Search results for "Intracellular"
showing 10 items of 821 documents
Congenital secretory diarrhoea caused by activating germline mutations in GUCY2C
2016
Objective Congenital sodium diarrhoea (CSD) refers to a form of secretory diarrhoea with intrauterine onset and high faecal losses of sodium without congenital malformations. The molecular basis for CSD remains unknown. We clinically characterised a cohort of infants with CSD and set out to identify disease-causing mutations by genome-wide genetic testing. Design We performed whole-exome sequencing and chromosomal microarray analyses in 4 unrelated patients, followed by confirmatory Sanger sequencing of the likely disease-causing mutations in patients and in their family members, followed by functional studies. Results We identified novel de novo missense mutations in GUCY2C, the gene encod…
Relevance of Multidrug Resistance Proteins on the Clinical Efficacy of Cancer Therapy
2005
Variations in drug uptake and efflux, as well as changes in intracellular drug entrapment and distribution may represent important resistance mechanisms to cancer therapy. A variety of ATP binding cassette transporters (ABC) localised in multiple cell membranes is implied in those phenomena, representing a mechanism of protection of cells against xenobiotics. Many cancer cell lines over express some ABC transporters, especially p-glycoprotein, MRP1 and BCRP. This over expression is related to worse cancer treatment outcome and, in some cases, reduced overall survival of cancer patients. This paper reviews the location and physiological role of the three transporters mentioned and also descr…
Intracellular retention of ABL kinase inhibitors determines commitment to apoptosis in CML cells
2012
PLoS one 7(7), e40853 (2012). doi:10.1371/journal.pone.0040853
PED Mediates AKT-Dependent Chemoresistance in Human Breast Cancer Cells
2005
Abstract Killing of tumor cells by cytotoxic therapies, such as chemotherapy or gamma-irradiation, is predominantly mediated by the activation of apoptotic pathways. Refractoriness to anticancer therapy is often due to a failure in the apoptotic pathway. The mechanisms that control the balance between survival and cell death in cancer cells are still largely unknown. Tumor cells have been shown to evade death signals through an increase in the expression of antiapoptotic molecules or loss of proapoptotic factors. We aimed to study the involvement of PED, a molecule with a broad antiapoptotic action, in human breast cancer cell resistance to chemotherapeutic drugs–induced cell death. We show…
Cell-cell recognition system in gorgonians: description of the basic mechanism
1983
The dissociation of the gorgonian Eunicella cavolinii (Koch) into single cells was successfully accomplished. These cells readily formed aggregates of a size of 2 100 μm during incubation in roller tubes; no aggregate formation was observed in non-rotating Petri dishes. The formation of aggregates was not influenced by Ca++, urea or trypsin; it was also independent of temperature (4° to 30°C) and pH (5.5–9.0). The intercellular material of the gorgonian contains a galactose-specific lectin, as determined by double diffusion experiments and haemagglutination inhibition experiments using a series of galactoglycoconjugates. This lectin converted the aggregation-susceptible cells to aggregation…
Studies on heat shock proteins in sea urchin development
1999
Work on stress proteins in sea urchin embryos carried out over the last 20 years is reviewed and the following major results are described. Entire sea urchin embryos, if subjected to a rise in temperature at any postblastular stage undergo a wave of heat shock protein (hsp) synthesis and survive. If subjected to the same rise between fertilization and blastula formation, they are not yet able to synthesize hsp and die. Four clones coding for the major hsp, hsp70, have been isolated and sequenced; evidence for the existence of a heat shock factor has been provided, and a mechanism for the developmental regulation of hsp synthesis discussed. Intra- embryonic and intracellular hsp location has…
Sea urchin embryos as an in vivo model for the assessment of manganese toxicity: developmental and stress response effects.
2009
In the marine environment increasing concentrations of bio-available compounds often result from anthropogenic activities. Among metal ions, manganese represents a new emergent factor in environmental contamination. Here, we studied the effects of manganese on Paracentrotus lividus sea urchin embryos using biological and biochemical approaches for the analysis of impact on development, tissue accumulation and stress markers. Embryos were continuously exposed from fertilization to manganese at concentrations ranging from 1.0 to 61.6 mg l(-1), monitored for developmental abnormalities at 48 h after fertilization, and used for atomic spectrometric analysis at various times from 6 to 72 h. We f…
Cadmium induces an apoptotic response in sea urchin embryos.
2007
Cadmium is a heavy metal toxic for living organisms even at low concentrations. It does not have any biological role, and since it is a permanent metal ion, it is accumulated by many organisms. In the present paper we have studied the apoptotic effects of continuous exposure to subacute/sublethal cadmium concentrations on a model system: Paracentrotus lividus embryos. We demonstrated, by atomic absorption spectrometry, that the intracellular amount of metal increased during exposure time. We found, using terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assay, that long treatments with cadmium triggered a severe DNA fragmentation. We demonstrated, by immunocytochemistry …
Astrocytes of the murine model for Down Syndrome Ts65Dn display reduced intracellular ionic zinc.
2014
Zinc is an essential trace element that is critical for a large number of structural proteins, enzymatic processes and transcription factors. In the brain, zinc ions are involved in synaptic transmission. The homeostasis of zinc is crucial for cell survival and function, and cells have developed a wide variety of systems to control zinc concentration. Alterations in free zinc concentration have been related with brain dysfunction. Down Syndrome individuals present alterations in free zinc concentration and in some of the proteins related with zinc homeostasis. We have analyzed the amount of free zinc and the zinc chelating protein metallothionein 3 in the astrocytes using primary cultures o…
Ethanol reduces zincosome formation in cultured astrocytes.
2010
Aims Zinc is an ion that participates in basic cellular and tissular functions. Zinc deficiency is present in many physiological and health problems affecting most body organs, including the brain. Among the circumstances involved in zinc deficiency, ethanol consumption is probably one of the most frequent. A dietary zinc supplement has been proposed as possibly being an efficient method to palliate zinc deficiency. Astrocytes form part of the hematoencephalic barrier, and they are apparently implicated in the homeostasis of the neuronal medium. In this work, we analyze the effect of ethanol on extracellular zinc management by rat astrocytes in culture. Methods Intracellular levels of 'free…