Search results for "Small Interfering"
showing 10 items of 249 documents
NF-κB protects Behçet's disease T cells against CD95-induced apoptosis up-regulating antiapoptotic proteins
2005
Objective To determine whether prolongation of the inflammatory reaction in patients with Behcet's disease (BD) is related to apoptosis resistance and is associated with the up-regulation of antiapoptotic factors. Methods The percentage of cell death was evaluated by flow cytometry in peripheral blood mononuclear cells from 35 patients with BD and 30 healthy volunteers. The expression levels of antiapoptotic factors and NF-κB regulatory proteins were measured using Western blotting and immunohistochemical analyses. To down-regulate NF-κB nuclear translocation, BD T lymphocytes were exposed in vitro to thalidomide and subjected to transfection with NF-κB small interfering RNA. Results Althou…
Fibroblast Growth Factor Receptor 1– 5-Hydroxytryptamine 1A Heteroreceptor Complexes and Their Enhancement of Hippocampal Plasticity
2011
Background The hippocampus and its 5-hydroxytryptamine transmission plays an important role in depression related to its involvement in limbic circuit plasticity. Methods The analysis was made with bioluminescence resonance energy transfer, co-immunoprecipitation, in situ proximity ligation assay, binding assay, in cell western and the forced swim test. Results Using bioluminescence resonance energy transfer analysis, fibroblast growth factor receptor 1 (FGFR1)-5-hydroxytryptamine 1A (5-HT1A) receptor complexes have been demonstrated and their specificity and agonist modulation characterized. Their presence based on co-immunoprecipitation and proximity ligation assay has also been indicated…
Amyloid-β toxicity and tau hyperphosphorylation are linked via RCAN1 in Alzheimer's disease.
2011
Amyloid-β peptide (Aβ) toxicity and tau hyperphosphorylation are hallmarks of Alzheimer’s disease (AD). How their molecular relationships may affect the etiology, progression, and severity of the disease, however, has not been elucidated. We now report that incubation of foetal rat cortical neurons with Aβ up-regulates expression of the Regulator of Calcineurin gene RCAN1, and this is mediated by Aβ-induced oxidative stress. Calcineurin (PPP3CA) is a serine-threonine phosphatase that dephosphorylates tau. RCAN1 proteins inhibit this phosphatase activity of calcineurin. Increased expression of RCAN1 also causes up-regulation of glycogen synthase kinase-3beta (GSK3β), a tau kinase. Thus, incr…
Knock-down of the oxysterol receptor LXRα impairs cholesterol efflux in human primary macrophages: lack of compensation by LXRβ activation.
2012
Liver X Receptors (LXRs) α and β are oxysterol-activated nuclear receptors involved in the control of lipid metabolism and inflammation. Pharmacological activation of LXR is promising in the treatment of atherosclerosis since it can promote cholesterol efflux from macrophages and prevent foam cell formation. However, the development of LXR agonists has been limited by undesirable side-effects such as hepatic steatosis mediated by LXRα activation. Therefore, it has been proposed that targeting LXRα activators to extrahepatic tissues or using LXRβ-specific activators could be used as alternative strategies. It is not clear whether these molecules will retain the full atheroprotective potentia…
Superoxide Flux in Endothelial Cells via the Chloride Channel-3 Mediates Intracellular Signaling
2007
Reactive oxygen species (ROS) have been implicated in both cell signaling and pathology. A major source of ROS in endothelial cells is NADPH oxidase, which generates superoxide (O2.−) on the extracellular side of the plasma membrane but can result in intracellular signaling. To study possible transmembrane flux of O2.−, pulmonary microvascular endothelial cells were preloaded with the O2.−-sensitive fluorophore hydroethidine (HE). Application of an extracellular bolus of O2.−resulted in rapid and concentration-dependent transient HE oxidation that was followed by a progressive and nonreversible increase in nuclear HE fluorescence. These fluorescence changes were inhibited by superoxide dism…
Involvement of PAR-4 in Cannabinoid-Dependent Sensitization of Osteosarcoma Cells to TRAIL-Induced Apoptosis
2014
The synthetic cannabinoid WIN 55,212-2 is a potent cannabinoid receptor agonist with anticancer potential. Experiments were performed to determine the effects of WIN on proliferation, cell cycle distribution, and programmed cell death in human osteosarcoma MG63 and Saos-2 cells. Results show that WIN induced G2/M cell cycle arrest, which was associated with the induction of the main markers of ER stress (GRP78, CHOP and TRB3). In treated cells we also observed the conversion of the cytosolic form of the autophagosome marker LC3-I into LC3-II (the lipidated form located on the autophagosome membrane) and the enhanced incorporation of monodansylcadaverine and acridine orange, two markers of t…
Recent advances in smart biotechnology: Hydrogels and nanocarriers for tailored bioactive molecules depot
2017
Over the past ten years, the global biopharmaceutical market has remarkably grown, with ten over the top twenty worldwide high performance medical treatment sales being biologics. Thus, biotech R&D (research and development) sector is becoming a key leading branch, with expanding revenues. Biotechnology offers considerable advantages compared to traditional therapeutic approaches, such as reducing side effects, specific treatments, higher patient compliance and therefore more effective treatments leading to lower healthcare costs. Within this sector, smart nanotechnology and colloidal self-assembling systems represent pivotal tools able to modulate the delivery of therapeutics. A comprehens…
Meox2/Tcf15 Heterodimers Program the Heart Capillary Endothelium for Cardiac Fatty Acid Uptake
2015
Background— Microvascular endothelium in different organs is specialized to fulfill the particular needs of parenchymal cells. However, specific information about heart capillary endothelial cells (ECs) is lacking. Methods and Results— Using microarray profiling on freshly isolated ECs from heart, brain, and liver, we revealed a genetic signature for microvascular heart ECs and identified Meox2/Tcf15 heterodimers as novel transcriptional determinants. This signature was largely shared with skeletal muscle and adipose tissue endothelium and was enriched in genes encoding fatty acid (FA) transport–related proteins. Using gain- and loss-of-function approaches, we showed that Meox2/Tcf15 media…
CD36 is involved in lycopene and lutein uptake by adipocytes and adipose tissue cultures
2011
International audience; Scope: Carotenoids are mainly stored in adipose tissue. However, nothing is known regarding the uptake of carotenoids by adipocytes. Thus, our study explored the mechanism by which lycopene and lutein, two major human plasma carotenoids, are transported. Methods and results: CD36 was a putative candidate for this uptake, 3T3-L1 cells were treated with sulfosuccinimidyl oleate, a CD36-specific inhibitor. sulfosuccinimidyl oleate-treated cells showed a significant decrease in both lycopene and lutein uptake as compared to control cells. Their uptake was also decreased by partial inhibition of CD36 expression using siRNA, whereas the overexpression of CD36 in Cos-1 cell…
MS4A12 is a colon-selective store-operated calcium channel promoting malignant cell processes.
2008
AbstractUsing a data mining approach for the discovery of new targets for antibody therapy of colon cancer, we identified MS4A12, a sequence homologue of CD20. We show that MS4A12 is a cell surface protein. Expression analysis and immunohistochemistry revealed MS4A12 to be a colonic epithelial cell lineage gene confined to the apical membrane of colonocytes with strict transcriptional repression in all other normal tissue types. Expression is maintained upon malignant transformation in 63% of colon cancers. Ca2+ flux analyses disclosed that MS4A12 is a novel component of store-operated Ca2+ entry in intestinal cells. Using RNAi-mediated gene silencing, we show that loss of MS4A12 in LoVo co…