Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.2.1.23 (beta-galactosidase)
 14,648 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The 67-kDa protein identical to the enzymatically inactive spliced variant of beta-galactosidase is a major component of the non-integrin cell surface receptor expressed on fibroblasts, smooth muscle cells, chondroblasts, leukocytes, and certain cancer cell types. It recognizes several non-identical hydrophobic domains on elastin, laminin, and type IV collagen, provided they form a similar secondary conformation. The 67-kDa protein is not a transmembrane molecule, but immobilizes on the cell surface by an association with two other proteins, the 61-kDa neuraminidase and the 55-kDa 'protective protein'. The 67-kDa protein binds to matrix ligands in a calcium independent manner and only in the absence of galactosugars. Binding of these carbohydrate-bearing moieties causes such conformational changes of the 67-kDa protein that it loses the ability to bind its principal matrix ligands and separates from the cell surface. Galactosugars which inactivate this unique cell surface receptor may therefore modulate cell-matrix interactions, especially in such processes as SMC migration during vascular thickening, tumor cell metastasis, or tissue infiltration by the leukocytes. In elastin-producing cells, the 67-kDa protein associates with tropoelastin and serves as a molecular chaperone which facilitates its intracellular transport and extracellular assembly.
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PMID:Biological roles of the non-integrin elastin/laminin receptor. 892 81

-The increased delivery of serotonin (5-hydroxytryptamine, 5-HT) to the lung aggravates the development of hypoxia-induced pulmonary hypertension in rats, possibly through stimulation of the proliferation of pulmonary artery smooth muscle cells (PA-SMCs). In cultured rat PA-SMCs, 5-HT (10(-8) to 10(-6) mol/L) induced DNA synthesis and potentiated the mitogenic effect of platelet-derived growth factor-BB (10 ng/mL). This effect was dependent on the 5-HT transporter (5-HTT), since it was prevented by the 5-HTT inhibitors fluoxetine (10(-6) mol/L) and paroxetine (10(-7) mol/L), but it was unaltered by ketanserin (10(-6) mol/L), a 5-HT2A receptor antagonist. In PA-SMCs exposed to hypoxia, the levels of 5-HTT mRNA (measured by competitive reverse transcriptase-polymerase chain reaction) increased by 240% within 2 hours, followed by a 3-fold increase in the uptake of [3H]5-HT at 24 hours. Cotransfection of the cells with a construct of human 5-HTT promoter-luciferase gene reporter and of pCMV-beta-galactosidase gene allowed the demonstration that exposure of cells to hypoxia produced a 5.5-fold increase in luciferase activity, with no change in beta-galactosidase activity. The increased expression of 5-HTT in hypoxic cells was associated with a greater mitogenic response to 5-HT (10(-8) to 10(-6) mol/L) in the absence as well as in the presence of platelet-derived growth factor-BB. 5-HTT expression assessed by quantitative reverse transcriptase-polymerase chain reaction and in situ hybridization in the lungs was found to predominate in the media of pulmonary artery, in which a marked increase was noted in rats that had been exposed to hypoxia for 15 days. These data show that in vitro and in vivo exposure to hypoxia induces, via a transcriptional mechanism, 5-HTT expression in PA-SMCs, and that this effect contributes to the stimulatory action of 5-HT on PA-SMC proliferation. In vivo expression of 5-HTT by PA-SMC may play a key role in serotonin-mediated pulmonary vascular remodeling.
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PMID:Induction of serotonin transporter by hypoxia in pulmonary vascular smooth muscle cells. Relationship with the mitogenic action of serotonin. 1002 7

Local gene transfer into the vascular wall offers a promising alternative to treat atherosclerosis-related diseases. Blood vessels are among the easiest targets for gene therapy because of percutaneous, catheter-based treatment methods. On the other hand, gene transfer to the artery wall can also be accomplished from adventitia either by ex vivo gene transfer and implantation of transfected cells or by direct in vivo gene transfer methods. In the future, as the pathological processes in arteries are better understood, several therapeutic genes could be combined and these "gene cocktails" are expected to produce enhanced therapeutic effects in vascular gene therapy. We have developed a new, efficient technique for performing ex vivo gene transfer to rabbit arterial wall using autologous SMC. The cells were harvested from rabbit ear artery, transfected in vitro with VSV-G pseudotyped lacZ retrovirus, and returned back to the adventitial surface of the carotid artery using a silicone collar or collagen sheet placed around the artery. The transduced SMCs implanted with a high efficiency and expressed beta-galactosidase marker gene at a very high level 7 days and 14 days after the operation. The level of lacZ expression decreased thereafter, but was still easily detectable for at least 6 months and was exclusively localized to the site of cell implantation inside the collar. Development of new vectors, such as baculovirus, for gene transfer will provide targeted, efficient, and safer methods for gene delivery. Plasmids and viruses coding for more than one protein, and bearing regulatory elements, would be useful for future gene therapy applications. Also, constructing second-generation viruses that contain fewer endogenous genes in their genome may reduce immunological reactions caused by the first-generation adenoviruses. In conditions where stable expression of therapeutic proteins is needed, it is necessary to develop better ex vivo and in vivo gene transfer strategies. Also, production of viruses that can efficiently transfect nondividing cells will be important for future applications of vascular gene therapy. However, current knowledge from vascular gene transfer experiments strongly suggests that vascular gene transfer is a promising new alternative for the treatment of cardiovascular diseases.
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PMID:Gene therapy methods in cardiovascular diseases. 1188 76