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

We examined the effect of medroxyprogesterone acetate (MPA) on secondary spreading of endometrial cancer. There was no significant difference in the adhering capacity of dispersed Ishikawa cells (derived from well-differentiated endometrial cancer) to a cell basement membrane matrix, fibronectin or laminin between cells treated with MPA, with cortisol, and without treatment. The adhering capacity of cells treated with cortisol to collagen type IV was higher than that without treatment. However, the adhering capacity was little affected by treatment with MPA. These results indicate that although cortisol may induce the initial process of metastasis by inducing the attachment of tumor cells to the basement membrane of vascular endothelium, MPA has no influence on the attachment, although it has a glucocorticoid action similar to that of cortisol. There was no significant difference in tumor angiogenesis factor (TAF) or fibroblast growth factor (FGF) activity of the tumor extract from Ishikawa cell colonies between cortisol-treated and control group. TAF or FGF activity of the MPA-treated group was lower than that of the control group. MPA may reduce the neovascularization in the terminal process of metastasis via the reduction of TAF and FGF produced by tumor cells, in spite of its glucocorticoid action.
 ...
PMID:Effect of medroxyprogesterone acetate on secondary spreading of endometrial cancer. 252 39

The human multipotential hematopoietic cell line K562 expresses fibronectin receptor (FNR) subunits of 160 kDa (alpha chain) and 120 kDa (beta chain). Treatment with 12-O-tetradecanoylphorbol 13-acetate (TPA) led to reduced binding of K562 to immobilized fibronectin (FN), although treated cells expressed 10-fold more cell surface FNR than untreated cells. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis confirmed this and showed altered electrophoretic mobilities of FNR subunits from TPA-treated cells. TPA treatment affected N-linked glycosylation, as tunicamycin treatment of K562 cells abolished differences in FNR mobility. Sialidase treatment of FNR immunoprecipitates minimized and sialidase treatment of intact cells eliminated these mobility differences between subunits from control and TPA-treated cells. Reduced sialylation of FNR from TPA-treated cells was further demonstrated by chromatography with bead-coupled lectins and by the greater negative charge of untreated K562 FNR subunits in two-dimensional isoelectric focusing-polyacrylamide gel electrophoresis. A relationship between reduced FNR sialylation and reduced FN binding was suggested by adhesion assays of sialidase-treated K562 which showed that desialylation of cell surface FNR was associated with decreased cell adhesion. Thus, TPA treatment reduces the function, increases the expression, and alters the structure of K562 FNR, and these changes appear to involve FNR sialylation.
 ...
PMID:Phorbol ester induces increased expression, altered glycosylation, and reduced adhesion of K562 erythroleukemia cell fibronectin receptors. 252 13

The role that the intracellular mediators, cAMP and Ca2+/phosphatidylserine-dependent protein kinase C, play in the regulation of endothelial cell (EC) motility was investigated. The adenylate cyclase activator, forskolin, at 10 microM induced rapid and reversible alterations in the shape of cultured human EC, disappearance of actin bundles and the concentration of F-actin at cell borders. Actin reorganization provoked by forskolin coincide with redistribution of vinculin to the cell periphery and rapid elimination of surface-associated fibronectin. A protein kinase C activator, phorbol 12-myristate 13-acetate (PMA) at 10-100 microM induced no visible alterations of cell shape, but enhanced the effect of forskolin. PMA stimulated formation of "stress fibers" and increased the number of vinculin plaques in central areas of the cell. A decrease in the amount of the surface-associated fibronectin in PMA-treated cells has also been observed, but, this effect was considerably slower than that produced by forskolin. Forskolin, but not PMA stimulated phosphorylation of the major intermediate filament protein, vimentin.
 ...
PMID:Effects of forskolin and phorbol-myristate-acetate on cytoskeleton, extracellular matrix and protein phosphorylation in human endothelial cells. 254 28

The purposes of this study were (1) to investigate the chronology of events in cellular and biochemical changes thought to be important in the development of silicosis, (2) to relate these to changes in lung function and radiograph, and (3) to evaluate the relation of quartz exposure and retention to individual response leading to early silicosis. Thirty-six sheep were exposed by repeated intratracheal infusion at 10-day intervals to 100 mg Minusil-5 in 100 ml saline (Si group), and 10 sheep were exposed at the same intervals to 100 ml saline (control). All sheep were investigated at 3-month intervals by chest radiograph, lung function, and lung lavage. At month 9, chest radiograph score of parenchymal opacities was significantly increased at 2.8 +/- 0.6 versus 0.4 +/- 0.4 in the Si group (p less than .05), establishing early radiologic silicosis. Lung function was significantly altered with reduction in lung compliance, vital capacity, and diffusion capacity (p less than .05). Lung lavage cellularity revealed significant increase in total cells (X 2.5), macrophages (X3), and neutrophils (X3). Albumin in BAL remained at the control level. Fibronectin production was significantly increased, as was the fibroblast growth activity, without significant change in procollagen 3 at this early stage of disease. Total phospholipids were significantly elevated in the Si-exposed sheep, and the profile demonstrated an increase in all the phospholipid components. Spontaneous release of hydrogen peroxide by alveolar cells was not increased, but in the presence of phorbol myristate acetate (PMA) higher levels of peroxide were found in the quartz-exposed sheep (p less than .05). The cellular and biochemical alterations of lung lavage preceded other changes. At month 12, there were good correlations (r greater than .49, p less than .001) between parameters evaluating related phenomena but poor correlations between measurements evaluating different aspects of the disorder. To investigate the heterogeneity in the individual response of sheep to the same exposure (susceptibility), individual quartz retention levels at month 12 were measured and found to correlate well with individual parameters of disease activity. We concluded that in early silicosis of sheep, cellular and biochemical changes in lung lavage preceded derangements of pulmonary function and radiographic abnormalities. Thereafter, parameters of lung lavage, lung function, and radiograph were significantly interrelated, but for a given exposure the degree of quartz retention appeared to determine the intensity of the silicotic process.
 ...
PMID:Quartz exposure, retention, and early silicosis in sheep. 254 36

It has been shown that H2O2, the dismutation product of O2., is produced at cell-surface interfaces. Nevertheless, the relationships between the degree of attachment itself, type of surface, and O2. production are not clear. Superoxide production can be measured by the O2.-dependent reduction of nitroblue tetrazolium to an insoluble formazan. Superoxide dismutase (SOD) may be unable to scavenge O2. produced between alveolar macrophages (AM) and a surface. Desferal-Mn(IV) (Des-Mn), a low molecular weight mimic of SOD, is protective against paraquat toxicity in vivo, presumably because of specificity for O2-. Using that assumption, Des-Mn was used to measure O2. production that occurred during adherence of AM. AM suspensions were placed on fibronectin-coated glass coverslips or uncoated glass coverslips or non-stick tissue culture plates. Adherence to the surfaces varied with fibronectin greater than glass greater than non-stick and the percent formazan positive cells was 60, 24, and 4, respectively. With SOD present, the percentage of formazan positive cells were 40, 17, and 2; however, in the presence of Des-Mn the percent stained cells was 4, 4, and 0. When phorbol myristate acetate (PMA) was added during adherence, the percent of formazan positive cells was 82, 57, and 44, respectively. With PMA, Des-Mn was able to inhibit 88-100% of formazan staining whereas SOD inhibition decreased more markedly with increasing adherence. These results indicated that the degree of attachment correlated with both the degree of NBT reduction and the relative effectiveness of Des-Mn versus SOD to scavenge O2..
 ...
PMID:Adhering lung macrophages produce superoxide demonstrated with desferal-Mn(IV). 254 53

Pump-1 cDNA has recently been isolated by screening a human tumor cDNA library with a transin (rat stromelysin) probe under low-stringency hybridization conditions. The cDNA codes for a potential protein with significant sequence similarity to the metalloproteinases collagenase and stromelysin, but which lacks the hemopexin-like domain characteristic of these enzymes. Expression of pump-1 cDNA in cos cells using an expression vector leads to secretion of a protein of Mr 28,000 with latent, organomercurial-activatable proteinase activity. Cos cells transfected with a partial pump-1 cDNA in the vector pPROTA secrete a fusion protein between the IgG-binding domains of staphylococcal protein A and pump-1. The fusion protein binds to IgG-Sepharose, and the bound fusion protein undergoes apparent autocleavage in the presence of 4-aminophenylmercuric acetate with elution of active pump-1 species of Mr 21,000 and 19,000. Active pump-1 degrades casein, gelatins of types I, III, IV, and V, and fibronectin and can activate collagenase. Active pump-1 is inhibited by EDTA, 1,10-phenanthroline, and the tissue inhibitor of metalloproteinases. These results show that, despite the absence of a hemopexin-like domain, pump-1 is a latent secreted metalloproteinase. Postpartum rat uteri contain elevated levels of rat pump-1 mRNA. On the basis of this observation, its size, and its substrate specificity, we suggest that pump-1 might correspond to a previously described uterine metalloproteinase, matrix metalloproteinase 7.
 ...
PMID:Pump-1 cDNA codes for a protein with characteristics similar to those of classical collagenase family members. 255 50

Production of fibronectin (Fn) and prostaglandin E2 (PGE2) by human alveolar macrophages (AM) which were obtained by bronchoalveolar lavage was studied in vitro. AM obtained from patients with idiopathic interstitial pneumonia (IIP) produced much more Fn than those from normal volunteers but produced less amounts of PGE2. We also tested the effect of lipopolysaccharide (LPS), phorbol 12-myristate 13-acetate (PMA), zymosan and albumin-anti albumin complex (alb-anti alb) on production of Fn and PGE2 from AM. LPS, PMA and zymosan suppressed Fn production but stimulated PGE2 production by AM from patients with IIP but indomethacin reversed the suppressive effect of LPS, PMA and zymosan on Fn production. On the contrary, alb-anti alb stimulated Fn production by AM. Furthermore, exogenous PGE2 suppressed Fn production by AM from patients with IIP in a dose-dependent manner. These data suggest that Fn production by AM may be changed by different stimuli or different states of disease, and there is close relationship between the production of Fn and PGE2 by AM.
 ...
PMID:[Production of fibronectin and PGE2 by cultured human alveolar macrophages]. 262 10

Okadaic acid is a non-phorbol 12-myristate 13-acetate (PMA)-type tumor promoter on mouse skin and known to be a potent inhibitor of serine/threonine protein phosphatases. Contrary to expectation from its tumor-promoting activity, okadaic acid was shown to have a potential to revert the phenotypes of cells transformed by raf and ret-II to that of normal cells. Two to 3 days after addition of 8 ng of okadaic acid per ml to the culture medium, raf and ret-II transformants changed to flat cells and gained contact inhibition. The amount of fibronectin, which was decreased in malignant transformed cells, was increased in the flat revertants. Moreover, okadaic acid caused a dose-dependent loss of ability to grow in soft agar. The morphology of the cells reverted to malignant phenotype within 1 week after removal of okadaic acid. The levels of mRNA and protein of activated c-raf in flat revertants were similar to those in parental transformed cells. The level of mRNA of ret-II was also not changed by flat reversion. No induction of flat reversion was observed with okadaic acid tetramethyl ether, an inactive compound, or a phorbol ester, PMA. As okadaic acid is a potent inhibitor of protein phosphatases 1 and 2A, the possibility that these phosphatases are involved in signal transduction from the raf and ret-II oncogenes is suggested.
 ...
PMID:Flat reversion by okadaic acid of raf and ret-II transformants. 269 80

The histological similarities and the common localization are the main causes of difficulties concerning the differential diagnosis between giant cell tumor of bone and chondroblastoma. The purpose of the present study was to detect whether histochemistry and/or immunohistochemistry could help to make the distinction between these two entities easier. The study was based on cases of chondroblastoma and giant cell tumor of bone from patients in the 2nd and 3rd decades of life. Histochemical detection of special intracellular and extracellular components (glycogen, glycosaminoglycans) as well as immunohistochemical investigation using various tumor markers (S-100, NSE, a-1-ACT, lysozyme, fibronectin) were performed on parallel paraffin sections. The presence of abundant intracytoplasmic glycogen granules and the immunoreactivity of the cells of chondroblastoma with S-100 and NSE, together with the presence of acidic sulfated glycosaminoglycans in the stroma, could help the differential diagnosis of this tumor from giant cell tumor of bone.
 ...
PMID:A combined immunohistochemical and histochemical approach on the differential diagnosis of giant cell epiphyseal neoplasms. 271 Jun 83

The effect of transforming growth factor type beta 1 (TGF-beta 1) on mononuclear phagocytes (macrophages), cells which play an important role in the inflammatory response resulting from tissue wounding, was investigated. We found that fibronectin production by murine inflammatory macrophages is significantly enhanced by highly purified human TGF-beta 1 in a time- and dose-dependent manner. Specifically, 2 pM TGF-beta 1 was sufficient to cause significant elevation of fibronectin levels, which peaked between 24 and 48 hr of incubation. Both TGF-beta 1-induced and basal levels of fibronectin were completely abolished by cycloheximide, suggesting that protein synthesis was required. Furthermore, fibronectin mRNA levels were significantly enhanced in TGF-beta 1-treated macrophages. The inductive capacity of TGF-beta 1 appeared specific since other agents such as phorbol myristate acetate and endotoxin failed to induce fibronectin production. Since macrophages have been recently shown to secrete an inactive form of TGF-beta 1, the ability of this precursor molecule to induce fibronectin production was tested. It was found that partially purified human platelet latent TGF-beta 1 could not induce fibronectin synthesis, whereas acid treatment of the same preparation which releases mature TGF-beta 1 enhanced fibronectin production. Taken together, results presented here suggest that inflammatory macrophages can directly contribute to the formation of extracellular matrix upon interaction with TGF-beta 1 and that these cells lack the ability to augment fibronectin production in response to a platelet-derived latent form of TGF-beta 1.
 ...
PMID:Effect of platelet-derived transforming growth factor (TGF) type beta 1 on murine inflammatory mononuclear phagocytes: increased fibronectin production. 273 28


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>