Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: HUMANGGP:009431 (fibronectin)
 32,104 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Incubation of the human promonocytic cell line U937 with 12-O-tetradecanoylphorbol-13-acetate (TPA) for 72 h resulted in differentiation into immature macrophage-like cells and was accompanied by marked morphological and functional changes. U937 cells which normally grow in suspension and show a smooth surface, extended pseudopodia and became adherent to each other and to the surface of the culture vessel. Concomitant with the TPA-induced adherence U937 cells ceased to proliferate. Our results show that phorbol ester-treated U937 cells exhibited markedly increased levels of fibronectin and of the cytoskeletal proteins actin, myosin and vimentin including a reorganization of actin and vimentin filaments. The induction of both cellular adherence and growth inhibition were accompanied by a significantly reduced level of cells expressing transferrin receptors and changes in cell surface antigen expression. Here, the expression of the leukocytefunction antigens (LFA-1), including CD11 and CD18 was markedly enhanced during phorbol ester-induced differentiation. TPA-treatment, however, failed to enhance the small amount of U937 cells expressing the monocyte/macrophage-specific CD14 antigen or expressing MHC class-II antigens. A detailed analysis of the CD14 cluster by 7 differential antibodies resulted in an induction of TM1, UCHM1, MEM15, My4, and 3C10, whereas the epitopes recognized by TM2 and Mo2 remained unaltered. Neither indomethacin nor interferon-gamma were capable of inducing a marked expression of these antigen epitopes in TPA-treated cells. Although these data demonstrate that during phorbol ester-induced differentiation U937 cells acquire many properties typically associated with macrophages, the failure to express marked levels of macrophage-specific cell surface antigens suggests a transition of U937 cells from a promonocytic to an immature macrophage intermediate state rather than into mature macrophage-like cells.
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PMID:TPA-induced differentiation and adhesion of U937 cells: changes in ultrastructure, cytoskeletal organization and expression of cell surface antigens. 274 2

The possible effects of a synthetic progesterone, medroxyprogesterone acetate (MPA), on carbon tetrachloride/phenobarbital (CCl4/PB)-induced rat liver injury were studied by morphological methods. CCl4/PB-treated rats showed extensive liver fibrosis consisting of procollagen type III aminoterminal propeptide-positive strands and fibres with concomitant extensive basement membrane deposits and fibronectin synthesis. MPA treatment after CCl4/PB-induced liver damage reduced alterations in cytoplasmic organelles, inflammation and hemorrhages and reversed the fibrosis, mostly around individual liver cells, possibly due to the normalization of cellular structure and function with a decrease in fibronectin deposits.
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PMID:Reversibility of rat liver cirrhosis by medroxyprogesterone acetate. 274 35

Eight mature horses with no prior signs of joint disease or history of intra-articular therapy were treated with 8 weekly intra-articular injections of methylprednisolone acetate. Treatments were given at a dose of 120 mg/joint into the right radiocarpal and intercarpal joints, with the left joints as untreated controls. Articular cartilage samples were obtained at necropsy 1, 4, and 8 weeks after the last injection. Compared with controls, cartilage from injected joints had a loss of hematoxylin basophilia and decreased intensity of staining in safranin O fast green dye. Chondrocyte necrosis and hypocellularity were observed in all samples of cartilage from treated joints. Proteoglycan content and its rate of synthesis were reduced. There was a progressive loss of proteoglycan content, whereas proteoglycan synthesis increased somewhat 4 and 8 weeks after treatment. Collagen content was unchanged, but its rate of synthesis was markedly inhibited. Collagen synthesis did not recover, but remained decreased at 5 to 15% of the values from untreated cartilage. Water percentage was increased, but fibronectin content was not significantly different. A single injection of methylprednisolone acetate was also given into the right metacarpophalangeal joints of 3 of the 8 horses in this group, with the left joints serving as untreated controls. Sixteen weeks after the treatment, cartilage of the treated joints had a loss of histochemical staining and proteoglycan content was reduced to 50% of control values. The mean rate of proteoglycan synthesis and mean fibronectin content were increased, but the differences were not statistically significant (P greater than 0.05). Other variables were essentially unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Changes in articular cartilage after intra-articular injections of methylprednisolone acetate in horses. 280 4

A neutral proteinase, capable of degrading gelatin, has been found in both an active and a latent form in the medium from the culture of rat mesangial cells. The latent form had an Mr of 80,000-100,000 and could be activated with either 4-aminophenylmercuric acetate or prolonged incubation at neutral pH. The active form of the enzyme was extensively purified. The estimated Mr of the purified enzyme on gel filtration was approximately 200,000, indicating that the active enzyme formed aggregates. However, analysis by SDS/polyacrylamide-gel electrophoresis under reducing conditions showed two protein bands, with Mr 68,000 and 66,000. Both proteins were found to contain proteolytic activity when run on SDS/substrate gels. The enzyme was inhibited by EDTA and 1,10-phenanthroline, but not by inhibitors for cysteine, serine or aspartic proteinases. The enzyme did not digest fibronectin, bovine serum albumin, proteoglycan or interstitial collagen. The enzyme degraded pepsin-solubilized placental type V collagen at 31 degrees C, whereas similarly solubilized type IV collagen was only degraded at higher temperatures. In addition, the neutral proteinase degraded native soluble type IV collagen. It also had activity on insoluble type IV collagen of glomerular basement membrane. The above properties suggest that the mesangial neutral proteinase belongs to the gelatinase group of metalloproteinases and that it may play a role in the normal turnover of extracellular glomerular matrix.
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PMID:The purification and characterization of a glomerular-basement-membrane-degrading neutral proteinase from rat mesangial cells. 284 Aug 92

Initiation of cell proliferation by thrombin requires signals generated by thrombin interaction with specific high-affinity receptors and thrombin enzymic activity. Using synthetic peptides representing various domains of thrombin, we have identified a region adjacent to the proteolytic pocket of thrombin which confers high-affinity binding and generation of mitogenic signals. One peptide, representing residues 508 to 530 of human prothrombin (p508-530), inhibits up to 70% of the specific binding of 125I-alpha-thrombin at concentrations of less than 100 nM, enhances the ability of thrombin to stimulate DNA synthesis and stimulates DNA synthesis in cells treated with 25 ng/ml phorbol myristate acetate (PMA). Thus, this peptide or a portion of this peptide appears to represent the high-affinity receptor binding domain of thrombin. In contrast to the 23 amino acid peptide (p508-530), the tetrapeptide RGDA (p517-520) contained in this region competes for 125I-thrombin binding at concentrations from 100 to 2000 nM, but inhibits rather than stimulates the mitogenic effects of alpha-thrombin. Non-homologous peptides, or fibronectin-specific peptides (such as RGDS or GRGDSP) do not compete for 125I-alpha-thrombin binding and have no effect on thrombin mitogenesis. These studies demonstrate that peptides representing portions of the binding domain of thrombin: i) can generate receptor-occupancy related signals that enhance thrombin mitogenesis and are themselves mitogenic in cells treated with PMA; or ii) in the case of RGDA (which may be too small to generate signals), can act as antagonists, inhibiting the mitogenic effects of thrombin by preventing thrombin-receptor interaction.
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PMID:Synthetic peptides bind to high-affinity thrombin receptors and modulate thrombin mitogenesis. 285 54

Methods to culture cells from papillomas induced by an initiation-promotion protocol in SENCAR mice were developed, and the resultant cell lines have been characterized. Using Eagle's medium with 0.05 mM Ca2+ conditioned by dermal fibroblasts and supplemented with 1 ng/ml epidermal growth factor (EGF) in culture dishes coated with collagen and fibronectin, six cell lines (PA, PB, PC, PD, PE and PF) were established from separate pools of papillomas. When tested for tumorigenicity in nude mice by injection of a cell suspension or implantation of cells growing on a plastic liner, two of the lines (PC and PF) produced no tumors at any passage. In contrast, cells of the lines PA and PE produced highly differentiated squamous cell carcinomas from the earliest passage tested. The results with PB and PD were variable on tumorigenicity testing with some passages positive and others negative. When tested for responsiveness to Ca2+ (greater than 0.1 mM) as a differentiation stimulus, all lines responded. In the higher Ca2+ medium there was a 50-95% decrease in colony-forming efficiency, a slight decrease in [3H]thymidine incorporation (except for PA) and an increase in the number of cornified cells (except for early passage PF). Epidermal transglutaminase activity, a marker for terminal differentiation, was increased in the presence of medium with Ca2+ greater than 0.1 mM. However, unlike normal cells, only a fraction of the cells from each of the papilloma-derived cell lines terminally differentiated in response to Ca2+ while the remaining cells continued to proliferate, although at a slower rate. Responsiveness to phorbol ester tumor promoters was also examined in papilloma cell lines. 12-O-Tetradecanoylphorbol-13-acetate (TPA) treatment increased colony forming efficiency, DNA synthesis and colony size in all lines in medium with either 0.05 mM Ca2+ or 1.2 mM Ca2+. TPA treatment also increased ornithine decarboxylase activity in all lines, even at the higher Ca2+ concentration, although normal keratinocytes respond only when grown in medium with low Ca2+. TPA treatment caused only a slight increase in the number of cornified cells and no increase in epidermal transglutaminase activity in papilloma cells while it causes 10-fold or greater increases in these differentiation markers in normal keratinocytes. Thus papilloma cells appear to differ from normal keratinocytes in their ability to maintain a proliferating population under conditions favoring terminal differentiation, their consistent proliferative response to phorbol esters under these same conditions, and their reduced sensitivity to phorbol ester-induced terminal differentiation.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Cultivation and characterization of cells derived from mouse skin papillomas induced by an initiation-promotion protocol. 287 47

In serum-supplemented medium, exposure to the tumor promoter 4 beta-phorbol 12 beta-myristate 13 alpha-acetate (PMA) increases the proportion of SH-SY5Y neuroblastoma cells with neurites and increases the average neurite length. In the present study, under serum-free conditions, PMA treatment had the opposite effects, i.e., retarded neurite sprouting and partially inhibited neurite elongation. This inhibition in neurite outgrowth was partially antagonized by the addition of serum fibronectin (FN) to the medium or substratum. In the absence of PMA, SH-SY5Y cells grown under serum-free conditions showed extensive neurite outgrowth as well as the capacity to secrete FN into their microenvironment and form FN-containing substratum-attachment sites. Immunogold labeling and whole mount transmission electron microscopy (WMTEM) demonstrated FN-containing contact pads at sites where filopodia attached to the substratum and focal plaques on the underside of growth cone margins. The appearance and abundance of FN-containing contact pads and focal plaques were increased by the addition of exogenous FN to defined medium. Focal plaques appeared in close association with microfilament bundles, and nearly always with bundles that projected into filopodia attached to the substratum by contact pads. A method for immunolabeling FN in the filopodial contact pads of living cultures provided more direct evidence that filopodia and contact pads have a major role in FN-mediated attachment and are central in determining growth cone shape and the rate and direction of advance. In support of this view, we show that PMA treatment retards neurite sprouting, alters growth cone morphology and motility, and eliminates the appearance of microfilament bundles, filopodia, and FN-containing substratum-attachment plaques.
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PMID:Growth cone advance mediated by fibronectin-associated filopodia is inhibited by a phorbol ester tumor promoter. 290 85

Normal human melanocytes were separated from keratinocytes and maintained in culture using KGM medium supplemented with 12-O-tetradecanoylphorbol acetate and cholera toxin. The melanocytes were examined for the production of extracellular matrix molecules including fibronectin, laminin, and thrombospondin and for the utilization of these molecules in adhesion and motility assays. Melanocytes produced significant amounts of fibronectin as indicated by biosynthetic labeling/immunoprecipitation and by enzyme-linked immunosorbent assay (ELISA). Fibronectin was expressed on the surface of these cells. Laminin was also produced by melanocytes and expressed on the cell surface. The amount of laminin produced was significantly less than the amount of fibronectin. In contrast, melanocytes did not produce measurable thrombospondin as indicated by biosynthetic labeling/immunoprecipitation. Only traces of thrombospondin were detected by ELISA and no surface fluorescence was observed. When examined in adhesion and motility assays, melanocytes were found to utilize fibronectin for both processes. Laminin also stimulated adhesion but it was much less effective than fibronectin. Thrombospondin did not stimulate either attachment and spreading or motility. The pattern of extracellular matrix molecule production and utilization by melanocytes is significantly different from that shown previously for human epidermal keratinocytes (J. Varani et al., 1988, J. Clin. Invest. 81, 1537). These differences may underlie the differences with which the two cell types interact with basement membranes in vivo.
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PMID:Production and utilization of extracellular matrix components by human melanocytes. 291 77

The tumor promoter 12-O-tetradecanoylphorbol 13-acetate (TPA) did not alter the binding and release kinetics of externally added 125I-labeled plasma fibronectin to human lung fibroblasts in culture. Cell layer-bound plasma fibronectin was found to be chased into the medium at the same rate in tumor-promoter-treated as in non-treated cells. Unlabeled fibronectin accumulated to a much higher degree in the medium when tumor promoter was present. We conclude that TPA does not interfere with the fibronectin receptor on substrate-attached fibroblasts, but may influence intracellular fibronectin before it is bound to the extracellular matrix.
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PMID:Influence of tumor promoter on binding and release of fibronectin added to human lung fibroblasts. 294 79

Little information is available on the interaction between lymphocytes and fibronectin (fn). To gain a better understanding on this issue we examined the adhesion of 12 lymphoid cell lines, each exhibiting different phenotypic characteristics, to fn-coated substratum. Of the cell lines tested, five that adhered to fn possessed B-cell characteristics, while neither the T-cell lines nor the pre-B-cell line adhered. The physiology and biochemistry of adhesion of a B-cell line, MOPC 315, were examined in detail. Our results indicated that (1) the adhesion was a specific and time-dependent process, (2) the adhesion was temperature-dependent and inhibited by metabolic inhibitors, such as KCN and 2-deoxyglucose, (3) the presence of cycloheximide and pretreatment of cells with trypsin inhibited adhesion, (4) a 140-kDa surface protein was immunoprecipitated by anti-fn receptor antibodies, (5) the presence of divalent cations was essential for adhesion, (6) the presence of colchicine had no effect on adhesion, while cytochalasin B partially inhibited adhesion, and (7) the treatment of cells by both phorbol 12-myristate 13-acetate and calcium ionophore A23187 enhanced adhesion. In this study, we have established the interaction between lymphoid cell lines and fn. Such an interaction might play an important role in the behavior of lymphocytes in tissues.
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PMID:Adhesion of lymphoid cell lines to fibronectin-coated substratum: biochemical and physiological characterization and the identification of a 140-kDa fibronectin receptor. 295 22


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