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showing 10 items of 806 documents
Inhibition of stearoyl-CoA desaturase 1 expression induces CHOP-dependent cell death in human cancer cells.
2010
Background Cancer cells present a sustained de novo fatty acid synthesis with an increase of saturated and monounsaturated fatty acid (MUFA) production. This change in fatty acid metabolism is associated with overexpression of stearoyl-CoA desaturase 1 (Scd1), which catalyses the transformation of saturated fatty acids into monounsaturated fatty acids (e.g., oleic acid). Several reports demonstrated that inhibition of Scd1 led to the blocking of proliferation and induction of apoptosis in cancer cells. Nevertheless, mechanisms of cell death activation remain to be better understood. Principal Findings In this study, we demonstrated that Scd1 extinction by siRNA triggered abolition of de nov…
Inulin-Ethylenediamine Coated SPIONs Magnetoplexes: A Promising Tool for Improving siRNA Delivery.
2015
An inulin based polycation (Inu-EDA) has been synthesized by the grafting of ethylenediamine molecules onto inulin backbone. The obtained inulin copolymer has been though to coat SPIONs (IC-SPIONs) and obtain stable magnetoplexes by complexation of IC-SPIONs with a model duplexed siRNA, for improving oligonucleotide transfection efficiency.The physical-chemical characteristics of IC-SPIONs and IC-SPIONs/siRNA magnetoplexes have been investigated by scanning and transmission electron microscopies, dynamic light scattering, FT-IR and qualitative surface elementary analysis. Cell compatibility and internalization in vitro of IC-SPIONs have been evaluated by MTS and fluorescence microscopy resp…
The Functional Role of the Second NPXY Motif of the LRP1 β-Chain in Tissue-type Plasminogen Activator-mediated Activation of N-Methyl-D-aspartate Rec…
2008
The low density lipoprotein receptor-related protein 1 (LRP1) emerges to play fundamental roles in cellular signaling pathways in the brain. One of its prominent ligands is the serine proteinase tissue-type plasminogen activator (tPA), which has been shown to act as a key activator of neuronal mitogen-activated protein kinase pathways via the N-methyl-D-aspartate (NMDA) receptor. However, here we set out to examine whether LRP1 and the NMDA receptor might eventually act in a combined fashion to mediate tPA downstream signaling. By blocking tPA from binding to LRP1 using the receptor-associated protein, we were able to completely inhibit NMDA receptor activation. Additionally, inhibition of …
Changes in carnitine octanoyltransferase activity induce alteration in fatty acid metabolism
2011
The peroxisomal beta oxidation of very long chain fatty acids (VLCFA) leads to the formation of medium chain acyl-CoAs such as octanoyl-CoA. Today, it seems clear that the exit of shortened fatty acids produced by the peroxisomal beta oxidation requires their conversion into acyl-carnitine and the presence of the carnitine octanoyltransferase (CROT). Here, we describe the consequences of an overexpression and a knock down of the CROT gene in terms of mitochondrial and peroxisomal fatty acids metabolism in a model of hepatic cells. Our experiments showed that an increase in CROT activity induced a decrease in MCFA and VLCFA levels in the cell. These changes are accompanied by an increase in …
Role of adenylate kinase type 7 expression on cilia motility: possible link in primary ciliary dyskinesia.
2010
Background Adenylate kinase 7 (AK7) mediates the reaction 2ADP ↔ ATP + AMP, providing energy for the beating of cilia. A study recently showed that AK7 expression may be correlated with the primary ciliary dyskinesia (PCD) phenotype in mice. In this study, we characterized AK7 expression in vitro in an air–liquid interface (ALI) model and in middle nasal turbinate biopsy specimens from a cohort of patients with PCD to elucidate whether AK7 expression is correlated with ciliary malfunction. Methods AK7 expression was measured by real-time reverse-transcription polymerase chain reaction and Western blotting. In vitro differentiated nasal human epithelial cell siRNA experiments were performed …
A glial amino-acid transporter controls synapse strength and courtship in Drosophila
2008
1097-6256 (Print) Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't; Mate choice is an evolutionarily critical decision that requires the detection of multiple sex-specific signals followed by central integration of these signals to direct appropriate behavior. The mechanisms controlling mate choice remain poorly understood. Here, we show that the glial amino-acid transporter genderblind controls whether Drosophila melanogaster males will attempt to mate with other males. Genderblind (gb) mutant males showed no alteration in heterosexual courtship or copulation, but were attracted to normally unappealing male species-specific chemosensory cues. As a resul…
Mechanisms of ceramide-induced COX-2-dependent apoptosis in human ovarian cancer OVCAR-3 cells partially overlapped with resveratrol.
2013
Ceramide is a member of the sphingolipid family of bioactive molecules demonstrated to have profound, diverse biological activities. Ceramide is a potential chemotherapeutic agent via the induction of apoptosis. Exposure to ceramide activates extracellular-signal-regulated kinases (ERK)1/2- and p38 kinase-dependent apoptosis in human ovarian cancer OVCAR-3 cells, concomitant with an increase in the expression of COX-2 and p53 phosphorylation. Blockade of cyclooxygenase-2 (COX-2) activity by siRNA or NS398 correspondingly inhibited ceramide-induced p53 Ser-15 phosphorylation and apoptosis; thus COX-2 appears at the apex of the p38 kinase-mediated signaling cascade induced by ceramide. Induct…
From Spherical Mesopores to Worm-Shaped Mesopores : Morphology Transition in Titania–Polystyrene-b-poly(ethylene oxide) Composite Films with Increasi…
2013
A morphology transition from spherical mesopores to worm-shaped mesopores within titania block copolymer composite thin films has been observed by varying the sol–gel reaction time from 40 min to 48 h in the four-component templating system of polystyrene-$\mathit{b}$-poly(ethylene oxide) (PS-$\mathit{b}$-PEO), 1,4-dioxane, concentrated HCl, and titanium tetraisopropoxide (TTIP) with a PS-$\mathit{b}$-PEO mass concentration of 0.25 wt.-%. The impact of the sol–gel reaction time on the local structure, long-range lateral structure, and vertical structure of the as-prepared, calcined, and UV-degraded thin films as well as the structural changes in solution have been systematically investigate…
Toward Biopredictive Dissolution for Enteric Coated Dosage Forms
2016
The aim of this work was to develop a phosphate buffer based dissolution method for enteric-coated formulations with improved biopredictivity for fasted conditions. Two commercially available enteric-coated aspirin products were used as model formulations (Aspirin Protect 300 mg, and Walgreens Aspirin 325 mg). The disintegration performance of these products in a physiological 8 mM pH 6.5 bicarbonate buffer (representing the conditions in the proximal small intestine) was used as a standard to optimize the employed phosphate buffer molarity. To account for the fact that a pH and buffer molarity gradient exists along the small intestine, the introduction of such a gradient was proposed for p…
Gliadin, zonulin and gut permeabilità: effects on celiac and non-celiac intestinal mucosa and intestinal cell lines.
2006
Objective. Little is known about the interaction of gliadin with intestinal epithelial cells and the mechanism(s) through which gliadin crosses the intestinal epithelial barrier. We investigated whether gliadin has any immediate effect on zonulin release and signaling. Material and methods. Both ex vivo human small intestines and intestinal cell monolayers were exposed to gliadin, and zonulin release and changes in paracellular permeability were monitored in the presence and absence of zonulin antagonism. Zonulin binding, cytoskeletal rearrangement, and zonula occludens-1 (ZO-1) redistribution were evaluated by immunofluorescence microscopy. Tight junction occludin and ZO-1 gene expression …