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)

We have investigated the effect of the heat shock response on the leukotriene generation, chemotaxis, and generation of oxygen radicals of human polymorphonuclear granulocytes (PMNs) by preincubating the PMNs at 42 degrees C. Subsequently, the different test systems were performed at 37 degrees C. As we confirmed by the release of lactate dehydrogenase and beta-glucuronidase the elevated temperatures did not result in cytotoxic or degranulating processes. After heat shock treatment the generation of leukotrienes induced by the Ca(++)-ionophore A23187, fMLP or opsonized zymosan was inhibited in a time and temperature dependent manner (preincubation phase) as was measured by HPLC-analysis. In contrast, the conversion of 14C-arachidonic acid revealed the generation of LTB4, 5-HPETE and 5-HETE solely as a result of the preincubation at 42 degrees C without any further stimulation. In addition, the chemiluminescence response induced by opsonized zymosan and the chemotaxis against C5a and LTB4 was clearly inhibited after heat shock treatment. With regard to enzyme activities of the heat treated PMNs the protein kinase C activities were enhanced whereas the LTD4-dipeptidase and the LTB4-omega-hydroxylase were not affected.
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PMID:Heat shock induces alterations of the lipoxygenase pathway in human polymorphonuclear granulocytes. 251 49

The lipoxygenation of arachidonic acid in basophils, mastocytoma cells, and other leukocytes generates the unstable intermediate 5-hydroperoxy-eicostaetraenoic acid, which is converted in part to a series of complex hydroxy-eicosatetraenoic acids (HETEs) with additional polar substituents and 3 conjugated double bonds. One of the products, 5,12-di-HETE, is chemotactic for human neutrophils in vitro at a concentration as low as 3 ng/ml and evokes a maximal neutrophil chemotactic response at 30 ng/ml, as compared to 1000 ng/ml for 5-HETE and 10,000 to 20,000 ng/ml for 11-HETE and 12-HETE. In contrast, other products in the same series, such as the slow reacting substance 5-hydroxy-6-glutathionyl-eicosatetraenoic acid (leukotriene C), and the platelet-derived 8,9,12-trihydroxy-eicosatrienoic acid and 8,11,12-trihydroxy-eicosatrienoic acid exhibited only marginal neutrophil chemotactic activity. Only 5,12-di-HETE released significant quantities of beta-glucuronidase and lysozyme from the neutrophils, but the maximal level of enzyme release was far less than that for the chemotactic fragment of C5 and the formyl-methionyl peptides.
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PMID:The human PMN leukocyte chemotactic activity of complex hydroxy-eicosatetraenoic acids (HETEs). 741 Aug 54

2,3,5-Trimethyl-6-(3-pyridylmethyl)1,4-benzoquinone (CV-6504) is an effective inhibitor of the growth of established murine adenocarcinomas (MACs) and is shortly to enter clinical investigation. When administered to mice bearing the MAC16 tumour, CV-6504 rapidly disappeared from the plasma and tissues and there was an accumulation of the sulphate and glucuronide metabolites. After 24 h, the concentration of free CV-6504 in the tumour (3.3 microM) was higher than that in the liver (0.24 microM) and equal to the IC50 value for the inhibition of the growth of MAC16 cells in vitro (3 microM). The concentration of glucuronide and sulphate metabolites in both tumour and liver decreased with time. Both the MAC16 tumour and the liver possessed similar beta-glucuronidase activity, which could account for the accumulation of free CV-6504. Although the sulphate and glucuronide conjugates of CV-6504 were ineffective inhibitors of the growth of MAC13 cells in vitro at concentrations up to 100 microM, in vivo at a concentration of 50 mg kg-1 day-1 the conjugates produced a similar anti-tumour effect to CV-6504 at a concentration of 5 mg kg-1 day-1. The MAC13 tumour possessed both beta-glucuronidase and sulphatase activity capable of converting the sulphate and glucuronide conjugates to free CV-6504. Using MAC13 cells ex vivo, CV-6504 inhibited conversion of arachidonic acid to 5-, 12- and 15-hydroxyeicosatetraenoic acids (HETE). The percentage reduction in formation of 12- and 15-HETE exceeded that of 5-HETE. Inhibition of HETE formation may be responsible for the anti-tumour activity of CV-6504.
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PMID:Metabolism and pharmacokinetics of the anti-tumour agent 2,3,5-trimethyl-6-(3-pyridylmethyl)1,4-benzoquinone (CV-6504). 891 28