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)

Delta toxin, one of at least four toxins produced by pathogenic strains of the skin bacterium Staphylococcus aureus, is an amphipathic polypeptide possessing hemolytic and cytolytic activity. Delta toxin stimulates high levels of phospholipase A2 activity in 3T3 mouse fibroblasts with concomitant synthesis and release of prostaglandins. Alpha toxin, another hemolytic toxin produced by strains of S. aureus, did not stimulate phospholipase A2 or prostaglandin release in these cells. Analysis of the release of lactate dehydrogenase and beta-galactosidase (cytoplasmic and lysosomal marker enzymes, respectively) from delta-toxin-treated cells indicated that cytolytic concentrations of the toxin damage the cell-surface membrane more extensively than lysosomal membranes. During a 30 min exposure, delta toxin stimulated 3T3 cells to hydrolyze up to 32% of the lipids biosynthetically labeled by incorporation of [3H]arachidonic acid. A relatively high percentage of the free arachidonic acid formed in delta-toxin-treated 3T3 cells was converted to prostaglandins (up to 41.3% and 8.3% converted to chromatographically identifiable prostaglandins E2 and F2 alpha, respectively, in 30 min), with optimal conversion occurring at sublytic toxin concentrations. The degree of activation of phospholipase A2 in 3T3 cells by a range of concentrations of delta toxin correlates with cytotoxicity assessed by failure to exclude trypan blue dye. Analysis of the calcium dependency of the toxin-activated phospholipase A2 was consistent with a cell-surface, Ca2+-dependent enzyme. The phospholipase A2 exhibits a degree of specificity for substrate lipids containing polyunsaturated fatty acid residues which can serve as precursors for prostaglandin formation. Enzymatic activity was not inhibited by diisopropylfluorophosphate (5 mM), N-ethylmaleimide (5 mM) or p-bromophenacylbromide (0.1 mM). Delta toxin did not activate detectable phospholipase A2 in subcellular preparations containing plasma membrane.
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PMID:Staphylococcal delta toxin stimulates endogenous phospholipase A2 activity and prostaglandin synthesis in fibroblasts. 721 81

In the present study, the motilin receptor was characterized by enzymatic digestion studies and by solubilization of the motilin-receptor complex from prelabeled membranes using the anionic detergent cholic acid. Motilin binding was significantly decreased by preincubation of membranes of rabbit antral tissue with trypsin, phospholipase A2, C, D, dithiothreitol and 2-mercaptoethanol but not by neuraminidase and beta-galactosidase. Treatment of prelabeled membranes with 1% cholic acid resulted in solubilization of 24 +/- 5% of the proteins and 65 +/- 3% of the radioactivity. The latter was for 77 +/- 4% due to the presence of the motilin-receptor complex as estimated with PEG-precipitation. Upon gel-filtration on Superose 6 the complex partially dissociated but 43 +/- 3% eluted with macromolecular components in the void volume. This peak was not detected when membranes were first incubated with unlabeled motilin. Further disaggregation was accomplished by the addition of 0.5 M NaCl to the elution buffer. The chromatographic profile then showed a peak of about 370 kDa and a second one of 100 kDa. The latter value probably reflects the molecular mass of a single 125I-motilin-receptor-complex.
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PMID:Solubilization and characterization of motilin-receptor complexes from rabbit antral smooth muscle tissue. 851 70

Endogenously released or exogenously administered glucocorticosteroids are relevant hormones for controlling inflammation. Only 11beta-hydroxy glucocorticosteroids, but not 11-keto glucocorticosteroids, activate glucocorticoid receptors. Since we found that glomerular mesangial cells (GMC) express 11beta-hydroxysteroid dehydrogenase 1 (11beta-OHSD1), which interconverts 11-keto glucocorticosteroids into 11beta-hydroxy glucocorticosteroids (cortisone/cortisol shuttle), we explored whether 11beta-OHSD1 determines the antiinflammatory effect of glucocorticosteroids. GMC exposed to interleukin (IL)-1beta or tumor necrosis factor alpha (TNF-alpha) release group II phospholipase A2 (PLA2), a key enzyme producing inflammatory mediators. 11beta-hydroxy glucocorticosteroids inhibited cytokine-induced transcription and release of PLA2 through a glucocorticoid receptor-dependent mechanism. This inhibition was enhanced by inhibiting 11beta-OHSD1. Interestingly, 11-keto glucocorticosteroids decreased cytokine-induced PLA2 release as well, a finding abrogated by inhibiting 11beta-OHSD1. Stimulating GMC with IL-1beta or TNF-alpha increased expression and reductase activity of 11beta-OHSD1. Similarly, this IL-1beta- and TNF-alpha-induced formation of active 11beta-hydroxy glucocorticosteroids from inert 11-keto glucocorticosteroids by the 11beta-OHSD1 was shown in the Kiki cell line that expresses the stably transfected bacterial beta-galactosidase gene under the control of a glucocorticosteroids response element. Thus, we conclude that 11beta-OHSD1 controls access of 11beta-hydroxy glucocorticosteroids and 11-keto glucocorticosteroids to glucocorticoid receptors and thus determines the anti-inflammatory effect of glucocorticosteroids. IL-1beta and TNF-alpha upregulate specifically the reductase activity of 11beta-OHSD1 and counterbalance by that mechanism their own proinflammatory effect.
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PMID:Tumor necrosis factor alpha and interleukin 1beta enhance the cortisone/cortisol shuttle. 922 48


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