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:1.11.1.7 (peroxidase)
65,474 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The regulatory mechanism of degranulation of guinea pig peritoneal eosinophils was studied by determination of eosinophil peroxidase (EPO) release. Beta-agonists, such as isoproterenol, salbutamol and fenoterol, effectively inhibited A23187-induced EPO release from guinea pig eosinophils. The inhibitory effects of beta-agonists were attenuated by pretreatment with either propranolol, a non-selective beta-antagonist, or ICI 118,551, a selective beta2-antagonist. Both theophylline and dibutyryl-cAMP (db-cAMP) also significantly inhibited A23187-induced EPO release. The inhibition of EPO release induced by db-cAMP was attenuated by pretreatment with KT5720, a protein kinase A inhibitor. In addition, calphostin C as well as cytochalasin D effectively inhibited A23187-induced EPO release. From the results of the present study, it was concluded that an increase in intracellular Ca2+ concentration may lead to exocytosis of eosinophil granules through activation of protein kinase C and microfilaments. Beta-agonists and theophylline were effective in inhibiting degranulation of eosinophils by increasing intracellular cAMP level coupled with the activation of protein kinase A.
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PMID:Regulatory mechanism of eosinophil peroxidase release from guinea pig eosinophils. 1100 Nov 74

YM976 is a novel and specific phosphodiesterase 4 inhibitor. In our previous report, we indicated that YM976 has less emetogenicity, a major adverse effect of PDE4 inhibitors, than rolipram. In the present study, we examined the antiasthmatic effects of YM976 in guinea pigs. YM976 orally administered exhibited inhibition of antigen-induced bronchoconstriction, airway plasma leakage, airway eosinophil infiltration, and airway hyperreactivity (AHR), with ED(50) values of 7.3, 5.7, 1.0, and 0.52 mg/kg, respectively. Rolipram also dose dependently suppressed these responses. Prednisolone suppressed eosinophil infiltration and AHR, whereas it failed to inhibit bronchoconstriction and plasma leakage. Theophylline moderately suppressed bronchoconstriction and edema, but neither eosinophil infiltration nor AHR. YM976 suppressed the peroxidase activity in the bronchoalveolar lavage fluid, and elevated the intracellular peroxidase activity and cAMP contents of infiltrated cells, suggesting that YM976 inhibited not only the infiltration but also the activation of leukocytes. In vitro studies revealed that YM976 potently suppressed eosinophil activation (EC(30) = 83 nM), and exerted a little relaxation on LTD(4)-precontracted tracheal smooth muscle (EC(50) = 370 nM). Rolipram exhibited a potent tracheal relaxation activity (EC(50) = 50 nM). In vivo studies indicated that the inhibitory effect of YM976 on LTD(4)-induced bronchospasm was marginal even at 30 mg/kg p.o., although rolipram significantly inhibited the bronchospasm at the same dose. These results suggested that YM976, unlike rolipram, showed the inhibition of antigen-induced airway responses due to anti-inflammatory effects, but not to direct tracheal relaxation. In conclusion, YM976 may have potential therapeutic value in the treatment of asthma through its anti-inflammatory activities.
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PMID:Antiasthmatic effect of YM976, a novel PDE4 inhibitor, in guinea pigs. 1125 41

We observed that the transcription of Saccharomyces cerevisiae cytoplasmic thiol peroxidase type II (cTPx II) (YDR453C) is regulated in response to various stresses (e.g. oxidative stress, carbon starvation, and heat-shock). It has been suggested that both transcription-activating proteins, Yap1p and Skn7p, regulate the transcription of cTPx II upon exposure to oxidative stress. However, a dramatic loss of transcriptional response to various stresses in yeast mutant strains lacking both Msn2p and Msn4p suggests that the transcription factors act as a principal transcriptional activator. In addition to two Yap1p response elements (YREs), TTACTAA and TTAGTAA, the presence of two stress response elements (STREs) (CCCCT) in the upstream sequence of cTPx II also suggests that Msn2p/Msn4p could control stress-induced expression of cTPx II. Analysis of the transcriptional activity of site-directed mutagenesis of the putative STREs (STRE1 and STRE2) and YREs (TRE1 and YRE2) in terms of the activity of a lacZ reporter gene under control of the cTPx II promoter indicates that STRE2 acts as a principal binding element essential for transactivation of the cTPx II promoter. The transcriptional activity of the cTPx II promoter was exponentially increased after postdiauxic growth. The transcriptional activity of the cTPx II promoter is greatly increased by rapamycin. Deletion of Tor1, Tor2, Ras1, and Ras2 resulted in a considerable induction when compared with their parent strains, suggesting that the transcription of cTPx II is under negative control of the Ras/cAMP and target of rapamycin signaling pathways. Taken together, these results suggest that cTPx II is a target of Msn2p/Msn4p transcription factors under negative control of the Ras-protein kinase A and target of rapamycin signaling pathways. Furthermore, the accumulation of cTPx II upon exposure to oxidative stress and during the postdiauxic shift suggests an important antioxidant role in stationary phase yeast cells.
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PMID:Msn2p/Msn4p act as a key transcriptional activator of yeast cytoplasmic thiol peroxidase II. 1182 10

The role of nongenomic action of estrogens on elicited catecholamine secretion and exocytosis kinetics was studied in perfused rat adrenals and in cultured bovine chromaffin cells. 17beta-Estradiol as well as the estrogen receptor modulators raloxifene and LY117018, but not 17alpha-estradiol, inhibited at the micromolar range the catecholamine output elicited by acetylcholine or high potassium. However, these agents failed to modify the secretion elicited by high Ca(2+) in glands treated with the ionophore A-23187 (calcimycin), suggesting that estrogens did not directly act on the secretory machinery. At the single cell level, estrogens modified the kinetics of exocytosis at nanomolar range. All of the drugs tested except 17alpha-estradiol produced a profound slowing down of the exocytosis as measured by amperometry. LY117018 also reduced the granule content of catecholamines. 17beta-Estradiol reduced the intracellular free Ca(2+) but only at micromolar concentrations, whereas nanomolar concentrations increased the cAMP levels. These effects were reproduced with the nonpermeable drug 17beta-estradiol-horseradish peroxidase and antagonized with nanomolar concentrations of the antiestrogen ICI 182,780 (fulvestrant). Our data suggest the presence of membrane sites that regulate both the exocytotic phenomenon and the total catecholamine release with high and low affinity, respectively.
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PMID:Nongenomic regulation of the kinetics of exocytosis by estrogens. 1196 Oct 67

Heme-binding protein 23 (HBP23), also termed peroxiredoxin I (Prx I), is an antioxidant protein that is induced by various oxidative stress stimuli. HBP23/Prx I has thioredoxin-dependent peroxidase activity and noncovalently binds the prooxidant heme with high affinity. To investigate the regulatory role of cellular phosphorylation and dephosphorylation events on hepatic HBP23/Prx I gene expression, primary cultures of rat hepatocytes were treated with okadaic acid (OA) which is a specific inhibitor of the serine threonine protein phosphatases 1 and 2A. In hepatocyte cultures HBP23/Prx I was highly expressed for up to 5 days and, both protein and mRNA levels of HBP23/Prx I were induced by OA. The time kinetics of OA-dependent HBP23/Prx I mRNA upregulation were coordinate to that of heme oxygenase (HO)-1, which is the inducible isoform of the rate-limiting enzyme of heme-degradation. In contrast to HO-1, however, induction of HBP23/Prx I mRNA by OA was downregulated by dibutyryl-cAMP, and was enhanced by the specific protein kinase A inhibitors KT5720 and H-89. HBP23/Prx I induction by OA occurred on the transcriptional level as determined by studies with actinomycin D and nuclear run-off assays.
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PMID:Induction of heme-binding protein 23/peroxiredoxin I gene expression by okadaic acid in cultured rat hepatocytes. 1204 73

1-cys peroxiredoxin (1-cys Prx), the only member of a Prx subfamily that contains a single conserved cysteine residue, is abundant in lung. This bifunctional protein has both glutathione peroxidase and phospholipase A2 activities compatible with a role both in protection against lung oxidant injury and also in lung phospholipid metabolism. Here we studied the developmental expression of 1-cys Prx in rat lungs and hormonal effects on protein expression in human and rat lung cells. There was little change in 1-cys Prx expression during the prenatal period, but a marked increase in expression immediately after birth. Enzymatic (peroxidase and phospholipase) activities increased gradually after birth and reached adult level at 7-14 postnatal days. Expression of the protein was induced in the presence of dexamethasone (Dex) in cultured human and rat lung epithelial cells and also was upregulated in neonatal rat lung in vivo. cAMP treatment had no effect on expression, although there was a modest synergistic effect when combined with Dex in human fetal lung epithelial cells. The increased expression of 1-cys Prx at birth may be important for surfactant phospholipid turnover related to the phopholipase A2 activity of the protein and for antioxidant defense based on its peroxidase function.
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PMID:Regulation of 1-cys peroxiredoxin expression in lung epithelial cells. 1215 15

Endocrine-disrupting chemicals (EDCs) are hormone-like agents present in the environment that alter the endocrine system of wildlife and humans. Most EDCs have potencies far below those of the natural hormone 17beta-E2 when acting through the classic estrogen receptors (ERs). Here, we show that the environmental estrogen Bisphenol-A and the native hormone 17beta-E2 activate the transcription factor, cAMP-responsive element binding protein (CREB) with the same potency. Phosphorylated CREB (P-CREB) was increased after only a 5-minute application of either BPA or 17beta-E2 in a calcium-dependent manner. The effect was reproduced by the membrane-impermeable molecule E2 conjugated to horseradish peroxidase (E-HRP). The increase in P-CREB was not modified by the anti-estrogen ICI 182,780. Therefore, low-dose of BPA activates the transcription factor CREB via an alternative mechanism, involving a non-classical membrane estrogen receptor. Because these effects are elicited at concentrations as low as 10(-9) M, this observation is of environmental and public health relevance.
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PMID:Low doses of the endocrine disruptor bisphenol-A and the native hormone 17beta-estradiol rapidly activate transcription factor CREB. 1220

We investigated the role of endogenous redox activity in regulating the signal transduction pathway leading to tyrosine phosphorylation in mouse spermatozoa. Endogenous redox activity was monitored using a luminol-peroxidase chemiluminescent probe. Chemiluminescence increased in spermatozoa that were actively undergoing cAMP-mediated tyrosine phosphorylation events associated with capacitation and was inhibited in a dose-dependent manner by addition of catalase or diphenylene iodonium, both of which also inhibited tyrosine phosphorylation within the cell at points downstream of cAMP. Excluding bicarbonate from the incubation medium reduced the redox activity of sperm by 80-90% and dramatically reduced tyrosine phosphorylation. This study provides the first evidence that tyrosine phosphorylation associated with capacitation in mouse spermatozoa is redox regulated by a flavinoid-containing enzyme involving mediation by hydrogen peroxide. Bicarbonate regulated the redox activity of mouse spermatozoa, and this regulation may contribute to the impact of this anion on tyrosine phosphorylation during capacitation of mouse spermatozoa.
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PMID:Endogenous redox activity in mouse spermatozoa and its role in regulating the tyrosine phosphorylation events associated with sperm capacitation. 1267 70

Persistent elevations of cAMP levels are generally accompanied by an inhibition of granulocyte functions. Phosphodiesterases play a critical role in regulating intracellular levels of cAMP. The expression of three isoforms of type 4 cAMP-specific phosphodiesterase (PDE4) in neutrophils suggests diversity of isoform localization and targeting in regulating cell function. The sites of cAMP regulation in granulocytes by the PDE4A isoform were investigated by immunoelectron microscopy. PDE4A was localized uniformly in all granule classes of eosinophils, but was restricted in neutrophils to a subset of myeloperoxidase (MPO)-containing granules that were round or elongated with a central crystalloid core. Granulocytes were stimulated with fMLP to investigate the sites of PDE4A targeting during cell activation. In neutrophils, fMLP induced a rapid (1 min) translocation of granules containing PDE4A to the plasmalemma, where some PDE4A and MPO were exocytosed. In these cells, PDE4A labeling within granules was focal and no longer homogeneous. While immunogold labeling of PDE4A was reduced after fMLP stimulation, staining of MPO-containing granules remained high. Extracellular release of PDE4A was also observed in eosinophils stimulated with fMLP. Morphometry revealed that Au labeling was significantly reduced within 1 min, and that there was a shift in PDE4A localization within eosinophil granules from the crystalline core to the matrix. Fluctuations of cAMP levels and ectoprotein kinase activity with PKA properties occur in blood under normal and pathological conditions. The exclusive localization of PDE4A within granules of neutrophils and eosinophils suggests that PDE4A may function to downregulate cAMP signaling at the cell membrane and/or in the extracellular space at the time of granule release.
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PMID:Type 4A cAMP-specific phosphodiesterase is stored in granules of human neutrophils and eosinophils. 1276 7

Of the many examples of oscillatory kinetic behaviour known, several are briefly reviewed, including those of glycolysis, the peroxidase-oxidase reaction and oscillations in cellular calcium concentration. It is shown that simple mathematical models employing allosteric rate laws are sufficient to explain the instability of the steady state and the appearance of sustained oscillations. The cAMP-signalling systems of cellular slime moulds and the dynamics of intracellular calcium oscillations illustrate the importance of such oscillophores to inter- and intra-cellular communication and differentiation.
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PMID:Implications of enzyme kinetics. 1277 91


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