished BBB disruption, respectively, whereas a delayed administration of DP was associated with a lower CECs protection. Interesti…
Bcl-2 and Mn-SOD antisense oligodeoxynucleotides and a glutamine-enriched diet facilitate elimination of highly resistant B16 melanoma cells by tumor…
2005
Mitochondrial glutathione (mtGSH) depletion increases sensitivity of Bcl-2-overexpressing B16 melanoma (B16M)-F10 cells (high metastatic potential) to tumor necrosis factor-alpha (TNF-alpha)-induced oxidative stress and death in vitro. In vivo, mtGSH depletion in B16M-F10 cells was achieved by feeding mice (where the B16M-F10 grew as a solid tumor in the footpad) with an L-glutamine (L-Gln)-enriched diet, which promoted in the tumor cells an increase in glutaminase activity, accumulation of cytosolic L-glutamate, and competitive inhibition of GSH transport into mitochondria. L-Gln-adapted B16M-F10 cells, isolated using anti-Met-72 monoclonal antibodies and flow cytometry-coupled cell sortin…
Proneurotrophin Binding to P75 Neurotrophin Receptor (P75ntr) Is Essential for Brain Lesion Formation and Functional Impairment after Experimental Tr…
2015
Traumatic brain injury (TBI) initiates an excessive mediator release of e.g. neurotrophins, which promote neuronal survival, differentiation, and modulate synaptic plasticity. Paradoxically, mature forms of neurotrophins promote neuronal survival, whereas unprocessed forms of neurotrophins induce cell death through p75 neurotrophin receptor (p75NTR) signaling. p75NTR is widely expressed during synaptogenesis and is subsequently downregulated in adulthood. Repair mechanisms after acute cerebral insults can reactivate its expression. Therefore, the influence of p75NTR on secondary brain damage was addressed. mRNA levels of p75NTR and its ligands were quantified in brain tissue up to 7 days af…
Citrus limon-derived nanovesicles inhibit cancer cell proliferation and suppress CML xenograft growth by inducing TRAIL-mediated cell death
2015
// Stefania Raimondo 1 , Flores Naselli 1 , Simona Fontana 1 , Francesca Monteleone 1 , Alessia Lo Dico 1 , Laura Saieva 1 , Giovanni Zito 2 , Anna Flugy 1 , Mauro Manno 3 , Maria Antonietta Di Bella 1 , Giacomo De Leo 1 , Riccardo Alessandro 1 1 Dipartimento di Biopatologia e Biotecnologie Mediche, Universita degli Studi di Palermo, sezione di Biologia e Genetica, Palermo, Italy 2 Laboratorio di Ingegneria Tissutale – Piattaforme Innovative per l’Ingegneria Tissutale (PON01–00829), Istituto Ortopedico Rizzoli, Palermo, Italy 3 Istituto di Biofisica, Consiglio Nazionale delle Ricerche, Palermo, Italy Correspondence to: Riccardo Alessandro, e-mail: riccardo.alessandro@unipa.it Keywords: canc…
Occurrence of Retinal Ganglion Cell Loss via Autophagy and Apoptotic Pathways in an Autoimmune Glaucoma Model
2020
In glaucoma, an apoptotic death of retinal ganglion cells (RGCs) has been shown. However, little is known about other cell death mechanisms, like autophagy or necrosis. Therefore, we investigated these mechanisms in addition to antibody deposits in an experimental autoimmune glaucoma model.Rats were immunized with a retinal ganglion cell-layer homogenate (RGA), while controls received sodium chloride. Untreated rats served as natїve group. After seven weeks, retinal cross-sections were stained with antibodies against RGCs (Brn-3a), apoptosis (cleaved caspase 2, cleaved caspase 3 as well as caspase 3, 8, and 9), autophagy (LC3BII and LAMP1), and necrosis (RIPK3) followed by cell counts. Auto…
Naturalistic study on the usage of smartphone applications among Finnish drivers
2018
We present results from a naturalistic study that tracked how Finnish drivers use their smartphones while on the move. We monitored 30 heavy in-car smartphone users in Finland during June–September 2016, recording the times that they used their phones, the application used at the time of touch (calls excluded), the location and driving speed. Touches per time unit were used as a proxy for estimating visual-manual distraction due to visual-manual tasks. Our data set allows the determining of whether drivers use their phones differently on varying road types (highway, main road, local rural road, urban road). We found that the road type has an effect on phone use but the effect is contrary to…
Increase in Bcl-2 phosphorylation and reduced levels of BH3-only Bcl-2 family proteins in kainic acid-mediated neuronal death in the rat brain.
2003
Kainic acid induces excitotoxicity and nerve cell degeneration in vulnerable regions of rat brain, most markedly in hippocampus and amygdala. Part of the cell death following kainic acid is apoptotic as shown by caspase 3 activation and chromatin condensation. Here we have studied the regulation of pro- and anti-apoptotic proteins belonging to the Bcl-2 family in rat hippocampus and amygdala by kainic acid in relationship to ensuing neuronal death. The pro-apoptotic protein Bax was up-regulated in hippocampus 6 h after kainic acid administration. The increase in Bax was followed by the appearance of TdT-mediated dUTP nick end labelling-positive cells which were prominent at 24 h. Immunohist…