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1.
Mohammad-Panah Raha; Demolombe Sophie; Riochet David; Leblais Veronique; Loussouarn Gildas; Pollard Helene; Baro Isabelle; Escande Denis 《American journal of physiology. Cell physiology》1998,274(2):C310
We investigated whether high levels of expression of the cysticfibrosis transmembrane conductance regulator (CFTR) would alter thefunctional properties of newly synthesized recombinant proteins. COS-7,CFPAC-1, and A549 cells were intranuclearly injected with a Simianvirus 40-driven pECE-CFTR plasmid and assayed for halide permeabilityusing the6-methoxy-N-(3-sulfopropyl)quinolinium fluorescent probe. With increasing numbers of microinjected pECE-CFTR copies, the baseline permeability to halide dose dependently increased, and the response to adenosine 3',5'-cyclic monophosphate(cAMP) stimulation decreased. In cells hyperexpressing CFTR, the high level of halide permeability was reduced when a cell metabolism poisoning cocktail was applied to decrease intracellular ATP and, inversely, was increased by orthovanadate. In CFPAC-1 cellsinvestigated with the patch-clamp technique, CFTR hyperexpression ledto a time-independent nonrectifying chloride current that was notsensitive to cAMP stimulation. CFPAC-1 cells hyperexpressing CFTRexhibited no outward rectifying chloride current nor inward rectifyingpotassium current either spontaneously or under cAMP stimulation. Weconclude that hyperexpression of recombinant CFTR proteins modifiestheir properties inasmuch as 1) CFTRchannels are permanently activated and not susceptible to cAMPregulation and 2) they lose their capacity to regulate heterologous ionic channels. 相似文献
2.
Nina Bertaux-Skeirik Rui Feng Michael A. Schumacher Jing Li Maxime M. Mahe Amy C. Engevik Jose E. Javier Richard M. Peek Jr Karen Ottemann Veronique Orian-Rousseau Gregory P. Boivin Michael A. Helmrath Yana Zavros 《PLoS pathogens》2015,11(2)
The cytotoxin-associated gene (Cag) pathogenicity island is a strain-specific
constituent of Helicobacter pylori (H. pylori) that
augments cancer risk. CagA translocates into the cytoplasm where it stimulates cell
signaling through the interaction with tyrosine kinase c-Met receptor, leading
cellular proliferation. Identified as a potential gastric stem cell marker,
cluster-of-differentiation (CD) CD44 also acts as a co-receptor for c-Met, but
whether it plays a functional role in H. pylori-induced epithelial
proliferation is unknown. We tested the hypothesis that CD44 plays a functional role
in H. pylori-induced epithelial cell proliferation. To assay changes
in gastric epithelial cell proliferation in relation to the direct interaction with
H. pylori, human- and mouse-derived gastric organoids were
infected with the G27 H. pylori strain or a mutant G27 strain
bearing cagA deletion (∆CagA::cat). Epithelial proliferation
was quantified by EdU immunostaining. Phosphorylation of c-Met was analyzed by
immunoprecipitation followed by Western blot analysis for expression of CD44 and
CagA. H. pylori infection of both mouse- and human-derived gastric
organoids induced epithelial proliferation that correlated with c-Met
phosphorylation. CagA and CD44 co-immunoprecipitated with phosphorylated c-Met. The
formation of this complex did not occur in organoids infected with
∆CagA::cat. Epithelial proliferation in response to
H. pylori infection was lost in infected organoids derived from
CD44-deficient mouse stomachs. Human-derived fundic gastric organoids exhibited an
induction in proliferation when infected with H. pylorithat was not
seen in organoids pre-treated with a peptide inhibitor specific to CD44. In the
well-established Mongolian gerbil model of gastric cancer, animals treated with CD44
peptide inhibitor Pep1, resulted in the inhibition of H.
pylori-induced proliferation and associated atrophic gastritis. The current
study reports a unique approach to study H. pylori interaction with
the human gastric epithelium. Here, we show that CD44 plays a functional role in
H. pylori-induced epithelial cell proliferation. 相似文献
3.
Although diabetes has been identified as a major risk factor for atrial fibrillation, little is known about glucose metabolism in the healthy and diabetic atria. Glucose transport into the cell, the rate-limiting step of glucose utilization, is regulated by the Glucose Transporters (GLUTs). Although GLUT4 is the major isoform in the heart, GLUT8 has recently emerged as a novel cardiac isoform. We hypothesized that GLUT-4 and -8 translocation to the atrial cell surface will be regulated by insulin and impaired during insulin-dependent diabetes. GLUT protein content was measured by Western blotting in healthy cardiac myocytes and type 1 (streptozotocin-induced, T1Dx) diabetic rodents. Active cell surface GLUT content was measured using a biotinylated photolabeled assay in the perfused heart. In the healthy atria, insulin stimulation increased both GLUT-4 and -8 translocation to the cell surface (by 100% and 240%, respectively, P<0.05). Upon insulin stimulation, we reported an increase in Akt (Th308 and s473 sites) and AS160 phosphorylation, which was positively (P<0.05) correlated with GLUT4 protein content in the healthy atria. During diabetes, active cell surface GLUT-4 and -8 content was downregulated in the atria (by 70% and 90%, respectively, P<0.05). Akt and AS160 phosphorylation was not impaired in the diabetic atria, suggesting the presence of an intact insulin signaling pathway. This was confirmed by the rescued translocation of GLUT-4 and -8 to the atrial cell surface upon insulin stimulation in the atria of type 1 diabetic subjects. In conclusion, our data suggest that: 1) both GLUT-4 and -8 are insulin-sensitive in the healthy atria through an Akt/AS160 dependent pathway; 2) GLUT-4 and -8 trafficking is impaired in the diabetic atria and rescued by insulin treatment. Alterations in atrial glucose transport may induce perturbations in energy production, which may provide a metabolic substrate for atrial fibrillation during diabetes. 相似文献
4.
Elena Marinova Sandy P. Harrison Fran Bragg Simon Connor Veronique de Laet Suzanne A.G. Leroy Petra Mudie Juliana Atanassova Elissaveta Bozilova Hülya Caner Carlos Cordova Morteza Djamali Mariana Filipova‐Marinova Natalia Gerasimenko Susanne Jahns Katerina Kouli Ulrich Kotthoff Eliso Kvavadze Maria Lazarova Elena Novenko Elias Ramezani Astrid Röpke Lyudmila Shumilovskikh Ioan Tanţǎu Spassimir Tonkov 《Journal of Biogeography》2018,45(2):484-499
5.
6.
Patrizia Di Gennaro Linda Veronique Kazandjian Francesco Mezzetti Guido Sello 《Archives of microbiology》2013,195(4):269-278
This work reports the preparation of two recombinant strains each containing two enzymatic activities mutually expressed through regulated systems for production of functionalized epoxides in one-pot reactions. One strain was Pseudomonas putida PaW340, containing the gene coding for styrene monooxygenase (SMO) from Pseudomonas fluorescens ST under the auto-inducing Ptou promoter and the TouR regulator of Pseudomonas sp. OX1 and the gene coding for naphthalene dihydrodiol dehydrogenase (NDDH) from P. fluorescens N3 under the Ptac promoter inducible by IPTG. The second strain was Escherichia coli JM109, in which the expression of SMO was under the control of the Pnah promoter and the NahR regulator of P. fluorescens N3 inducible by salicylate, while the gene expressing NDDH was under the control of the Plac promoter inducible by IPTG. SMO and NDDH activities were tested in bioconversion experiments using cinnamyl alcohol as reference substrate. The application that we selected is one example of the sequential use of the two enzymatic activities which require a temporal control of the expression of both genes. 相似文献
7.
Andreia Barateiro Veronique E. Miron Sofia D. Santos João B. Relvas Adelaide Fernandes Charles ffrench-Constant Dora Brites 《Molecular neurobiology》2013,47(2):632-644
High levels of serum unconjugated bilirubin (UCB) in newborns are associated with axonal damage and glial reactivity that may contribute to subsequent neurologic injury and encephalopathy (kernicterus). Impairments in myelination and white matter damage were observed at autopsy in kernicteric infants. We have recently reported that UCB reduces oligodendrocyte progenitor cell (OPC) survival in a pure OPC in vitro proliferative culture. Here, we hypothesized that neonatal hyperbilirubinemia may also impair oligodendrocyte (OL) maturation and myelination. We used an experimental model of hyperbilirubinemia that has been shown to mimic the pathophysiological conditions leading to brain dysfunction by unbound (free) UCB. Using primary cultures of OL, we demonstrated that UCB delays cell differentiation by increasing the OPC number and reducing the number of mature OL. This finding was combined with a downregulation of Olig1 mRNA levels and upregulation of Olig2 mRNA levels. Addition of UCB, prior to or during differentiation, impaired OL morphological maturation, extension of processes and cell diameter. Both conditions reduced active guanosine triphosphate (GTP)-bound Rac1 fraction. In myelinating co-cultures of dorsal root ganglia neurons and OL, UCB treatment prior to the onset of myelination decreased oligodendroglial differentiation and the number of myelinating OL, also observed when UCB was added after the onset of myelination. In both circumstances, UCB decreased the number of myelin internodes per OL, as well as the myelin internode length. Our studies demonstrate that increased concentrations of UCB compromise myelinogenesis, thereby elucidating a potential deleterious consequence of elevated UCB. 相似文献
8.
Jérémy Jabiol Andreas Bruder Mark O. Gessner Marika Makkonen Brendan G. McKie Edwin T.H.M. Peeters Veronique C.A. Vos Eric Chauvet 《Fungal Ecology》2013,6(5):439-448
Information about the global distribution of aquatic hyphomycetes is scarce, despite the primary importance of these fungi in stream ecosystem functioning. In particular, the relationship between their diversity and latitude remains unclear, due to a lack of coordinated surveys across broad latitudinal ranges. This study is a first report on latitudinal patterns of aquatic hyphomycete diversity associated with native leaf-litter species in five streams located along a gradient extending from the subarctic to the tropics. Exposure of leaf litter in mesh bags of three different mesh sizes facilitated assessing the effects of including or excluding different size-classes of litter-consuming invertebrates. Aquatic hyphomycete evenness was notably constant across all sites, whereas species richness and diversity, expressed as the Hill number, reached a maximum at mid-latitudes (Mediterranean and temperate streams). These latitudinal patterns were consistent across litter species, despite a notable influence of litter identity on fungal communities at the local scale. As a result, the bell-shaped distribution of species richness and Hill diversity deviated markedly from the latitudinal patterns of most other groups of organisms. Differences in the body-size distribution of invertebrate communities colonizing the leaves had no effect on aquatic hyphomycete species richness, Hill diversity or evenness, but invertebrates could still influence fungal communities by depleting litter, an effect that was not captured by the design of our experiment. 相似文献
9.
10.
Barry E. Kennedy Veronique G. LeBlanc Tiffany M. Mailman Debra Fice Ian Burton Tobias K. Karakach Barbara Karten 《PloS one》2013,8(12)
Niemann-Pick Type C (NPC) disease is an autosomal recessive neurodegenerative disorder caused in most cases by mutations in the NPC1 gene. NPC1-deficiency is characterized by late endosomal accumulation of cholesterol, impaired cholesterol homeostasis, and a broad range of other cellular abnormalities. Although neuronal abnormalities and glial activation are observed in nearly all areas of the brain, the most severe consequence of NPC1-deficiency is a near complete loss of Purkinje neurons in the cerebellum. The link between cholesterol trafficking and NPC pathogenesis is not yet clear; however, increased oxidative stress in symptomatic NPC disease, increases in mitochondrial cholesterol, and alterations in autophagy/mitophagy suggest that mitochondria play a role in NPC disease pathology. Alterations in mitochondrial function affect energy and neurotransmitter metabolism, and are particularly harmful to the central nervous system. To investigate early metabolic alterations that could affect NPC disease progression, we performed metabolomics analyses of different brain regions from age-matched wildtype and Npc1
-/- mice at pre-symptomatic, early symptomatic and late stage disease by 1H-NMR spectroscopy. Metabolic profiling revealed markedly increased lactate and decreased acetate/acetyl-CoA levels in Npc1
-/- cerebellum and cerebral cortex at all ages. Protein and gene expression analyses indicated a pre-symptomatic deficiency in the oxidative decarboxylation of pyruvate to acetyl-CoA, and an upregulation of glycolytic gene expression at the early symptomatic stage. We also observed a pre-symptomatic increase in several indicators of oxidative stress and antioxidant response systems in Npc1
-/- cerebellum. Our findings suggest that energy metabolism and oxidative stress may present additional therapeutic targets in NPC disease, especially if intervention can be started at an early stage of the disease. 相似文献