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41.
Peterson JA Sheibani N David G Garcia-Pardo A Peters DM 《The Journal of biological chemistry》2005,280(8):6915-6922
Co-signaling events between integrins and cell surface proteoglycans play a critical role in the organization of the cytoskeleton and adhesion forces of cells. These processes, which appear to be responsible for maintaining intraocular pressure in the human eye, involve a novel cooperative co-signaling pathway between alpha5beta1 and alpha4beta1 integrins and are independent of heparan sulfate proteoglycans. Human trabecular meshwork cells isolated from the eye were plated on type III 7-10 repeats of fibronectin (alpha5beta1 ligand) in the absence or presence of the heparin (Hep) II domain of fibronectin. In the absence of the Hep II domain, cells had a bipolar morphology with few focal adhesions and stress fibers. The addition of the Hep II domain increased cell spreading and the numbers of focal adhesions and stress fibers. Cell spreading and stress fiber formation were not mediated by heparan sulfate proteoglycans because treatment with chlorate, heparinase, or soluble heparin did not prevent Hep II domain-mediated cell spreading. Cell spreading and stress fiber formation were mediated by alpha4beta1 integrin because soluble anti-alpha4 integrin antibodies inhibited Hep II domain-mediated cell spreading and soluble vascular cell adhesion molecule-1 (alpha4beta1 ligand)-induced cell spreading. This is the first demonstration of the Hep II domain mediating cell spreading and stress fiber formation through alpha4beta1 integrin. This novel pathway demonstrates a cooperative, rather than antagonistic, role between alpha5beta1 and alpha4beta1 integrins and suggests that interactions between the Hep II domain and alpha4beta1 integrin could modulate the strength of cytoskeleton-mediated processes in the trabecular meshwork of the human eye. 相似文献
42.
Barros NM Nascimento FD Oliveira V Juliano MA Juliano L Loisel T Nader HB Boileau G Tersariol IL Carmona AK 《The international journal of biochemistry & cell biology》2008,40(12):2781-2792
The PHEX gene (phosphate-regulating gene with homologies to endopeptidase on the X chromosome) identified as a mutated gene in patients with X-linked hypophosphatemia (XLH), encodes a protein (PHEX) that shows striking homologies to members of the M13 family of zinc metallopeptidases. In the present work the interaction of glycosaminoglycans with PHEX has been investigated by affinity chromatography, circular dichroism, protein intrinsic fluorescence analysis, hydrolysis of FRET substrates flow cytometry and confocal microscopy. PHEX was eluted from a heparin-Sepharose chromatography column at 0.8 M NaCl showing a strong interaction with heparin. Circular dichroism spectra and intrinsic fluorescence analysis showed that PHEX is protected by glycosaminoglycans against thermal denaturation. Heparin, heparan sulfate and chondroitin sulfate inhibited PHEX catalytic activity, however among them, heparin presented the highest inhibitory activity (Ki = 2.5 ± 0.2 nM). Flow cytometry analysis showed that PHEX conjugated to Alexa Fluor 488 binds to the cell surface of CHO-K1, but did not bind to glycosaminoglycans defective cells CHO-745. Endogenous PHEX was detected at the cell surface of CHO-K1 colocalized with heparan sulfate proteoglycans, but was not found at the cell surface of glycosaminoglycans defective cells CHO-745. In permeabilized cells, PHEX was detected in endoplasmic reticulum of both cells. In addition, we observed that PHEX colocalizes with heparan sulfate at the cell surface of osteoblasts. This is the first report that the metallopeptidase PHEX is a heparin binding protein and that the interaction with GAGs modulates its enzymatic activity, protein stability and cellular trafficking. 相似文献
43.
Bcl-2 is the founding member of a family of proteins which influences cell survival in response to a variety of stimuli including those from growth factor receptors and integrins. However, how these activities are coordinated through bcl-2 requires further investigation. bcl-2 interacts with paxillin, potentially linking cell survival and cell adhesive pathways. Paxillin is an adapter protein implicated in growth factor and integrin-mediated signal transduction pathways. Previous work in this laboratory demonstrated that loss of bcl-2 affects cell adhesion and migration characteristics of renal epithelial cells, perhaps through disruption of its interaction with paxillin. Here studies were performed to determine the bcl-2 binding motif in paxillin. The amino-terminal portion of paxillin, specifically its LD4 motif, was found to associate with bcl-2. However, the amino-terminal portion of paxillin with the LD4 domain deleted did not associate with bcl-2. The corresponding LD motif in other paxillin family members, Hic-5 and leupaxin, did not associate with bcl-2. Mutations in paxillin's LD4 motif made to mimic Hic-5 and leupaxin LD4-like motifs (E(268) --> R or S(272) --> H) abolished its association with bcl-2. Incubation of embryonic kidneys with paxillin's LD4 motif disrupted ureteric bud branching and morphogenesis, while incubation with the comparable Hic-5 LD motif did not significantly affect morphogenesis. These data suggest that paxillin's association with bcl-2 plays a unique role during kidney development that other paxillin family members may not be able to fulfill. 相似文献
44.
Ana Jiménez 《植物学报(英文版)》2007,49(7):982-992
The effects of NaCl stress on the activity of anti-oxidant enzymes (superoxide dismutase, catalase (CAT), peroxidase (POD), ascorbate peroxidase (APX), monodehydroascorbate reductase, dehydroascorbate reductase (DHAR), and glutathione reductase (GR)), anti-oxidant molecules (ascorbate and glutathione), and parameters of oxidative stress (malondialdehyde (MDA), electrolyte leakage, and H2O2 concentrations) were investigated in Cakile maritima, a halophyte frequent along the Tunisian seashore. Seedlings were grown in the presence of salt (100, 200, and 400 mmol/L NaCl). Plants were harvested periodically over 20 days. Growth was maximal in the presence of 0-100 mmol/L NaCl. At 400 mmol/L NaCl, growth decreased significantly. The salt tolerance of C. maritima, at moderate salinities, was associated with the lowest values of the parameters indicative of oxidative stress, namely the highest activities of POD, CAT, APX, DHAR, and GR and high tissue content of ascorbate and glutathione. However, prolonged exposure to high salinity resulted in a decrease in anti-oxidant activities and high MDA content, electrolyte leakage, and H2O2 concentrations. These results suggest that anti-oxidant systems participate in the tolerance of C. maritima to moderate salinities. 相似文献
45.
Sarah Jamali Annick Salzmann Nader Perroud Magali Ponsole-Lenfant Jennifer Cillario Patrice Roll Nathalie Roeckel-Trevisiol Ariel Crespel Jorg Balzar Kurt Schlachter Ursula Gruber-Sedlmayr Ekaterina Pataraia Christoph Baumgartner Alexander Zimprich Fritz Zimprich Alain Malafosse Pierre Szepetowski 《PloS one》2010,5(9)
46.
Effect of adding nano‐titanium dioxide on the microstructure,mechanical properties and in vitro bioactivity of a freeze cast merwinite scaffold 下载免费PDF全文
Nader Nezafati Masoud Hafezi Ali Zamanian Mandana Naserirad 《Biotechnology progress》2015,31(2):550-556
In the present research, merwinite (M) scaffolds with and without nano‐titanium dioxide (titania) were synthesized by water‐based freeze casting method. Two different amounts (7.5 and 10 wt%) of n‐TiO2 were added to M scaffolds. They were sintered at temperature of 1573.15°K and at cooling rate of 4°K/min. The changes in physical and mechanical properties were investigated. The results showed that although M and M containing 7.5 wt% n‐TiO2 (MT7.5) scaffolds had approximately the same microstructures in terms of pore size and wall thickness, these factors were different for sample MT10. In overall, the porosity, volume and linear shrinkage were decreased by adding different weight ratios of n‐TiO2 into the M structure. According to the obtained mechanical results, the optimum mechanical performance was related to the sample MT7.5 (E = 51 MPa and σ = 2 MPa) with respect to the other samples, i.e.: M (E = 47 MPa and σ = 1.8 MPa) and MT10 (E = 32 MPa and σ = 1.4 MPa). The acellular in vitro bioactivity experiment confirmed apatite formation on the surfaces of all samples for various periods of soaking time. Based on cell study, the sample which possessed favorable mechanical behavior (MT7.5) supported attachment and proliferation of osteoblastic cells. These results revealed that the MT7.5 scaffold with improved mechanical and biological properties could have a potential to be used in bone substitute. © 2015 American Institute of Chemical Engineers Biotechnol. Prog., 31:550–556, 2015 相似文献
47.
Nader Rahimi Eric Tremblay Laura McAdam Anita Roberts Bruce Elliott 《In vitro cellular & developmental biology. Animal》1998,34(5):412-420
Summary We have developed an in vitro system to examine the influence of adipocytes, a major mammary stromal cell type, on the growth of a murine mammary carcinoma,
SP1. Previously, we have shown that 3T3-L1 adipocytes release a mitogenic factor, hepatocyte growth factor, which strongly
stimulates proliferation of SP1 cells. We now show that 3T3-L1 pre-adipocytes secrete active inhibitory molecules which inhibit
DNA synthesis in SP1 cells. In addition, latent inhibitory activity is present in conditioned media (CM) from both pre-adipocytes
and adipocytes, and is activated following acid treatment. CM also inhibited DNA synthesis in Mv1Lu wild type epithelial cells,
but not DR27 mutant epithelial cells which lack TGF-β type II receptor. Inhibitory activity of CMs was partially abrogated
by neutralizing anti-TGF-β1 and anti-TGF-β2 antibodies, and was removed following ultrafiltration through membranes of 10
000 Mr but not 30 000 Mr pore size. These results show that the inhibitory effect on DNA synthesis is mediated by TGF-β1-like and TGF-β2-like molecules.
In addition, acid-treated CM as well as purified TGF-β inhibited differentiation of pre-adipocytes. Untreated pre-adipocyte
CM, but not mature adipocyte CM, spontaneously inhibited adipocyte differentiation. Together, these findings indicate that
pre-adipocytes spontaneously activate their own secreted TGF-β, whereas mature adipocytes do not, and suggest that activation
of TGF-β has a potent negative regulatory effect on adipocyte differentiation and tumor growth. Thus, TGF-β may be an important
modulator of tumor growth and adipocyte differentiation via both paracrine and autocrine mechanisms. These findings emphasize
the importance of adipocyte-tumor interactions in the regulation of tumor microenvironment. 相似文献
48.
Nader Morshed William T Ralvenius Alexi Nott L Ashley Watson Felicia H Rodriguez Leyla A Akay Brian A Joughin PingChieh Pao Jay Penney Lauren LaRocque Diego Mastroeni LiHuei Tsai Forest M White 《Molecular systems biology》2020,16(12)
Alzheimer’s disease (AD) is characterized by the appearance of amyloid‐β plaques, neurofibrillary tangles, and inflammation in brain regions involved in memory. Using mass spectrometry, we have quantified the phosphoproteome of the CK‐p25, 5XFAD, and Tau P301S mouse models of neurodegeneration. We identified a shared response involving Siglec‐F which was upregulated on a subset of reactive microglia. The human paralog Siglec‐8 was also upregulated on microglia in AD. Siglec‐F and Siglec‐8 were upregulated following microglial activation with interferon gamma (IFNγ) in BV‐2 cell line and human stem cell‐derived microglia models. Siglec‐F overexpression activates an endocytic and pyroptotic inflammatory response in BV‐2 cells, dependent on its sialic acid substrates and immunoreceptor tyrosine‐based inhibition motif (ITIM) phosphorylation sites. Related human Siglecs induced a similar response in BV‐2 cells. Collectively, our results point to an important role for mouse Siglec‐F and human Siglec‐8 in regulating microglial activation during neurodegeneration. 相似文献
49.
Komal Sodhi Nitin Puri Gaia Favero Sarah Stevens Charles Meadows Nader G. Abraham Rita Rezzani Hayden Ansinelli Edward Lebovics Joseph I. Shapiro 《PloS one》2015,10(6)
Background
Oxidative stress underlies the etiopathogenesis of nonalcoholic fatty liver disease (NAFLD), obesity and cardiovascular disease (CVD). Heme Oxygenase-1 (HO-1) is a potent endogenous antioxidant gene that plays a key role in decreasing oxidative stress. Sirtuin1 (SIRT1) belongs to the family of NAD-dependent de-acyetylases and is modulated by cellular redox.Hypothesis
We hypothesize that fructose-induced obesity creates an inflammatory and oxidative environment conducive to the development of NAFLD and metabolic syndrome. The aim of this study is to determine whether HO-1 acts through SIRT1 to form a functional module within hepatocytes to attenuate steatohepatitis, hepatic fibrosis and cardiovascular dysfunction.Methods and Results
We examined the effect of fructose, on hepatocyte lipid accumulation and fibrosis in murine hepatocytes and in mice fed a high fructose diet in the presence and absence of CoPP, an inducer of HO-1, and SnMP, an inhibitor of HO activity. Fructose increased oxidative stress markers and decreased HO-1 and SIRT1 levels in hepatocytes (p<0.05). Further fructose supplementation increased FAS, PPARα, pAMPK and triglycerides levels; CoPP negated this increase. Concurrent treatment with CoPP and SIRT1 siRNA in hepatocytes increased FAS, PPARα, pAMPK and triglycerides levels suggesting that HO-1 is upstream of SIRT1 and suppression of SIRT1 attenuates the beneficial effects of HO-1. A high fructose diet increased insulin resistance, blood pressure, markers of oxidative stress and lipogenesis along with fibrotic markers in mice (p<0.05). Increased levels of HO-1 increased SIRT1 levels and ameliorated fructose-mediated lipid accumulation and fibrosis in liver along with decreasing vascular dysfunction (p<0.05 vs. fructose). These beneficial effects of CoPP were reversed by SnMP.Conclusion
Taken together, our study demonstrates, for the first time, that HO-1 induction attenuates fructose-induced hepatic lipid deposition, prevents the development of hepatic fibrosis and abates NAFLD-associated vascular dysfunction; effects that are mediated by activation of SIRT1 gene expression. 相似文献50.
Christian Dejaco Bastian Oppl Paul Monach David Cuthbertson Simon Carette Gary Hoffman Nader Khalidi Curry Koening Carol Langford Kathleen McKinnon-Maksimowicz Philip Seo Ulrich Specks Steven Ytterberg Peter A. Merkel Jochen Zwerina 《PloS one》2015,10(3)