Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.2.1.23 (beta-galactosidase)
14,648 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We and others have previously shown that a 67-kD cell surface elastin/laminin-binding protein (EBP) is responsible for cell adhesion to elastin and laminin and for mediating the process of elastin fiber assembly, but the nature of this protein was unknown. In this report we provide evidence that a 67-kD catalytically inactive form of beta-galactosidase produced by alternative splicing demonstrates immunological and functional similarity and sequence homology to the 67-kD EBP, suggesting that the two might be the same. Antibody prepared to a synthetic peptide, N-Ac-GSPSAQDEASPL, corresponding to a frame-shift-generated sequence unique to the alternatively spliced form of human beta-galactosidase, also recognized sheep EBP both on Western blotting and in aortic tissue. Furthermore, this synthetic peptide (S-GAL) binds to elastin and laminin, but not to fibronectin, collagen I, or collagen III. Moreover, both tropoelastin and laminin which bind to S-GAL peptide affinity columns can be specifically eluted from them with an excess of free S-GAL peptides. In addition, sequence homology among this splice variant of human beta-galactosidase, sheep EBP, and NH2-terminal sequences of some elastases suggests that these proteins share a common ligand-binding motif that has not been previously recognized.
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PMID:The 67-kD elastin/laminin-binding protein is related to an enzymatically inactive, alternatively spliced form of beta-galactosidase. 838 99

The fibronectin (FN) gene is under complex regulatory control in vitro and in vivo. Sequences from the rat FN gene directed efficient expression of a lacZ reporter gene product, beta-galactosidase, in NIH/3T3 mouse fibroblasts. Stable transfectants were generated to facilitate studies of gene regulation by cell growth state. The expression of FN-lacZ constructs increased approximately twofold when cultures attained confluence, relative to total protein. The magnitude of this increase correlates well with that observed for FN mRNA levels and protein synthesis rate. Fragments containing 4.9, 0.9, or 0.3 kbp upstream of the transcription start site are equally responsive to cell density and/or cell contact. Deletion of a cAMP-responsive element enhanced the response, suggesting a negative role for this sequence motif and demonstrating that the FN gene is regulated by cell density at the transcriptional level. The effect of high cell density is apparently different from decreased growth rate, as incubation with low serum did not result in increased expression of the lacZ reporter. Finally, conditioned medium from dense cells did not enhance reporter gene expression in sparse cells, suggesting that the density signal is not transmitted via a soluble factor.
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PMID:Modulation of transcription of the rat fibronectin gene by cell density. 889 5

Fibronectins (FNs) are essential for the proper development of embryonic mesenchymal tissues. A lacZ reporter gene has been fused to 4.9 kbp of DNA from the rat FN gene 5' flanking region, and this construct has been microinjected into fertilized mouse embryos to investigate the cis elements needed for the temporal and spatial regulation of FN in vivo. Histochemical staining of embryos for beta-galactosidase activity demonstrated that four independent lines shared a specific pattern of lacZ expression, reflecting the activity of the fibronectin sequences contained within the transgene. Specifically, somites stained positively for lacZ, but expression was spatially and temporally non-uniform, with higher levels in more caudal somites after a total of ca. 13 somite pairs had formed. This rostral-caudal gradient of lacZ expression in somites of embryos beyond this stage resembled the distribution of endogenous FN mRNA, as detected by whole mount in situ hybridization. The transgene was not expressed in the developing heart where endogenous FN mRNA was detected. Unexpectedly, highly localized staining was observed within the neural tube beginning at ca. E10-10.5, and two of the lines exhibited additional areas of staining due to the individual integration sites. Thus, the 4.9 kbp FN fragment appears to recapitulate closely the complex pattern of FN expression observed during somitogenesis. A smaller fragment of 0.9 kbp also directed lacZ expression in caudal somites at E9.5, suggesting that these sequences are sufficient to establish the spatio-temporal pattern.
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PMID:Expression of the mouse fibronectin gene and fibronectin-lacZ transgenes during somitogenesis. 902 61

The best methods for transducing hematopoietic progenitor cells usually involve either direct co-cultivation with virus-producing cells or human stromal supportive cells. However, these methods cannot be safely or easily applied to clinical use. Therefore, we aimed at improving retrovirus-mediated gene transfer into hematopoietic progenitors derived from cord blood CD34+ cells using viral supernatant to levels achieved at least with direct co-cultivation and under conditions that are suitable for clinical applications. In a first set of experiments, CD34+ cells were infected with supernatant containing amphotropic retroviral particles carrying the nls-lacZ reporter gene and the effects of centrifugation, cell adhesion to fibronectin, and Polybrene on the transduction of both clonogenic progenitors (CFC) and long-term culture initiating cells (LTC-IC) were studied. Transduction efficiency was evaluated on the percentage and total number of progenitors expressing the beta-galactosidase activity. Results show that a 48-hr infection of CD34+ cells with viral supernatant combining centrifugation at 1000 x g for 3 hr followed by adhesion to fibronectin allows transduction levels for both CFC and LTC-IC to be reached that are as good as using direct co-cultivation. In a second set of experiments, CD34+ cells were infected using this optimized protocol with pseudotyped retroviral particles carrying the gibbon ape leukemia virus (GALV) envelope protein. Under these conditions, between 50 and 100% of CFC and LTC-IC were transduced. Thus, we have developed a protocol capable of highly transducing cord blood progenitors under conditions suitable for a therapeutical use.
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PMID:High-level gene transfer to cord blood progenitors using gibbon ape leukemia virus pseudotype retroviral vectors and an improved clinically applicable protocol. 947 82

The aim of this study was to investigate the role of carbohydrate moieties attached to IgA1 hinge region in IgA1 self-aggregation and adhesion to extracellular matrix (ECM) proteins previously reported in IgA nephropathy. Serum IgA1 samples isolated from healthy individuals were digested with neuraminidase (NA), NA + beta-galactosidase, and NA + beta-galactosidase + alpha-N-acetylgalactosaminidase to remove the carbohydrates from the hinge region and were named asialo, agalacto, and naked IgA1, respectively. First, polyacrylamide gel electrophoresis was performed under the native condition, and consequently, a broad band indicating IgA1 self-aggregation was clearly observed in asialo, agalacto, and naked IgA1, but not in native IgA1. However, the broad band disappeared in sodium dodecyl sulfate-polyacrylamide gel electrophoresis under the nonreducing condition. Second, it was shown that IgA1 adhesion activities to type IV collagen, fibronectin, and laminin were significantly higher in asialo, agalacto, and naked IgA1 than in native IgA1, using enzyme-linked immunosorbent assay (asialo, agalacto, and naked versus native: P < 0.01). In addition, agalacto IgA1 had the highest affinity for all of the ECM proteins among the deglycosylated IgA1 (agalacto versus asialo and naked, P < 0.05). These results indicated that the removal of carbohydrates from the IgA1 molecule resulted in noncovalent self-aggregation and a significant increase in adhesion to the ECM proteins. It was therefore suggested that the IgA1 glycans played a protective role against aggregation and adhesion and that the underglycosylation of the IgA1 molecule found in IgA nephropathy could be involved in the nonimmunologic glomerular accumulation of IgA1.
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PMID:Protective role of IgA1 glycans against IgA1 self-aggregation and adhesion to extracellular matrix proteins. 980 90

Eyelid fusion normally occurs between E15.5 and E16.5 of mouse embryonic development and results from the migration of a population of periderm-derived epithelial cells over the corneal surface. Cell migration is known to depend on extracellular matrix receptors of the integrin family and to be regulated by growth factors. We were therefore interested that a failure of eyelid fusion has been reported in mice that are homozygous null for the transforming growth factor alpha (TGF-alpha) gene and in mice (invalpha5beta1) in which a transgenic alpha5beta1 integrin under the control of the involucrin promoter is misexpressed in differentiating keratinocytes. We examined expression of the alpha2beta1, alpha3beta1, alpha5beta1 and alpha6beta4 integrins during eyelid fusion in wild-type embryos and found selective upregulation of the alpha5beta1 integrin and its ligand, fibronectin, in the migrating eyelid tip cells. In TGF-alpha null embryos, the failure of eyelid fusion was correlated with a failure to upregulate the alpha5beta1 integrin and fibronectin in the tip cells. Using beta-galactosidase as a reporter gene in transgenic mice, we observed specific activity of the involucrin promoter in the eyelid tip cells. In invalpha5beta1 mice the transgenic human integrin was overexpressed not only in the tip cells but throughout the eyelid epidermis. In contrast, the endogenous, murine, alpha5beta1 integrin was only weakly expressed in the tip cells. We speculate that selective and coordinated expression of the alpha5beta1 integrin and fibronectin in eyelid tip cells is required for eyelid fusion and may be under the control of growth factors that include TGF-alpha.
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PMID:Role of integrins in mouse eyelid development: studies in normal embryos and embryos in which there is a failure of eyelid fusion. 985 78

In previous studies, RGD-CAP (collagen-associated protein containing the RGD sequence) isolated from a collagen fiber-rich fraction of pig cartilage was found to be orthologous to human (beta)ig-h3, which is synthesized by lung adenocarcinoma cells in response to transforming growth factor-beta. In the present study, we examined the effect of recombinant chick RGD-CAP on the spreading of chondrocytes and fibroblasts using RGD-CAP-coated dishes. When rabbit articular chondrocytes, chick embryonic sternal chondrocytes, rabbit peritoneal fibroblasts or human MRC5 fibroblasts were seeded on plastic dishes coated with RGD-CAP, cell spreading was enhanced compared with that on control dishes (bovine serum albumin- or beta-galactosidase-coated dishes). The effect of RGD-CAP on the cell spreading required divalent cations (Mg(2+) or Mn(2+)), and was reduced by EDTA. Monoclonal antibodies (mAbs) to the human integrin alpha(1) or beta(1) subunit, but not to the alpha(2), alpha(3), alpha(5) or beta(2) subunits, suppressed the RGD-CAP-induced spreading of human MRC5 fibroblasts. In a parallel experiment, the mAb to the alpha(5) subunit, but not the mAb to the alpha(1) subunit, suppressed fibronectin-induced spreading of these cells. These findings suggest that RGD-CAP is a novel ligand for integrin alpha(1)beta(1) that dose not bind to the RGD motif. Accordingly, an RGD-CAP fragment, which carries a deletion in the C-terminal region containing the RGD motif, was still capable of stimulating cell spreading.
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PMID:RGD-CAP ((beta)ig-h3) enhances the spreading of chondrocytes and fibroblasts via integrin alpha(1)beta(1). 1044 1

Increasing evidence indicates that tissue transglutaminase (tTG) plays a role in the assembly and remodeling of extracellular matrices and promotes cell adhesion. Using an inducible system we have previously shown that tTG associates with the extracellular matrix deposited by stably transfected 3T3 fibroblasts overexpressing the enzyme. We now show by confocal microscopy that tTG colocalizes with pericellular fibronectin in these cells, and by immunogold electron microscopy that the two proteins are found in clusters at the cell surface. Expression vectors encoding the full-length tTG or a N-terminal truncated tTG lacking the proposed fibronectin-binding site (fused to the bacterial reporter enzyme beta-galactosidase) were generated to characterize the role of fibronectin in sequestration of tTG in the pericellular matrix. Enzyme-linked immunosorbent assay style procedures using extracts of transiently transfected COS-7 cells and immobilized fibronectin showed that the truncation abolished fibronectin binding. Similarly, the association of tTG with the pericellular matrix of cells in suspension or with the extracellular matrix deposited by cell monolayers was prevented by the truncation. These results demonstrate that tTG binds to the pericellular fibronectin coat of cells via its N-terminal beta-sandwich domain and that this interaction is crucial for cell surface association of tTG.
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PMID:Cell surface localization of tissue transglutaminase is dependent on a fibronectin-binding site in its N-terminal beta-sandwich domain. 1052 59

The precise spatial-temporal role that expression and activation of transforming growth factor (TGF)-beta plays in mammalian organ morphogenesis remains incompletely understood. Using replication deficient adenoviral vectors containing engineered TGF-beta1 cDNAs, we studied the spatial effects of locally over-expressing either latent or mutated, constitutively active TGF-beta1 protein during embryonic mouse lung branching morphogenesis in culture. Transfer of exogenous genes into lung epithelium was achieved by intra-tracheal micro-injection of recombinant adenovirus, while submerging lungs in virus resulted in gene transfer into the pleura and subjacent mesenchymal cells, as revealed by cytochemical staining for beta-galactosidase. Only lungs transfected with active, but not latent TGF-beta1 gene, showed elevated levels of active TGF-beta. Epithelial over-expression of active, but not latent TGF-beta1, via intra-tracheal micro-injection inhibited lung branching morphogenesis by 36 %. In contrast, lungs submerged with either active or latent TGF-beta1 recombinant virus did not demonstrate an inhibitory effect upon branching. Pulmonary gene regulation was assayed by competitive polymerase chain reaction coupled with reverse transcription. Direct respiratory tract micro-injection of adenovirus over-expressing active TGF-beta1 resulted in a dose-dependent inhibition of epithelial surfactant protein (SP)-C and SP-B mRNA levels by up to 76 % and 70 %, respectively, while in contrast, fibronectin and matrix Gla protein (MGP) mRNA levels remained stable. However, lungs that had been submerged in adenovirus expressing active TGF-beta1 demonstrated a concentration-dependent induction of both fibronectin and MGP mRNA levels up to 4.3- and 4.7-fold respectively in the presence of 1 x 10(11) pfu/ml active TGF-beta1 virus. On the other hand, lungs treated with adenovirus expressing latent TGF-beta1 either by micro-injection or submerging failed to demonstrate any regulatory effect either upon epithelial or mesenchymal gene expression. We conclude that adenovector-mediated over-expression of activated TGF-beta1 in specific spatial compartments results respectively in either inhibition of branching morphogenesis and epithelium-specific gene expression, or in induction of matrix gene expression without affecting morphogenesis or epithelium-specific gene expression, depending on the route of administration. Also, the lack of effect of latent TGF-beta1 over-expression strongly suggests that TGF-beta activation per se provides an important locus of fine regulation of the spatial effects of TGF-beta signaling during embryonic lung branching morphogenesis.
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PMID:Spatial-specific TGF-beta1 adenoviral expression determines morphogenetic phenotypes in embryonic mouse lung. 1056 44

5-Bromodeoxyuridine was found to induce flat and enlarged cell shape, characteristics of senescent cells, and senescence-associated beta-galactosidase in mammalian cells regardless of cell type or species. In immortal human cells, fibronectin, collagenase I, and p21(wafl/sdi-1) mRNAs were immediately and very strongly induced, and the mortality marker mortalin changed to the mortal type from the immortal type. Human cell lines lacking functional p21(wafl/sdi-1), p16(ink4a), or p53 behaved similarly. The protein levels of p16(ink4a) and p53 did not change uniformly, while the level of p21(wafl/sdi-1) was increased by varying degrees in positive cell lines. Telomerase activity was suppressed in positive cell lines, but accelerated telomere shortening was not observed in tumor cell lines. These results suggest that 5-bromodeoxyuridine activates a common senescence pathway present in both mortal and immortal mammalian cells.
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PMID:5-Bromodeoxyuridine induces senescence-like phenomena in mammalian cells regardless of cell type or species. 1057 56


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