Search results for "MESH: Signal Transduction"
showing 10 items of 11 documents
Immune Cell Toll-like Receptor 4 Mediates the Development of Obesity- and Endotoxemia-Associated Adipose Tissue Fibrosis
2014
International audience; Adipose tissue fibrosis development blocks adipocyte hypertrophy and favors ectopic lipid accumulation. Here, we show that adipose tissue fibrosis is associated with obesity and insulin resistance in humans and mice. Kinetic studies in C3H mice fed a high-fat diet show activation of macrophages and progression of fibrosis along with adipocyte metabolic dysfunction and death. Adipose tissue fibrosis is attenuated by macrophage depletion. Impairment of Toll-like receptor 4 signaling protects mice from obesity-induced fibrosis. The presence of a functional Toll-like receptor 4 on adipose tissue hematopoietic cells is necessary for the initiation of adipose tissue fibros…
Regulating TRAIL Receptor-Induced Cell Death at the Membrane: A Deadly Discussion
2011
Article Open access plus; International audience; The use of TRAIL/APO2L and monoclonal antibodies targeting TRAIL receptors for cancer therapy holds great promise, due to their ability to restore cancer cell sensitivity to apoptosis in association with conventional chemotherapeutic drugs in a large variety of tumors. TRAIL-induced cell death is tightly regulated right from the membrane and at the DISC (Death-Inducing Signaling Complex) level. The following patent and literature review aims to present and highlight recent findings of the deadly discussion that determines tumor cell fate upon TRAIL engagement.
S-nitrosylation of the death receptor fas promotes fas ligand-mediated apoptosis in cancer cells.
2011
International audience; BACKGROUND & AIMS: Fas belongs to the family of tumor necrosis factor receptors which induce apoptosis. Many cancer cells express Fas but do not undergo Fas-mediated apoptosis. Nitric oxide reverses this resistance by increasing levels of Fas at the plasma membrane. We studied the mechanisms by which NO affects Fas function. METHODS: Colon and mammary cancer cell lines were incubated with the NO donor glyceryl trinitrate or lipid A; S-nitrosylation of Fas was monitored using the biotin switch assay. Fas constructs that contained mutations at cysteine residues that prevent S-nitrosylation were used to investigate the involvement of S-nitrosylation in Fas-mediated cell…
Anti-inflammatory Lactobacillus rhamnosus CNCM I-3690 strain protects against oxidative stress and increases lifespan in Caenorhabditis elegans.
2012
International audience; Numerous studies have shown that resistance to oxidative stress is crucial to stay healthy and to reduce the adverse effects of aging. Accordingly, nutritional interventions using antioxidant food-grade compounds or food products are currently an interesting option to help improve health and quality of life in the elderly. Live lactic acid bacteria (LAB) administered in food, such as probiotics, may be good antioxidant candidates. Nevertheless, information about LAB-induced oxidative stress protection is scarce. To identify and characterize new potential antioxidant probiotic strains, we have developed a new functional screening method using the nematode Caenorhabdit…
Cloning of Rac and Rho-GDI from tobacco using an heterologous two-hybrid screen.
2000
International audience; To examine whether molecular similarities exist between the animal and plant Rho GTPase signaling pathways, we have developed a heterologous two-hybrid screening method. By this technique, we have cloned a cDNA encoding a tobacco Rac-like protein able to interact with a mammalian Rho-GDI. In a second screen this tobacco Rac was used as a bait and a tobacco homologue of Rho-GDI was identified. These results show that some components of the animal and plant Rac signaling pathways are similar enough to allow their interaction in an heterologous approach. Moreover these data suggest a similar regulation of Rho GTPases in animals and plants.
TRAIL in cancer therapy: present and future challenges.
2007
International audience; Since its identification in 1995, TNF-related apoptosis-inducing ligand (TRAIL) has sparked growing interest in oncology due to its reported ability to selectively trigger cancer cell death. In contrast to other members of the TNF superfamily, TRAIL administration in vivo is safe. The relative absence of toxic side effects of this naturally occurring cytokine, in addition to its antitumoural properties, has led to its preclinical evaluation. However, despite intensive investigations, little is known in regards to the mechanisms underlying TRAIL selectivity or efficiency. An appropriate understanding of its physiological relevance, and of the mechanisms controlling ca…
A role for the peroxisomal 3-ketoacyl-CoA thiolase B enzyme in the control of PPARα-mediated upregulation of SREBP-2 target genes in the liver.: ThB …
2011
International audience; Peroxisomal 3-ketoacyl-CoA thiolase B (Thb) catalyzes the final step in the peroxisomal β-oxidation of straight-chain acyl-CoAs and is under the transcription control of the nuclear hormone receptor PPARα. PPARα binds to and is activated by the synthetic compound Wy14,643 (Wy). Here, we show that the magnitude of Wy-mediated induction of peroxisomal β-oxidation of radiolabeled (1-(14)C) palmitate was significantly reduced in mice deficient for Thb. In contrast, mitochondrial β-oxidation was unaltered in Thb(-/-) mice. Given that Wy-treatment induced Acox1 and MFP-1/-2 activity at a similar level in both genotypes, we concluded that the thiolase step alone was respons…
NOTCH, a new signaling pathway implicated in holoprosencephaly.
2011
International audience; Genetics of Holoprosencephaly (HPE), a congenital malformation of the developing human forebrain, is due to multiple genetic defects. Most genes that have been implicated in HPE belong to the sonic hedgehog signaling pathway. Here we describe a new candidate gene isolated from array comparative genomic hybridization redundant 6qter deletions, DELTA Like 1 (DLL1), which is a ligand of NOTCH. We show that DLL1 is co-expressed in the developing chick forebrain with Fgf8. By treating chick embryos with a pharmacological inhibitor, we demonstrate that DLL1 interacts with FGF signaling pathway. Moreover, a mutation analysis of DLL1 in HPE patients revealed a three-nucleoti…
The Genome of the Sea Urchin Strongylocentrotus purpuratus
2006
We report the sequence and analysis of the 814-megabase genome of the sea urchin Strongylocentrotus purpuratus , a model for developmental and systems biology. The sequencing strategy combined whole-genome shotgun and bacterial artificial chromosome (BAC) sequences. This use of BAC clones, aided by a pooling strategy, overcame difficulties associated with high heterozygosity of the genome. The genome encodes about 23,300 genes, including many previously thought to be vertebrate innovations or known only outside the deuterostomes. This echinoderm genome provides an evolutionary outgroup for the chordates and yields insights into the evolution of deuterostomes.
Food Intake Adaptation to Dietary Fat Involves PSA-Dependent Rewiring of the Arcuate Melanocortin System in Mice
2012
International audience; Hormones such as leptin and ghrelin can rapidly rewire hypothalamic feeding circuits when injected into rodent brains. These experimental manipulations suggest that the hypothalamus might reorganize continually in adulthood to integrate the metabolic status of the whole body. In this study, we examined whether hypothalamic plasticity occurs in naive animals according to their nutritional conditions. For this purpose, we fed mice with a short-term high-fat diet (HFD) and assessed brain remodeling through its molecular and functional signature. We found that HFD for 3 d rewired the hypothalamic arcuate nucleus, increasing the anorexigenic tone due to activated pro-opio…