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:3.2.1.31 (beta-glucuronidase)
7,680 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mouse kidney beta-glucuronidase production is under multihormonal control. In normal mice, kidney glucuronidase is induced over 100-fold by testosterone. However, hypophysectomy reduces this induction to about 5% of normal. This loss in inducibility was in part restored by growth hormone. Simultaneous administration to hypophysectomized female mice of growth hormone and testosterone, but not of prolactin and testosterone, restored kidney glucuronidase concentration to half that found in testosterone-treated normal female mice. Growth hormone alone had no effect in hypophysectomized females nor did it enhance glucuronidase activity in testosterone-treated normal females. Radiolabeling experiments demonstrated that the enhancement by growth hormone of glucuronidase activity was accompanied by a corresponding increase in its rate of synthesis. Kidney hypertrophy and kidney glucuronidase production may be under common hormonal regulation. Testosterone or growth hormone treatment alone of hypophysectomized mice had little or no effect on either process, but combined treatment with the two hormones significantly enhanced both. The rate of synthesis of kidney glucuronidase is controlled by the Gur gene. Relative differences in kidney glucuronidase synthesis in mice of different Gur genotype were maintained in testosterone-treated hypophysectomized mice. This suggests that control of glucuronidase synthesis by the Gur locus is exerted by interaction with androgens rather than pituitary products.
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PMID:Roles of growth hormone and testosterone in the synthesis of mouse kidney glucuronidase. 72 3

Four groups of adult male hypophysectomized rats were injected subcutaneously twice daily between 0800-0900 hr and 1600-1700 hr with either saline diluent, 150 micrograms sheep prolactin and/or growth hormone (GH); intact rats received either saline or 150 micrograms bromocriptine twice daily. After 4 days of treatment, lysosomal enzyme assays revealed significant elevations in both acid phosphatase and alpha-mannosidase enzyme activities in the Harderian glands of saline-injected hypophysectomized rats compared to those in intact controls. beta-Glucuronidase levels were depressed and hexosaminidase activity unaffected by hypophysectomy treatment alone compared to intact controls. Lysosomal enzyme activities in hypophysectomized animals treated with prolactin were not different from the hypophysectomized control animals. However, treatment with GH alone or in combination with prolactin had a significant inhibitory effect on beta-glucuronidase, hexosaminidase, and alpha-mannosidase enzyme activities in the Harderian gland of hypophysectomized animals. Bromocriptine treatment in intact rats only elevated acid phosphatase activity. In summary, the patterns of responses did not reveal a role for prolactin in the control of Harderian gland lysosomal enzyme activities by the pituitary. However, some of the influence on this target system may be exerted by growth hormone.
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PMID:Lysosomal enzymes in the rat harderian gland are altered by either bromocriptine treatment or hypophysectomy and hormone replacement therapy. 296 92

The plant growth hormone indoleacetic acid (IAA) transcriptionally activates gene expression in plants. Some of the genes whose expression is induced by IAA encode a family of proteins in pea (PS-IAA4 and PS-IAA6) and Arabidopsis (IAA1 and IAA2) that contain putative nuclear localization signals that direct a beta-glucuronidase reporter protein into the nucleus. Pulse-chase and immunoprecipitation experiments have defined the t1/2 of the PS-IAA4 and PS-IAA6 proteins to be 8 and 6 min, respectively. Their most prominent feature is the presence of a beta alpha alpha motif similar to the beta-sheet DNA-binding domain found in prokaryotic repressors of the Arc family. Based on these data, we suggest that plant tissues express short-lived nuclear proteins as a primary response to IAA. We propose that these proteins act as activators or repressors of genes responsible for mediating the various auxin responses.
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PMID:Early auxin-induced genes encode short-lived nuclear proteins. 827 86

The effects of physiological and excessive levels of growth hormone (GH) on reproductive functions are poorly understood, and impairment of fertility is frequently observed in transgenic animals overexpressing GH genes. The present study was undertaken to determine the effects of chronic exposure to heterologous bovine GH (bGH) on the testes and accessory reproductive glands in transgenic mice. Endocrine function of the testes was evaluated by measuring the activities of two steroidogenic enzymes, delta 5-3 beta-hydroxysteroid dehydrogenase (delta 5-3 beta-HSD) and 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD). The activities of acid phosphatase, alkaline phosphatase and beta-glucuronidase, important hydrolytic enzymes of lysosomal origin, were measured in testes, seminal vesicles and ventral prostates in normal and transgenic mice. Testicular delta 5-3 beta-HSD activity was higher in transgenic than in normal mice, while testicular 17 beta-HSD activity in transgenic mice was not altered. Acid phosphatase activity was elevated in both seminal vesicles and ventral prostates of transgenic mice, while alkaline phosphatase activity was increased only in the prostate. The activity of beta-glucuronidase was elevated in the testes, seminal vesicles and ventral prostate gland of transgenic mice. These results suggest that chronic exposure to bGH is associated with significant stimulation of some hydrolytic enzymes in the testes and in the accessory reproductive glands of transgenic mice.
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PMID:Effects of the expression of bovine growth hormone on the testes and male accessory reproductive glands in transgenic mice. 839 Mar 24

The plant growth hormone auxin typified by indoleacetic acid (IAA) transcriptionally activates early genes in pea, PS-IAA4/5 and PS-IAA6, that are members of a multigene family encoding short-lived nuclear proteins. To gain first insight into the biological role of PS-IAA4/5 and PS-IAA6, promoter-beta-glucuronidase (GUS) gene fusions were constructed and their expression during early development of transgenic tobacco seedlings was examined. The comparative analysis reveals spatial and temporal expression patterns of both genes that correlate with cells, tissues, and developmental processes known to be affected by auxin. GUS activity in seedlings of both transgenic lines is located in the root meristem, sites of lateral root initiation and in hypocotyls undergoing rapid elongation. In addition, mutually exclusive cell-specific expression is evident. For instance, PS-IAA4/5-GUS but not PS-IAA6-GUS is expressed in root vascular tissue and in guard cells, whereas only PS-IAA6-GUS activity is detectable in glandular trichomes and redistributes to the elongating side of the hypocotyl upon gravitropic stimulation. Expression of PS-IAA4/5 and PS-IAA6 in elongating, dividing, and differentiating cell types indicates multiple functions during development. The common and yet distinct activity patterns of both genes suggest a combinatorial code of spatio-temporal co-expression of the various PS-IAA4/5-like gene family members in plant development that may mediate cell-specific responses to auxin.
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PMID:Differential activation of the primary auxin response genes, PS-IAA4/5 and PS-IAA6, during early plant development. 865 11

Current human gene therapy relies on genetic modification of the patient's own cells. An alternate non-autologous approach is to use universal cell lines engineered to secrete therapeutic products. Protection with immuno-isolation devices would allow the same recombinant cell line to be used for different patients, thus potentially lowering the cost of treatment. The feasibility of this idea has now been demonstrated in vitro and in vivo. Recombinant gene products with potential therapeutic applications (human growth hormone, factor IX, lysosomal enzymes, adenosine deaminase) have been expressed from genetically modified cells after encapsulation with alginate-poly-L-lysine-alginate or hydroxyethyl methacrylate-methyl methacrylate. We have also demonstrated the feasibility of this idea in vivo. After intraperitoneal implantation, genetically modified mouse Ltk- fibroblasts or C2C12 myoblasts encapsulated in alginate-poly-L-lysine-alginate could deliver recombinant gene products (human growth hormone, human factor IX) to the systemic circulation of mice. The clinical efficacy of this novel approach to gene therapy has now been shown in murine models of human diseases. In the Snell dwarf mice deficient in growth hormone production, implantation of encapsulated mouse myoblasts engineered to secrete mouse growth hormone resulted in increases in body weight, length and organ sizes, some to > 25% above those of the controls. In the Gus/Gus mice suffering from the lysosomal storage disease mucopolysaccharidosis type VII due to deficient beta-glucuronidase, implantation of encapsulated mouse fibroblasts engineered to secrete mouse beta-glucuronidase resulted in delivery of normal levels of the enzyme in the plasma and significant correction of the organ histopathology. Hence, delivery of recombinant gene products through bioartificial devices appears to be a promising strategy for the treatment of genetic diseases.
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PMID:Microcapsules as bio-organs for somatic gene therapy. 961 35

Microencapsulation of recombinant "universal" cells with immunoprotective membranes is an alternate approach to somatic gene therapy. Therapeutic gene products secreted by these cells can be delivered to different patients without immunosuppression or genetic modification of the host's cells. The encapsulation of different mammalian cell types (epithelial cells, fibroblasts, and myoblasts) is compared among three alginate-based microcapsules: (1) calcium-linked alginate microcapsules with a solubilized core and a poly-L-lysine-alginate-laminated surface; (2) barium-linked alginate beads with a gelled core; and (3) a hybrid formulation of barium-linked alginate beads with a poly-L-lysine-alginate-laminated surface. The mechanical stability of the different microcapsule types, as measured with a cone-and-plate shearing apparatus, was superior in the two barium-linked alginate beads. All cell types maintained high viability (65-90%) in culture after encapsulation. The recombinant gene products secreted by these cells (human growth hormone MW = 22,000, human factor IX MW = 57,000, and murine beta-glucuronidase MW = 300,000) were able to traverse the three microcapsule types at similar rates. Cell numbers within the microcapsules increased twofold to > 20-fold over 4 weeks, depending on the cell type. Epithelial and myoblast cell numbers were not affected by microcapsule formulation; however, fibroblasts proliferated the most in the calcium-linked alginate spheres. These results show that for culturing fibroblasts in a mechanically stable environment the classical calcium-linked microcapsules are adequate. However, where mechanical stability is a more critical requirement, the solid barium-linked gelled beads are more appropriate choices.
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PMID:Encapsulation of various recombinant mammalian cell types in different alginate microcapsules. 982 83

Arabidopsis thaliana expresses four nitrilases, three of which (NIT1, NIT2 and NIT3) are able to convert indole-3-acetonitrile to indole-3-acetic acid (IAA), the plant growth hormone, while the isozyme NIT4 is a beta-cyano-l-alanine hydratase/nitrilase. NIT3 promoter activity is marginal in leaves or roots of vegetative plants and undetectable in bolting and flowering plants, but its level increases strongly when plants experience sulphur deprivation. No other nitrilase genes respond to sulphur supply/deficiency. Neither N- nor P-deprivation cause detectable changes in NIT3 promoter activity. In transgenic plants expressing uidA under the control of the NIT3 promoter (NIT3p::uidA), sulphate deprivation leads to the appearance of beta-glucuronidase activity in shoots and particularly in roots, most strongly in the conductive tissues and lateral root primordia. Deletion analysis allowed localization of the sulphur-responsive element to a 317 bp segment of the NIT3 promoter encompassing nt -2151 to -1834 upstream of the transcriptional start point. Both nitrilase polypeptide and nitrilase activity were also induced by sulphur starvation. NIT3 promoter activity was strongly induced by O-acetylserine, suggesting that, as is the case with enzymes of sulphate assimilation, sulphate deficiency may be communicated to NIT3 via an increase in the level of the cysteine precursor, O-acetylserine. During sulphur deprivation, a preferential depletion of the pool of the indole-3-acetonitrile precursor glucobrassicin compared with that of total glucosinolates was noticed. In the absence of an external sulphate supply, plants developed longer roots with a higher number of lateral roots. The increased growth of the root system occurred at the expense of shoot growth which was retarded under conditions of sulphur starvation. Taken together, these results suggest that a regulatory loop appears to exist by which sulphate deficiency, through an increase in glucobrassicin turnover and nitrilase 3 accumulation, initiates the production of extra auxin leading to increased root growth and branching, thus allowing the root system to penetrate new areas of soil effectively to gain access to fresh supplies of sulphur.
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PMID:A role for nitrilase 3 in the regulation of root morphology in sulphur-starving Arabidopsis thaliana. 1196 96

Current human gene therapy relies on genetic modification of the patient's own cells. An alternate nonautologous approach is to use universal cell lines engineered to secrete therapeutic products. Protection with immunoisolation devices before implantation would allow the use of the same recombinant cell line for treating different patients, thus potentially lowering the cost of treatment. To study the properties of a mechanically stable synthetic biomaterial, hydroxyethyl methyacrylate-methyl methacrylate (HEMA-MMA) as the immuno-isolation device, we encapsulated recombinant mouse fibroblast cells engineered to secrete products ranging from 27 to 300 kDa in size (human growth hormone, mouse beta-hexosaminidase and beta-glucuronidase) in the presence or absence of the extracellular matrix Matrigel. Both viability and cell number in the microcapsules increased with time after encapsulation and cell morphology indicated viable cell growth, thus showing that the capsule membrane barrier was compatible with nutrient/waste exchange necessary for normal metabolic activity.The intracellular levels of these recombinant gene products were constant throughout the experimental period of 22 days in the presence or absence of Matrigel, thus demonstrating that the microenvironment did not lead to downregulation of the transgenes. However, the extracellular levels of the gene products secreted from the cells and trapped within the microcapsules were dependent on the molecular size of the product and presence of Matrigel. With the 27-kDa human growth hormone, the presence of Matrigel caused its retention within this intracapsular space, but its release from the microcapsules to the culture medium was not impeded. With the 120-kDa beta-hexosaminidase or the 300-kDa beta-glucuronidase, they were retained within the microcapsule space regardless of the presence or absence of Matrigel, and their passage from the microcapsules to the media was totally blocked. In conclusion, the HEMA-MMA microcapsules are supportive of recombinant cell growth and maintained their molecular cutoff at approximately 100 kDa. Inclusion of extracellular matrix was unable to improve cell growth and may impede the exit of some gene products.
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PMID:Secretion of recombinant proteins from hydroxyethyl methacrylate-methyl methacrylate capsules. 1862 60

Non-autologous somatic gene therapy is an alternate approach to delivering recombinant gene products through implantation of a "universal" donor cell line engineered to produce a therapeutic gene product. The cells are immunologically isolated by enclosure in immunoprotective microcapsules fabricated from alginate-poly-L-lysine-alginate. The molecular weight cutoff of these microcapsules was thought to be <100 kd, thus, excluding the immunoglobulins. However, when such microcapsules are fabricated to enclose cells, they show a higher permeability threshold than expected. The secretion rates of recombinant gene products ranging from 21 through 150 to 300 kd (human growth hormone, rat serum albumin, human arylsulfatase A, human immunoglobulin, mouse beta-hexosaminidase, mouse beta-glucuronidase) were similar between the nonencapsulated and encapsulated recombinant cells with the exception of the largest molecular species, the 300-kd beta-glucuronidase. Its secretion was reduced about eightfold after encapsulation. Increasing the thickness of the membrane by prolonging the coating time with poly-L-lysine did not provide a lower molecular weight cutoff. An additional coating with alginate, however, reduced the leakage of the larger molecular species, but the effect was short lived: After 2 weeks in culture, the double- and single-coated microcapsules were equally permeable. Both the increased poly-L-lysine and alginate coating were detrimental to the long-term viability and proliferation of the encapsulated cells. Hence, immunoisolation of encapsulated cells with alginate-poly-L-lysine-alginate microcapsules cannot provide a molecular weight cutoff below 300 kd. (c) 1996 John Wiley & Sons, Inc.
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PMID:Permeability of alginate microcapsules to secretory recombinant gene products. 1862 20


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