Search results for "Intracellular"
showing 10 items of 821 documents
Inhibition of DNA methylation sensitizes glioblastoma for tumor necrosis factor-related apoptosis-inducing ligand-mediated destruction.
2005
AbstractLife expectancy of patients affected by glioblastoma multiforme is extremely low. The therapeutic use of tumor necrosis factor–related apoptosis-inducing ligand (TRAIL) has been proposed to treat this disease based on its ability to kill glioma cell lines in vitro and in vivo. Here, we show that, differently from glioma cell lines, glioblastoma multiforme tumors were resistant to TRAIL stimulation because they expressed low levels of caspase-8 and high levels of the death receptor inhibitor PED/PEA-15. Inhibition of methyltransferases by decitabine resulted in considerable up-regulation of TRAIL receptor-1 and caspase-8, down-regulation of PED/PEA-15, inhibition of cell growth, and …
Malignantly transformed non-parenchymal liver epithelial cells and transformed oval cells suppress the homotypical gap junctional intercellular commu…
1995
Isolated rat liver parenchymal cells (PC) were co-cultured with a non-parenchymal rat liver epithelial cell line (NEC) or with an oval cell line. The homotypical gap junctional intercellular communication (GJIC) between the liver PC was measured after microinjection of Lucifer Yellow by dye transfer. The rat liver PC were dye coupled between 87% and 100% for at least 1 week in both co-cultures, in contrast to PC In monoculture between which no dye coupling was left after 1 week. When liver PC were co-cultured with a transformed and tumorigenic NEC or with a transformed and tumorigenic oval cell line the homotypical GJIC between the liver PC was drastically decreased with culture time, and t…
Meta-Analysis of the INSIG2 Association with Obesity Including 74,345 Individuals: Does Heterogeneity of Estimates Relate to Study Design?
2009
The INSIG2 rs7566605 polymorphism was identified for obesity (BMI≥30 kg/m2) in one of the first genome-wide association studies, but replications were inconsistent. We collected statistics from 34 studies (n = 74,345), including general population (GP) studies, population-based studies with subjects selected for conditions related to a better health status (‘healthy population’, HP), and obesity studies (OB). We tested five hypotheses to explore potential sources of heterogeneity. The meta-analysis of 27 studies on Caucasian adults (n = 66,213) combining the different study designs did not support overall association of the CC-genotype with obesity, yielding an odds ratio (OR) of 1.05 (p-va…
Up-regulation of c-FLIPshort and reduction of activation-induced cell death in T-cells from patients with Type 1 diabetes
2004
AICD of T-cells is an efficient way of removing activated T-lymphocytes. In this study we investigated the molecular basis of AICD upon reactivation in peripheral T-lymphocytes from newly diagnosed T1DM patients and age-matched healthy controls. In an in vitro model system, PHA-stimulated T-cells, upon prolonged culture in IL-2, acquire a sensitive phenotype to Fas-mediated apoptosis. This phenomenon is less pronounced in T1DM T-cells. Moreover, the restimulation of activated T-cells via TCR/CD3 and/or via CD28 inhibits Fas-mediated apoptosis in T1DM in comparison to control T-cells. After Fas triggering, the generation of the active sub-units of caspase-8 is significantly reduced in T1DM T…
CONNEXIN43 GAP JUNCTION LEVELS DURING DEVELOPMENT OF THE THORACIC AORTA ARE TEMPORALLY CORRELATED WITH ELASTIC LAMINAE DEPOSITION AND INCREASED BLOOD…
1997
A characteristic property of the vascular smooth muscle cell is its ability to modulate between a contractile phenotype, responsible for control of vascular tone, through to a synthetic phenotype, capable of migration and synthesis of extracellular matrix molecules. Smooth muscle cells are coupled by gap junctions, the membrane structures which permit direct intercelluar passage of ions and small molecules, and which play a role both in electrical coupling and intercellular communication during patterning and development. We have previously found that connexin43 type gap junction expression is upregulated in the synthetic phenotype smooth muscle cell in vitro and during atherosclerotic plaq…
An experimental design for the controlled modulation of intracellular GSH levels in cultured hepatocytes
2006
This work proposes a practical experimental approach that allows the rapid in situ generation of a wide range of intracellular GSH concentrations in the intact hepatocyte under highly reproducible conditions. The strategy involves the use of diethyl maleate, a thiol-reactive electrophile that causes rapid and extensive GSH depletion, as well as GSH monoethylester, a GSH analogue that is readily taken up by cells and deesterified intracellularly to render GSH. For both agents, we have analyzed (i) the minimal exposure time required to produce a maximal and dose-related effect on intracellular GSH without altering hepatocyte viability or subsequent survival in culture, and (ii) the relative s…
Influence of intracellular convection on the oxygen release by human erythrocytes
1972
There is general agreement today that intracellular diffusive transport of HbO2 and O2 limits the rate of oxygen uptake or release by the blood in the exchange vessels. Recent hemorheological results have shown that the mammalian erythrocyte exhibits fluidity as its most unique rheological property: it can be deformed continuously and rapidly, shear and normal stresses can be transmitted to the interior of the cell where systems of laminar flow are induced. These mechanical properties lead to the question whether or not intracellular convection does take place in the erythrocyte and to what extent it plays a part in gas exchange. A method was developed which subjects oxygen-saturated soluti…
X-linked primary ciliary dyskinesia due to mutations in the cytoplasmic axonemal dynein assembly factor PIH1D3
2017
By moving essential body fluids and molecules, motile cilia and flagella govern respiratory mucociliary clearance, laterality determination and the transport of gametes and cerebrospinal fluid. Primary ciliary dyskinesia (PCD) is an autosomal recessive disorder frequently caused by non-assembly of dynein arm motors into cilia and flagella axonemes. Before their import into cilia and flagella, multi-subunit axonemal dynein arms are thought to be stabilized and pre-assembled in the cytoplasm through a DNAAF2–DNAAF4–HSP90 complex akin to the HSP90 co-chaperone R2TP complex. Here, we demonstrate that large genomic deletions as well as point mutations involving PIH1D3 are responsible for an X-li…
Molecular basis of endothelial dysfunction in sepsis.
2003
Sepsis is one of the major causes of mortality in critically ill patients and develops as a result of the host response to infection. A complex network of events is set into motion in the body by the infection and results in the pathogenesis of sepsis. This review article focuses on the molecular mechanisms and components involved in the pathogenesis of sepsis with a major emphasis on the endothelium. This includes sepsis-inducing bacterial components (e.g. endotoxins), cellular targets of these molecules and their responses, host reactions, intracellular and cytokine networks, individual susceptibility and new therapeutic targets in sepsis treatment.
Postnatal Deletion of Numb/Numblike Reveals Repair and Remodeling Capacity in the Subventricular Neurogenic Niche
2006
Neural stem cells are retained in the postnatal subventricular zone (SVZ), a specialized neurogenic niche with unique cytoarchitecture and cell-cell contacts. Although the SVZ stem cells continuously regenerate, how they and the niche respond to local changes is unclear. Here we generated nestin-creERtm transgenic mice with inducible Cre recombinase in the SVZ, and removed Numb/Numblike, key regulators of embryonic neurogenesis from postnatal SVZ progenitors and ependymal cells. This resulted in severe damage to brain lateral ventricle integrity, and identified previously unknown roles for Numb/Numblike in regulating ependymal wall integrity and SVZ neuroblast survival. Surprisingly, the ve…