Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.2.1.31 (beta-glucuronidase)
 7,680 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

3-(5'-Hydroxymethyl-2'-furyl)-1-benzyl indazole (YC-1), a novel type of soluble guanylyl cyclase (sGC) activator, is useful in investigating the signaling of cGMP and may provide a new approach for treating cardiovascular diseases. Herein, YC-1 was demonstrated to inhibit the generation of superoxide anion (O2-) and the release of beta-glucuronidase release, to diminish the membrane-associated p47phox and to accelerate resequestration of cytosolic calcium in formyl-l-methionyl-l-leucyl-l-phenylalanine-activated human neutrophils. YC-1 not only directly promoted sGC activity and cGMP formation but also dramatically potentiated sodium nitroprusside-induced sGC activity and cGMP formation in human neutrophils. However, the synergistic increase in the amount of cGMP was inconsistent with its cellular response. Moreover, neither an sGC inhibitor nor protein kinase G inhibitors reversed the inhibitory effect of YC-1. Interestingly, YC-1 also increased the cAMP concentration and protein kinase (PK)A activity. The inhibitory effect of YC-1 was significantly enhanced by prostaglandin (PG)E1 and isoproterenol, and almost abolished by PKA inhibitors. These results show that cAMP, but not cGMP, mediates the YC-1-induced inhibition of human neutrophils. YC-1 increased the PGE1- and forskolin-induced but not 3-isobutyl-1-methylxanthine-produced cAMP formation, suggesting inhibition of phosphodiesterase. These findings thus reveal novel mechanism-mediated anti-inflammatory properties of YC-1 in human neutrophils, which can influence the progression of cardiovascular disease. cAMP, but not cGMP, plays an important role in the regulation of respiratory burst and degranulation in human neutrophils.
 ...
PMID:Soluble guanylyl cyclase activator YC-1 inhibits human neutrophil functions through a cGMP-independent but cAMP-dependent pathway. 1464 72

Demonstrating 1,25(OH)2D3-stimulated calcium uptake in isolated chick intestinal epithelial cells has been complicated by simultaneous enhancement of both uptake and efflux. We now report that in intestinal cells of adult birds, or those of young birds cultured for 72 h, 1,25(OH)2D3-stimulates 45Ca uptake to greater than 140% of corresponding controls within 3 min of addition. Such cells have lost hormone-stimulated protein kinase C (PKC) activity, believed to mediate calcium efflux. To further test this hypothesis, freshly isolated cells were preincubated with calphostin C, and calcium uptake monitored in the presence or absence of steroid. Only cells treated with the PKC inhibitor demonstrated a significant increase in 45Ca uptake in response to 1,25(OH)2D3, relative to corresponding controls. In addition, phorbol ester was shown to stimulate efflux, while forskolin stimulated uptake. To further investigate the mechanisms involved in calcium uptake, we assessed the role of TRPV6 and its activation by beta-glucuronidase. beta-Glucuronidase secretion from isolated intestinal epithelial cells was significantly increased by treatment with 1,25(OH)2D3, PTH, or forskolin, but not by phorbol ester. Treatment of cells with beta-glucuronidase, in turn, stimulated 45Ca uptake. Finally, transfection of cells with siRNA to either beta-glucuronidase or TRPV6 abolished 1,25(OH)2D3-enhanced calcium uptake relative to controls transfected with scrambled siRNA. Confocal microscopy further indicated rapid redistribution of enzyme and calcium channel after steroid. 1,25(OH)2D3 and PTH increase calcium uptake by stimulating the PKA pathway to release beta-glucuronidase, which in turn activates TRPV6. 1,25(OH)2D3-enhanced calcium efflux is mediated by the PKC pathway.
 ...
PMID:Membrane receptor-initiated signaling in 1,25(OH)2D3-stimulated calcium uptake in intestinal epithelial cells. 1877 29