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1.
Denis Vivien Emmanuelle Petitfrre Laurent Martiny Herv Sartelet Philippe Galra Bernard Haye Jean-Pierre Pujol 《Journal of cellular physiology》1993,155(3):437-444
The knowledge of transforming growth factor (TGF)-β receptors has greatly progressed in the recent years. TGF-β receptors type I and II have been implicated in the modulation of cell proliferation, whereas type III (betaglycan) may act as a component presenting TGF-β to its signaling receptors. In addition, four other proteins that bind TGF-β1 or TGF-β2 have been recently identified in some cell lines, three being anchored to the membrane through a glycosylphosphatidylinositol (GPI). Despite this knowledge, the molecular mechanism of signal transduction through the TGF-β receptors remain an enigma. TGF-β family does not signal via any of the classical pathways. As GPI anchors of membrane proteins have been implicated in the transduction of some hormonal effects, we investigated the putative role of GPI in signaling the TGF-β effects on the proliferation of rabbit articular chondrocytes (RAC). We previously showed that TGF-β1 increased DNA replication rate of RAC, with a recruitment of cells in G2/M followed by a subsequent mitosis wave. Here, we find that the factor causes specific GPI hydrolysis, with correlated increase of inositolphosphate glycan (IPG). This effect was specifically inhibited by antibodies that bind TGF-β1. Using [3H]-inositol labeling and Triton X-114 extraction, we demonstrate that a hydrophobic material from the membrane is cleaved by treatment of cell cultures with phosphatidylinositol specific phospholipase C (PI-PLC) or by exposure to TGF-β, supporting that a PI-anchored molecule gives rise to IPG by TGF-β-induced hydrolysis. The biological relevance of this hydrolysis was demonstrated by the enhancing effect of purified IPG on the DNA synthesis rate, which mimicked the TGF-β action. These results demonstrate that IPG could be an early messenger in the cellular signaling that mediates the effect of TGF-β on RAC growth. © 1993 Wiley-Liss, Inc. 相似文献
2.
Emmanuelle Petitfrere Herve Sartelet Denis Vivien Isabel Varela-Nieto Hassan Elbtaouri Laurent Martiny Bernard Haye 《Biochimie》1998,80(12):1063-1067
In porcine thyrocytes, TSH alone does not induce cell growth. Recently, it has been demonstrated that acute stimulation by TSH of porcine thyrocytes leads to release an inositolphosphate glycan (IPG) described as a putative second messenger for various growth factors in different cell types. IPG isolated from porcine thyrocytes induces proliferation of fibroblasts EGFR T17 and porcine thyrocytes. In porcine thyrocytes we have confirmed that cell growth requires the presence of both TSH and insulin. This effect is reproduced by 8-bromo cyclic AMP suggesting a mediation by intracellular cyclic AMP. Cooperative effects between 8-bromo cyclic AMP and IPG have also been evidenced and are in favour of a crosstalk between distinct signalling pathways. 相似文献
3.
Balancing Selection of a Frame-Shift Mutation in the MRC2 Gene Accounts for the Outbreak of the Crooked Tail Syndrome in Belgian Blue Cattle
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Corinne Fasquelle Arnaud Sartelet Wanbo Li Marc Dive Nico Tamma Charles Michaux Tom Druet Ivo J. Huijbers Clare M. Isacke Wouter Coppieters Michel Georges Carole Charlier 《PLoS genetics》2009,5(9)
We herein describe the positional identification of a 2-bp deletion in the open reading frame of the MRC2 receptor causing the recessive Crooked Tail Syndrome in cattle. The resulting frame-shift reveals a premature stop codon that causes nonsense-mediated decay of the mutant messenger RNA, and the virtual absence of functional Endo180 protein in affected animals. Cases exhibit skeletal anomalies thought to result from impaired extracellular matrix remodeling during ossification, and as of yet unexplained muscular symptoms. We demonstrate that carrier status is very significantly associated with desired characteristics in the general population, including enhanced muscular development, and that the resulting heterozygote advantage caused a selective sweep which explains the unexpectedly high frequency (25%) of carriers in the Belgian Blue Cattle Breed. 相似文献
4.
Arnaud Sartelet Tobias Stauber Wouter Coppieters Carmen F. Ludwig Corinne Fasquelle Tom Druet Zhiyan Zhang Naima Ahariz Nadine Cambisano Thomas J. Jentsch Carole Charlier 《Disease models & mechanisms》2014,7(1):119-128
Chloride-proton exchange by the lysosomal anion transporter ClC-7/Ostm1 is of pivotal importance for the physiology of lysosomes and bone resorption. Mice lacking either ClC-7 or Ostm1 develop a lysosomal storage disease and mutations in either protein have been found to underlie osteopetrosis in mice and humans. Some human disease-causing CLCN7 mutations accelerate the usually slow voltage-dependent gating of ClC-7/Ostm1. However, it has remained unclear whether the fastened kinetics is indeed causative for the disease. Here we identified and characterized a new deleterious ClC-7 mutation in Belgian Blue cattle with a severe symptomatology including perinatal lethality and in most cases gingival hamartomas. By autozygosity mapping and genome-wide sequencing we found a handful of candidate variants, including a cluster of three private SNPs causing the substitution of a conserved tyrosine in the CBS2 domain of ClC-7 by glutamine. The case for ClC-7 was strengthened by subsequent examination of affected calves that revealed severe osteopetrosis. The Y750Q mutation largely preserved the lysosomal localization and assembly of ClC-7/Ostm1, but drastically accelerated its activation by membrane depolarization. These data provide first evidence that accelerated ClC-7/Ostm1 gating per se is deleterious, highlighting a physiological importance of the slow voltage-activation of ClC-7/Ostm1 in lysosomal function and bone resorption.KEY WORDS: CLCN7, Hamartomas, Osteopetrosis, Lysosomal storage, Ion homeostasis, Belgian Blue cattle 相似文献
5.
C. Masri G. Chagnon D. Favier H. Sartelet E. Girard 《Biomechanics and modeling in mechanobiology》2018,17(4):939-950
This work aims at observing the mechanical behavior of the membranous and spongy portions of urethrae sampled on male cadavers in compliance with French regulations on postmortem testing, in accordance with the Scientific Council of body donation center of Grenoble. In this perspective, a thermostatic water tank was designed to conduct ex vivo planar tension tests in a physiological environment, i.e., in a saline solution at a temperature of \(37 \pm 1\) \({^{\circ }}\hbox {C}\). In order to observe the anisotropy of the tissues, the samples were tested in two directions. Tests consisting of a series of load–unload cycles of increasing amplitudes were performed to highlight their viscous behavior. The results were then discussed according to the microstructure of tissue, which was investigated using different staining methods and histological analysis. The observed behaviors were then fitted using an anisotropic hyperelastic or a visco-hyperelastic matrix–fiber model. 相似文献
6.
Fanny Huyard Catherine Yzydorczyk Michele M. Castro Anik Cloutier Mariane Bertagnolli Hervé Sartelet Nathalie Germain Blandine Comte Richard Schulz Denis DeBlois Anne Monique Nuyt 《PloS one》2014,9(4)
Neonatal high-oxygen exposure leads to elevated blood pressure, microvascular rarefaction, vascular dysfunction and arterial (aorta) rigidity in adult rats. Whether structural changes are present in the matrix of aorta wall is unknown. Considering that elastin synthesis peaks in late fetal life in humans, and early postnatal life in rodents, we postulated that transient neonatal high-oxygen exposure can trigger premature vascular remodelling. Sprague Dawley rat pups were exposed from days 3 to 10 after birth to 80% oxygen (vs. room air control) and were studied at 4 weeks. Blood pressure and vasomotor response of the aorta to angiotensin II and to the acetylcholine analogue carbachol were not different between groups. Vascular superoxide anion production was similar between groups. There was no difference between groups in aortic cross sectional area, smooth muscle cell number or media/lumen ratio. In oxygen-exposed rats, aorta elastin/collagen content ratio was significantly decreased, the expression of elastinolytic cathepsin S was increased whereas collagenolytic cathepsin K was decreased. By immunofluorescence we observed an increase in MMP-2 and TIMP-1 staining in aortas of oxygen-exposed rats whereas TIMP-2 staining was reduced, indicating a shift in the balance towards degradation of the extra-cellular matrix and increased deposition of collagen. There was no significant difference in MMP-2 activity between groups as determined by gelatin zymography. Overall, these findings indicate that transient neonatal high oxygen exposure leads to vascular wall alterations (decreased elastin/collagen ratio and a shift in the balance towards increased deposition of collagen) which are associated with increased rigidity. Importantly, these changes are present prior to the elevation of blood pressure and vascular dysfunction in this model, and may therefore be contributory. 相似文献
7.
Geraldine Rath Christophe Schneider Benoit Langlois Hervé Sartelet Hamid Morjani Hassan E.L. Btaouri Stephane Dedieu Laurent Martiny 《The international journal of biochemistry & cell biology》2009,41(5):1165-1172
Doxorubicin and camptothecin are two cytotoxic chemotherapeutic agents triggering apoptosis in various cancer cells, including thyroid carcinoma cells. Recent studies revealed a critical role of ceramide in chemotherapy and suggested that anti-cancer drugs may kill tumor cells through sphingomyelinase activation. However, in comparison to sphingomyelin hydrolysis, the relative involvement of de novo ceramide synthesis remained poorly explored and highly controversial. Here, we evidenced that both doxorubicin and camptothecin triggered ceramide accumulation in thyroid carcinoma cells. We demonstrated that ceramide increase occurred via the de novo pathway without neither acidic nor neutral sphingomyelinase contribution. Interestingly, de novo ceramide generation was responsible for the drug-induced malignant cell apoptosis through a caspase-3-dependent pathway and a decrease of thrombospondin amount. Furthermore, blocking ceramide metabolism by inhibiting glucosylceramide synthase strengthened the camptothecin and doxorubicin-dependent effects. Altogether, we evidenced that de novo ceramide synthesis mediates the anti-tumor properties of doxorubicin and camptothecin in thyroid carcinoma and suggested that glucosylation of ceramide may contribute to the drug-resistance phenotype in thyroid malignancies. 相似文献
8.
Sid B Dedieu S Delorme N Sartelet H Rath GM Bellon G Martiny L 《The international journal of biochemistry & cell biology》2006,38(10):1729-1740
The low density lipoprotein receptor-related protein (LRP), a large scavenger receptor reported to mediate the uptake and degradation of various ligands, emerges as a promising receptor for targeting the invasive behaviour of human cancer cells. However, the accurate function of LRP during tumor invasion seems to be highly dependent on cellular context and remains controversial. The expression patterns of both this receptor and the main proteolytic systems involved in cell invasion were examined in two follicular thyroid carcinoma cell lines exhibiting different invasive phenotypes. We established that a low expression of LRP at the cell surface was associated to elevated extracellular MMP2 and urokinase plasminogen activator (uPA) activities as well as to high invasiveness properties. Surprisingly, neither exogenously added receptor-associated protein, an antagonist of LRP, nor LRP blocking antibodies significantly modified the amount of extracellular MMP2. Furthermore, the invasive phenotype of thyroid carcinoma cells was not related to their matrix metalloproteinases amount since different specific inhibitors of these proteases failed to affect the invasive properties of both cell lines. Additionally, blocking LRP-mediated clearance led to a further increase of the uPA amount and activities and to increased invasiveness in both cell lines. Finally thyroid carcinoma cells aggressiveness was widely increased by exogenous uPA; and anti-uPA antibodies treatments abolished both basal and receptor-associated protein-induced thyroid cell invasion. Overall our results identified the LRP-mediated clearance of uPA as one of the mechanisms involved during the control of human thyroid carcinoma cell invasion. 相似文献
9.
Rusciani A Duca L Sartelet H Chatron-Colliet A Bobichon H Ploton D Le Naour R Blaise S Martiny L Debelle L 《PloS one》2010,5(11):e14010
The sialidase activity of neuraminidase-1 (Neu-1) is responsible for ERK 1/2 pathway activation following binding of elastin peptide on the elastin receptor complex. In this work, we demonstrate that the receptor and lipid rafts colocalize at the plasma membrane. We also show that the disruption of these microdomains as well as their depletion in glycolipids blocks the receptor signaling. Following elastin peptide treatment, the cellular GM(3) level decreases while lactosylceramide (LacCer) content increases consistently with a GM(3)/LacCer conversion. The use of lactose or Neu-1 siRNA blocks this process suggesting that the elastin receptor complex is responsible for this lipid conversion. Flow cytometry analysis confirms this elastin peptide-driven LacCer generation. Further, the use of a monoclonal anti-GM(3) blocking antibody shows that GM(3) is required for signaling. In conclusion, our data strongly suggest that Neu-1-dependent GM(3)/LacCer conversion is the key event leading to signaling by the elastin receptor complex. As a consequence, we propose that LacCer is an early messenger for this receptor. 相似文献
10.
Jaisson S Sartelet H Perreau C Blanchevoye C Garnotel R Gillery P 《The FEBS journal》2008,275(12):3226-3235
Oxidative functions of polymorphonuclear neutrophils (PMNs), which play a deciding role in the phagocytosis process, are stimulated by extracellular matrix proteins such as type I collagen. Previous studies have demonstrated the involvement of a DGGRYY sequence located within the alpha(1) chain C-terminal telopeptide in type I collagen-induced PMN activation, but so far the mechanism has not been completely elucidated. We have recently demonstrated that collagen carbamylation (i.e. post-translational binding of cyanate to lysine epsilon-NH(2) groups) impairs PMN oxidative functions, suggesting the potential involvement of lysine residues in this process. The present study was devoted to the identification of lysine residues involved in the collagen-induced activation of PMNs. The inhibition of PMN activation by collagen in the presence of 6-amino-hexanoic acid, a structural analogue of lysine residues, confirmed the involvement of specific lysine residues. Modification of lysine residues by carbamylation demonstrated that only one residue, located within the alpha(1)CB6 collagen peptide, was involved in this mechanism. A recombinant alpha(1)CB6 peptide, designed for the substitution of lysine 1047 by glycine, exhibited decreased activity, demonstrating that the lysine residue at position 1047 within the collagen molecule played a significant role in the mechanism of activation. These results help to understand in more detail the collagen-mediated PMN activation mechanism and confirm the prominent involvement of lysine residues in interactions between extracellular matrix proteins and inflammatory cells. 相似文献