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)

Vascular disease in diabetics could arise in part from altered vessel wall catebolism. Specific activities of hydrolases in aortic smooth muscle cells from rats with streptozotocin-induced diabetes were measured. Enyzmes included: neutral alpha-glucosidase, alpha-mannosidase, and lysosomal N-acetyl beta-glucosaminidase, beta-galactosidase, cathepsin C, acid alpha-glucosidase, and acid cholesteryl esterase. After 4,8, and 11 weeks of diabetes, activities of all enzymes studied were decreased significantly in diabetic vessels, decreases ranging from 15% for cathepsin C to 62% for alpha-mannosidase. After 3 weeks of diabetes, insulin treatment for 1 week restored enzyme levels to normal. After 7 weeks of diabetes, 1 week of insulin treatment did not restore enzyme levels fully to normal (acid cholesteryl esterase was unchanged); 4 weeks of insulin did. Acid phosphatase and N-acetyl beta-glucosaminidase activities were reduced markedly in histochemical studies of diabetic aortas at all time periods and were restored by insulin treatment. Alloxan-induced diabetes gave results similar to those with streptozotocin. Significant decreases of aortic hydrolase activities, including those of lysosomes, occur in experimental diabetes mellitus and could contribute to accumulation of substrates in vascular smooth muscle cells.
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PMID:Hydrolase activities in the rat aorta. I. Effects of diabetes mellitus and insulin treatment. 14 80

To utilize gene therapy, we required an efficient method to transfect intact islets before their use in transplantation. The biolistic method transforms cells by bombarding them with microprojectiles coated with DNA. Once internalized, the DNA is solubilized and expressed. We used the firefly luciferase gene driven by the human cytomegalovirus immediate early promoter as a reporter construct in freshly isolated BALB/c mouse islets to compare the transfection efficiency using either the biolistic method, lipofection, or recombinant adenoviral infection (n=4 in each case). The biolistic method achieved, on average, a 35-fold higher level of luciferase activity than the lipofection method (mean +/- SEM: 42.6 +/- 14.2 vs. 1.1 +/- 0.2 relative light units (RLU)/islet). Adenoviral infection achieved, on average, a further 25-fold higher level of luciferase activity than the biolistic method (1136.0 +/- 542.0 RLU/islet). The average proportion of islets recovered 48 hr after the biolistic blast was 53% (n=20). The average number of dissociated cells found to express the foreign gene product using beta-galactosidase as a reporter construct was 3% (n=6). Furthermore, nontransformed and biolistically transformed islets responded similarly to an in vitro glucose challenge (stimulation index of insulin release at 20.0 mM glucose/insulin release at 2.8 mM glucose = 2.8 and 3.0, respectively, P=0.9). Syngeneic, biolistically transfected islets functioned to reverse the diabetic state when transplanted (500 islets) beneath the renal capsule of alloxan-induced diabetic BALB/c recipients (n=7). This methodology can achieve efficient transfection of pancreatic islets while preserving their function and thus holds promise for ex vivo gene therapy of isolated islets prior to transplantation.
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PMID:Successful biolistic transformation of mouse pancreatic islets while preserving cellular function. 866 98

The aim of this study was to establish and quantify changes in the activities of the some lysosomal enzymes and to determine the type of changes in the ultrastructure of the submandibular gland in rabbits caused during progression of diabetes. The experiment was conducted on 89 New Zealand rabbit males. Diabetes was induced by the intravenous administration of 10% alloxan solution at a dose of 10-mg/kg-body weight. On the seventh day after alloxan administration, the level of glucose in blood was determined. Rabbits were divided into five groups: intact (n=18), 21-day diabetes (n=18), 42-day diabetes (n=17), 90-day diabetes (n=19) and 180-day diabetes (n=17). From killed animals in each group, the submandibular glands were removed and fixed or stored. Enzyme activities were assayed by spectrophotometric methods using substrates (Sigma) which release 4-methyloumbeliferol when they react with the proteases. Fixation procedure was done according to standard methods. Semi-thin and ultra-thin specimens were prepared by use of clearly visible after 42 days of diabetes. Mitochondria were damaged, accumulation of large amounts of lipids in the intracellular spaces was observed. After 90 days the presence of vacuoli and swollen lysosomes were observed, some cells also contained myelin figures. After 180 days the greatest changes were observed in the blood vessels, which had thickened walls and were often occluded. We concluded that the total activity of acid phosphatase and beta-N-acetyl-glucosaminidase in the submandibular gland was correlated with the level of glucose but there was no correlation between total beta-galactosidase activity and the serum concentration level of glucose has been detected during course of diabetes. The activities of the free fractions of acid phosphatase, beta-galactosidase and beta-N-acetyl-glucosaminidase in the submandibular gland were higher than the bound fractions in all groups of rabbits. The changes in the ultrastructure of the submandibular gland were correlated with changes in serum glucose level and with lysosomal enzymes activities during progression of experimental diabetes in rabbits.
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PMID:Changes in the activity of some lysosomal enzymes and in the fine structure of submandibular gland due to experimental diabetes. 1074 71

Increased production of oxygen free radicals is an important mechanism of endothelial dysfunction in diabetes mellitus. Our goal was to test whether adenovirus (Ad)-mediated gene transfer of copper/zinc (CuZn) or manganese superoxide dismutase (Mn SOD) improves relaxation of diabetic vessels. The aortas from 9 alloxan-induced diabetic mellitus (DM) and 16 control rabbits were used. Control and DM rings were transduced ex vivo with Ad vectors encoding Mn SOD (AdMn SOD), CuZn SOD (AdCuZn SOD), beta-galactosidase (Ad(beta)gal), or diluents. In the absence of gene transfer, SOD activity was significantly increased in DM aortas. Transgene expression in DM AdCuZn SOD and DM AdMn SOD-transduced vessels was confirmed by Western blot analysis and by increased SOD activity (DM AdCuZn SOD, 76.2 +/- 9.3; DM AdMn SOD, 65.2 +/- 4.8; P < 0.05 vs. DM Ad(beta)gal; 50.9 +/- 4.4 U/mg protein). Superoxide production was increased in DM Ad(beta)gal-transduced aorta and relaxations to acetylcholine were impaired in these vessels. Gene transfer of CuZn SOD and Mn SOD corrected both of these defects. Thus Ad-mediated gene transfer CuZn and Mn SOD to the diabetic aorta improves endothelium-dependent relaxation.
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PMID:Gene transfer of superoxide dismutase isoforms reverses endothelial dysfunction in diabetic rabbit aorta. 1135 6