Search results for "CASP"

Phosphodiesterase inhibition induces retinal degeneration, oxidative stress and inflammation in cone-enriched cultures of porcine retina.

2013

nherited retinal degenerations affecting both rod and cone photoreceptors constitute one of the causes 74 of incurable blindness in the developed world. Cyclic guanosine monophosphate (cGMP) is crucial in the 75 phototransduction and, mutations in genes related to its metabolism are responsible for different retinal 76 dystrophies. cGMP-degrading phosphodiesterase 6 (PDE6) mutations cause around 4e5% of the retinitis 77 pigmentosa, a rare form of retinal degeneration. The aim of this study was to evaluate whether phar- 78 macological PDE6 inhibition induced retinal degeneration in cone-enriched cultures of porcine retina 79 similar to that found in murine models. PDE6 inhibition was induced…

Red wine extract prevents neuronal apoptosis in vitro and reduces mortality of transgenic mice.

2007

In this work, we have investigated the effects of nutritional antioxidants as antidegenerative agents on glutamate-induced apoptosis in primary cultures of cerebellar granule neurons (CGNs). Glutamate-induced apoptosis is also associated with intracellular [Ca(2+)]i overload, generation of reactive oxygen species (ROS), depression of cell energy metabolism, cytochrome c release, and increase in caspase-3 activity. Pretreatment (3 h) with red wine extract (5 microg/mL) and ascorbic acid (30 microM) blocks glutamate-induced apoptosis in CGNs. In vivo experiments carried out on transgenic mice expressing the human mutated Cu, Zn superoxide dismutase (SOD1) G93A (mSOD1(G93A)) show that mice fed…

Parthenolide sensitizes hepatocellular carcinoma cells to trail by inducing the expression of death receptors through inhibition of STAT3 activation

2011

This article shows that HepG2, Hep3B, and SK-Hep1 cells, three lines of human hepatocellular carcinoma (HCC) cells, are resistant to apoptosis induced by tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). Parthenolide, a sesquiterpene lactone found in European feverfew, has been shown to exert both anti-inflammatory and anti-cancer activities. This article demonstrates that co-treatment with parthenolide and TRAIL-induced apoptosis with synergistic interactions in the three lines of HCC cells. In order to explain these effects we ascertained that parthenolide increased either at protein or mRNA level the total content of death receptors TRAIL-R1 and -R2 as well as their surfac…

Performance of the auxotrophic Saccharomyces cerevisiae BY4741 as host for the production of IL-1β in aerated fed-batch reactor: role of ACA suppleme…

2009

Abstract Background Saccharomyces cerevisiae BY4741 is an auxotrophic commonly used strain. In this work it has been used as host for the expression and secretion of human interleukin-1β (IL1β), using the cell wall protein Pir4 as fusion partner. To achieve high cell density and, consequently, high product yield, BY4741 [PIR4-IL1β] was cultured in an aerated fed-batch reactor, using a defined mineral medium supplemented with casamino acids as ACA (auxotrophy-complementing amino acid) source. Also the S. cerevisiae mutant BY4741 Δyca1 [PIR4-IL1β], carrying the deletion of the YCA1 gene coding for a caspase-like protein involved in the apoptotic response, was cultured in aerated fed-batch rea…

Synthetic lethal metabolic targeting of cellular senescence in cancer therapy.

2013

Activated oncogenes and anticancer chemotherapy induce cellular senescence, a terminal growth arrest of viable cells characterized by S-phase entry-blocking histone 3 lysine 9 trimethylation (H3K9me3). Although therapy-induced senescence (TIS) improves long-term outcomes, potentially harmful properties of senescent tumour cells make their quantitative elimination a therapeutic priority. Here we use the Eµ-myc transgenic mouse lymphoma model in which TIS depends on the H3K9 histone methyltransferase Suv39h1 to show the mechanism and therapeutic exploitation of senescence-related metabolic reprogramming in vitro and in vivo. After senescence-inducing chemotherapy, TIS-competent lymphomas but …

PROTEIN SECONDARY STRUCTURE PREDICTION: HOW TO IMPROVE ACCURACY BY INTEGRATION

2006

In this paper a technique to improve protein secondary structure prediction is proposed. The approach is based on the idea of combining the results of a set of prediction tools, choosing the most correct parts of each prediction. The correctness of the resulting prediction is measured referring to accuracy parameters used in several editions of CASP. Experimental evaluations validating the proposed approach are also reported.

IL PARTENOLIDE INDUCE MORTE CELLULARE CASPASI-INDIPENDENTE IN CELLULE DI OSTEOSARCOMA UMANO MG63

2011

Parthenolide induces caspase-independent cell death mediated by AIF in osteosarcoma and melanoma cells.

2012

Parthenolide, the major bioactive sesquiterpene lactone present in Feverfew (Tanacetum parthenium), has recently attracted considerable attention because of its complex pharmacological action involving anti-microbial, anti-inflammatory and anti-cancer effects. However, the mechanism of its cytotoxic effect on tumor cells still remains scarcely defined today. The aim of this study was to analyse the mechanism of parthenolide action on two lines of cancer cells, the human osteosarcoma MG63 and the melanoma SK-MEL-28 cells, on which parthenolide exerted its action inducing similar effects. Staining with Hoechst 33342 showed that parthenolide induced in the first phase of treatment (0-5 h) in m…

NOVEL ANTAGONISTS FOR AN Hsp60-BASED ANTICANCER CHAPERONOTHERAPY

2012

The Heat shock proteins (Hsps) are nowadays considered the most important cell chaperones, which result overexpressed in response to a number of cell stress stimuli.In tumor cells, when Hsp60 accumulates in the cytosol, without mitochondrial release, it exerts an anti-apoptotic effect, by inhibiting pro-caspase-3 (pC3) activation. In this context, our study aims to elucidate the structural details of the interaction between Hsp60 and pC3 and to design novel antagonists able to specifically block this interaction. The analysis of virtual screening results highlights the 4-(3-chloro-4-fluorophenylamino)- 6-[(1H-imidazol-4-yl-methyl)-3-carbonitrile-quinolines of type 1 and the N-{5-[1H-imidazo…

Expression of β-Endorphin and Caspase-9 in Orthodontically Treated Dental Pulp.

2009

Introduction. For several years, our histology laboratory has worked in co-operation with the Winchmore Hill Dental Practice studying the activity of Acetylcholinesterase and some neuropeptides (CGRP, Sub. P, Enkephalins, Endorphins)(1) in orthodontic treated human dental pulp to clarify force's action. It seems that recent data do not yet, fully elucidate the exact effects of the force applied on teeth. For this reason we are investigating whether the traction is involved in some cases of pulpal death. In this study we focused on the expression of Caspase-9 and β-Endorphine. Materials and Methods. The expression of the 2 peptides has been identified through immunohistochemistry assay: not …