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 ACE1 gene of the yeast Saccharomyces cerevisiae is required for copper-inducible transcription of the metallothionein gene (CUP1). The sequence of the cloned ACE1 gene predicted an open reading frame for translation of a 225-amino-acid polypeptide. This polypeptide was characterized by an amino-terminal half rich in cysteine residues and positively charged amino acids. The arrangement of many of the 12 cysteines in the configuration Cys-X-Cys or Cys-X-X-Cys suggested that the ACE1 protein may bind metal ions. The carboxyl-terminal half of the ACE1 protein was devoid of cysteines but was highly acidic in nature. The ability of a bifunctional ACE1-beta-galactosidase fusion protein to accumulate in yeast cell nuclei was consistent with the possibility that ACE1 plays a direct role in the regulation of copper-inducible transcription of the yeast metallothionein gene.
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PMID:A cysteine-rich nuclear protein activates yeast metallothionein gene transcription. 265 99

The AMT1 metalloregulatory trans-acting factor from Candida glabrata was found to functionally mimic the ACE1 metalloregulatory trans-acting factor from Saccharomyces cerevisiae in the copper-induced expression of the chromosomal S. cerevisiae metallothionein gene. Plasmid constructs with promoters of various metal-inducible genes fused to the bacterial beta-galactosidase (lacZ) reporter gene were used in S. cerevisiae to evaluate the roles of ACE1 and AMT1 in mediating metal-stimulated expression. Promoters from the S. cerevisiae CUP1 gene and Cu,Zn-superoxide dismutase (SOD1) and from the C. glabrata MT genes MTI, MTIIa, and MTIIb were used. The ACE1 factor was effective in the metalloregulation of the two S. cerevisiae promoters, CUP1 and SOD1, but of only one C. glabrata promoter, MTI. AMT1 was found to be effective in the metalloregulation of all three C. glabrata MT promoters and the two S. cerevisiae promoters tested. The regulation mediated by both ACE1 and AMT1 was copper-dependent and copper-specific. Episomally expressed SWI5, a distinct trans-acting factor of S. cerevisiae, enhanced only the basal expression from promoters. The SWI5 enhancement was not metal dependent. In conclusion, AMT1 and ACE1 are functionally homologous in metal-specific regulation, AMT1 appears to be more promiscuous than ACE1 in this function.
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PMID:Regulation of metallothionein genes by the ACE1 and AMT1 transcription factors. 850 91

It has been demonstrated that BMPs, IGFs, and TGFbetas improve the process of bone healing in vivo. We have suggested the use of gene therapy as a possible way to deliver growth factors to fracture sites in order to improve repair. The aim of this study was to develop a minimally invasive gene therapy approach to treat bone injuries locally without damaging the local blood circulation. A segmental defect of 1.3 cm was created in the diaphysis of the femur in mature NZW rabbits. Internal fixation with 7-hole DCP plates and 2.7 mm screws was used to stabilize the bone. After building a chamber by tightly closing the muscles around the segmental defect, 0.5 ml of either saline solution or a collagen gel containing 1 x 10(10) particles of adenovirus carrying cDNA encoding either the bacterial beta-galactosidase gene (LacZ), or the firefly luciferase gene were injected into the gap. The control side received 0.5 ml of saline solution without virus particles. Bone marrow, cortical and trabecular bone and surrounding muscle were harvested from the injected femur and were analyzed for local gene expression through X-gal staining or measurement of local luciferase activity. To determine whether distant sites were transduced, tissue from the spleen, liver, and lung were harvested as well as bone, bone marrow and muscle from the contralateral diaphysis of the femur. The delivery of the adenoviral vector suspended in saline solution led to local transduction of the bone, bone marrow and the muscle surrounding the gap. No luciferase activity was found in the contralateral femur, lung, or spleen, and only transient luciferase activity was seen in the liver. While marker gene expression persisted within the surrounding soft tissues for at least 2 weeks, the expression in bone lasted up to 6 weeks. This study has shown that it is possible to use adenoviral vectors to transfer and express genes locally within a segmental defect. Gene expression persisted for several weeks, which may be already sufficient to accelerate repair.
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PMID:A gene therapy approach to accelerating bone healing. Evaluation of gene expression in a New Zealand white rabbit model. 1040 58

Currently nanosystems composed of polynucleotides and lipid vesicles (nanolipoplexes) are considered to be promising tools for gene therapeutics. Successful in vivo application of these vectors depends on their physicochemical, technological and biological characteristics including morphology, size distribution, molecular interactions and stability. Anionic nanoliposomes (DPPC:DCP:CHOL) were prepared by two different techniques, namely the conventional thin-film hydration method followed by extrusion, and the heating method (HM), in which no volatile solvent or detergent is used. A non-viral and non-cationic gene transfer vector was constructed by incorporating plasmid DNA (pcDNA3.1/His B/lacZ) to the HM-nanoliposomes by the electrostatic mediation of Ca(2+) ions. Transfection efficiency of the nanolipoplexes was evaluated using a human bronchial epithelial cell line (16HBE14o-) in the presence of serum. Particle characterisation, stability of the formulations and lipid-DNA interaction studies were performed using transmission electron microscopy (TEM) and light scattering. TEM pictures of nanolipoplexes showed presence of two to four closely packed vesicles with signs of fusion. Efficient delivery of plasmid DNA and subsequent beta-galactosidase expression was achieved using the anionic nanolipoplexes. Transfection efficiency increased with lipid:DNA ratio up to 7:1 (w/w), where transfection efficiency was 12-fold higher than in untreated cells. Further increase in lipid ratio decreased transfection. These nanolipoplexes appear to be safe, stable and efficient in the protection and delivery of DNA to different cells and tissues.
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PMID:Prospects of anionic nanolipoplexes in nanotherapy: transmission electron microscopy and light scattering studies. 1768 72

The aim of this study is to investigate the chemical retinoic acid (RA) disruption at the level of retinoid X receptor (RXR) functioning. This assay makes use of recombined human RXR gene and reporter gene yeast, which specifically expresses beta-galactosidase when incubated with exogenous 9-cis retinoic acid (9-cis RA). Agonistic and antagonistic actions of chemicals including a series of phenols, phthalates, organochlorine pesticides (OCPs) were tested in the absence and presence of 5 x 10(-6)mol/L 9-cis RA, at which maximal beta-galactosidase activity could be induced. The results obtained reveal that some chemicals, e.g., 2-t-butylphenol, 2-isopropylphenol, 2,4-dichlorophenol (2,4-DCP), 3,4-dichlorophenol (3,4-DCP), 4-tert-octylphenol (4-t-OP) and hexachlorobenzene (HCB), are RXR agonists. Especially, bisphenol A (BPA) showed high induction activity to RXR when tested with metabolization. The 20% relative inhibitory concentration (RIC20) values of r-hexachlorocyclohexane (HCH), p,p'-dichlorodiphenyltrichloroethane (p,p'-DDT) and 2,4-DCP with metabolization were lower than 1 x 10(-6)mol/L. These results suggest that BPA, HCH, p,p'-DDT and 2,4-DCP are chemicals that pose a threat to hRXR functioning. Altogether the results of the present study show that the newly developed, yeast two-hybrid assay can be used as a valuable tool for identification and quantification of compounds active in disturbing retinoid homeostasis at the level of RXR.
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PMID:A two-hybrid yeast assay to quantify the effects of xenobiotics on retinoid X receptor-mediated gene expression. 1820 73