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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In order to understand any involvement of altered calcium functions in peroxidative membrane damage, the effect of a few chemicals, known to modify specific biological responses involving calcium related functions on mitochondrial swelling in vitro was studied. Histamine caused swelling, whereas antihistamines reduced calcium induced swelling. Anti-inflammatory agents aspirin and indomethacin did not affect the initial rapid phase of swelling but reduced the swelling during the later phase. The uncouplers of oxidative phosphorylation and electron transport chain blockers such as dinitrophenol (DNP), antimycin-A and rotenone reduced swelling and the respiratory inhibitors KCN and sodium azide completely abolished it. Trifluoperazine, an anti-calmodulin agent did not influence the initial phase of calcium induced swelling but in the subsequent phase swelling was reduced. c-AMP as well as calcium ionophores, calcimycin and lasalocid acid, potentiated swelling. Thus agents capable of modulating calcium functions could influence the in vitro swelling of mitochondria.
Mol Cell Biochem 1993 Jul 21
PMID:Influence of some biological response modifiers on swelling of rat liver mitochondria in vitro. 823 81

We have previously reported that the administration of metrazole (MTZ) produces a sequential, dose-dependent induction of c-fos and proenkephalin (Penk) gene expression in the rat hippocampus and adrenal. The adrenal is more sensitive to induction of these genes by MTZ. In the present study, we have compared the induction of c-fos and Penk in the hippocampus and adrenal, and examined the consequences of selected pharmacological manipulations. Treatment with LY274614, a competitive NMDA-receptor antagonist, blocked MTZ-induced convulsions and the MTZ-induction of c-fos and PPenk mRNAs in the hippocampus, and PPenk mRNA in the adrenal. However, in the adrenal the MTZ-induction of c-fos was only partially inhibited by LY274614. A combination of peripheral acting cholinergic antagonists (chlorisondamine plus methylatropine) prevented the MTZ-induction of adrenal c-fos and PPenk mRNA without significant alterations in the MTZ-induction of hippocampal c-fos mRNA or convulsions. Trifluoperazine, a calcium/calmodulin inhibitor, attenuated the MTZ-induction of c-fos mRNA while potentiating the MTZ-induction of PPenk mRNA in both the hippocampus and the adrenal. These results demonstrate that the MTZ induction of c-fos and Penk gene expression in the rat adrenal can be modulated by drugs acting in the CNS at NMDA receptors, in the periphery at postsynaptic cholinergic receptors and intracellularly at the calcium/calmodulin signal transduction pathway. Furthermore, we provide additional evidence that MTZ-induction of c-fos and Penk mRNAs can be dissociated by drugs acting at these sites.
Brain Res Mol Brain Res 1993 Oct
PMID:Metrazole induction of c-fos and proenkephalin gene expression in the rat adrenal and hippocampus: pharmacological characterization. 825 73

The major protein in the sarcoplasmic reticulum (SR) membrane is the Ca2+ transporting ATPase which carries out active Ca2+ pumping at the expense of ATP hydrolysis. The aim of this work was to elucidate the mechanisms by which oxidative stress induced by Fenton's reaction (Fe(2+)+H2O2-->HO.+OH-+Fe3+) alters the function of SR. ATP hydrolysis by both SR vesicles (SRV) and purified ATPase was inhibited in a dose-dependent manner in the presence of 0-1.5 mM H2O2 plus 50 microM Fe2+ and 6 mM ascorbate. Ca2+ uptake carried out by the Ca(2+)-ATPase in SRV was also inhibited in parallel. The inhibition of hydrolysis and Ca2+ uptake was not prevented by butylhydroxytoluene (BHT) at concentrations which significantly blocked formation of thiobarbituric acid-reactive substances (TBARS), suggesting that inhibition of the ATPase was not due to lipid peroxidation of the SR membrane. In addition, dithiothreitol (DTT) did not prevent inhibition of either ATPase activity or Ca2+ uptake, suggesting that inhibition was not related to oxidation of ATPase thiols. The passive efflux of 45Ca2+ from pre-loaded SR vesicles was greatly increased by oxidative stress and this effect could be only partially prevented (ca 20%) by addition of BHT or DTT. Trifluoperazine (which specifically binds to the Ca(2+)-ATPase, causing conformational changes in the enzyme) fully protected the ATPase activity against oxidative damage. These results suggest that the alterations in function observed upon oxidation of SRV are mainly due to direct effects on the Ca(2+)-ATPase. Electrophoretic analysis of oxidized Ca(2+)-ATPase revealed a decrease in intensity of the silver-stained 110 kDa Ca(2+)-ATPase band and the appearance of low molecular weight peptides (MW < 100 kDa) and high molecular weight protein aggregates. Presence of DTT during oxidation prevented the appearance of protein aggregates and caused a simultaneous increase in the amount of low molecular weight peptides. We propose that impairment of function of the Ca(2+)-pump may be related to aminoacid oxidation and fragmentation of the protein.
Mol Cell Biochem 1996 Jun 21
PMID:Oxidative damage to sarcoplasmic reticulum Ca(2+)-pump induced by Fe2+/H2O2/ascorbate is not mediated by lipid peroxidation or thiol oxidation and leads to protein fragmentation. 885 60

We report that histones H2A and H2B possess gonadotrophin-releasing activity in vitro and assess the signal transduction pathways involved in these effects. Perifused and incubated rat anterior pituitary (AP) cells were used, and luteinizing hormone (LH) and follicle stimulating hormone (FSH) were measured by RIA. Perifusion of cells with histone H2A (30 muM) or histone H2B (30 muM), markedly stimulated LH release but failed to elicit any FSH response. Cells incubated with 6 or 30 muM histone H2A showed a dose- and time-dependent stimulatory effect on bot LH and FSH release which was blocked by 1 muM peptide MB35, an 86-120 amino acid fragment of histone H2A. Incubation of pituitary cells with gonadotrophin-releasing hormone (GnRH) and histones H2A or H2B showed a stimulatory effect on LH and FSH release which was similar to the sum of the separate effects. Trifluoperazine as well as ethylene glycol bis(b-aminoethyl ether) N,N,N',N'-tetraacetic acid (EGTA), alone or in the presence of the calcium ionophore A23187, significantly reduced the response of AP cells to histones. Various cyclic adenosine monophosphate (cAMP) enhancers had no effect on histone-stimulated release of gonadotrophins in incubated AP cells. Our results confirm previous evidence that histones may act as hypophysiotrophic signals. Calcium- and diacylglycerol-associated pathways, but not cAMP, appear to participate in these effects.
Cell Mol Life Sci 1998 Mar
PMID:Gonadotrophin-releasing activity of histones H2A and H2B. 957 41

The effect of Ca2+-binding protein regucalcin on neutral phosphatase activity in rat brain cytosol was investigated. Phosphatase activity was assayed in a reaction mixture containing the cytosolic protein in the presence of phosphotyrosine, phosphoserine, and phosphothreonine. The presence of calcium chloride (10(-5) and 10(-4) M) in the enzyme reaction mixture caused a significant increase in phosphatase activity toward three phosphoaminoacids. The enzyme activity toward phosphoserine and phosphothreonine was significantly enhanced by the addition of calmodulin (1 or 5 microg/ml) in the presence of calcium (10(-5) M). Such an effect was not seen in the presence of phosphotyrosine. Trifluoperazine (2x10(-5) M), an antagonist of calmodulin, completely inhibited calcium (10(-5) M)-increased phosphatase activity toward phosphoserine and phosphothreonine, whereas it had no effect on the enzyme activity toward phosphotyrosine. Regucalcin (10(-9) M) significantly inhibited phosphatase activity toward three phosphoaminoacids without or with Ca2+ addition. The inhibitory effect of regucalcin (10(-10) and 10(-9) M) was also seen in the presence of Ca2+ (10(-5) M) and calmodulin (5 microg/ml). The presence of anti-regucalcin monoclonal antibody (20 or 50 ng/ml) in the enzyme reaction mixture caused a significant elevation of phosphatase activity toward three phosphoaminoacids; this effect was completely abolished by addition of regucalcin (10(-9) M). The present study suggests that the endogenous regucalcin has an inhibitory effect on Ca2+/calmodulin-dependent protein phosphatase activity in rat brain cytosol.
Int J Mol Med 1999 Jun
PMID:Inhibitory effect of regucalcin on Ca2+/calmodulin-dependent protein phosphatase activity in rat brain cytosol. 1034 Dec 92

Trifluoperazine (TFP), a phenothiazine antipsychotic agent with calmodulin antagonist property, induces DNA fragmentation in a dose- and time-dependent manner in PC12 cells. Various agents affecting calcium mediated intracellular signal transduction such as calcium chelators, calcium ionopores, inhibitors of phospholipase C, and activators/inhibitors of protein kinase C did not block TFP-induced DNA fragmentation. Some of these agents themselves induced DNA fragmentation in the conditions under which they were examined. However, cholera toxin (selective Gs activator), forskolin (adenylate cyclase activator) or dibutyryl cyclic AMP (cyclic AMP analogue) inhibited TFP-induced DNA fragmentation in a dose-dependent manner. These results suggest that it is not the calcium but the Gs and adenylate cyclase pathways that play an important role in TFP-induced DNA fragmentation in PC12 cells.
Mol Cells 1999 Dec 31
PMID:Inhibition of trifluoperazine-induced DNA fragmentation by cyclic AMP mediated signaling. 1067 25

Ecto-enzymes capable of hydrolyzing ATP and ADP (NTPDase) are present in the central nervous system of various species. In the present investigation we studied the synaptosomal NTPDase (ATP diphosphohydrolase, apyrase, E.C. 3.6.1.5) from fish, chicken and rats under different conditions and in the presence of several classical inhibitors. The cation concentration required for maximal activity was 0.5 mM for fish, 1.0 mM for chickens and 1.5 mM for rats with both substrates. The results showed that the pH optimum for all animal preparations was close to 8.0. The temperature used was 25-27 degrees C for fish and 35-37 degrees C for chicken and rat preparations. The inhibitors azide and fluoride only inhibited the preparation at high concentrations (10 mM). Lanthanum (0.1-0.4 mM), N-ethylmaleimide (0.4-3.0 mM) and ouabain (0.5-3.0 mM) had no effect on NTPDase activity from fish, chickens or rats. Orthovanadate (0.1-0.3 mM) only inhibited fish synaptosomal NTPDase. Trifluoperazine (0.05-0.2 mM) and suramin (0.03-0.3 mM) inhibited NTPDase at all concentrations tested. Suramin was the most potent compound in causing inhibition, presenting inhibition at 30 microM. Our results demonstrate that the synaptosomal NTPDase response to several factors is similar in fish, chickens and rats, and that the enzyme presents functional homology.
Comp Biochem Physiol B Biochem Mol Biol 2001 Apr
PMID:ATP and ADP hydrolysis in fish, chicken and rat synaptosomes. 1129 Apr 55

The role of regucalcin, a regulatory protein in intracellular signaling pathway, in the regulation of protein phosphatase activity in the heart muscle cytosol was investigated by using normal (wild-type) and regucalcin transgenic (TG) rats. Protein phosphatase activity was assayed in a reaction mixture containing the cytosolic protein in the presence of phosphotyrosine, phosphoserine, and phosphothreonine. The addition of calcium chloride (10 and 20 microM) in the enzyme reaction mixture caused a significant increase in protein phosphatase activity toward three phosphoaminoacids. Trifluoperazine (10 and 20 microM), an antagonist of calmodulin, completely inhibited calcium (10 microM) addition-increased protein phosphatase activity toward three phosphoaminoacids. Moreover, the calcium (10 microM)-increased enzyme activity toward phosphoserine and phosphothreonine was significantly enhanced by the addition of calmodulin (2.5 or 5 microg/ml). Such an enhancement was not seen in the presence of phosphotyrosine. Regucalcin (10(-9) and 10(-8) M) significantly inhibited protein phosphatase activity toward three phosphoaminoacids in the presence of ethylene glycol bis (2-aminoethlether) N,N,N',N'-tetraacetic acid (EGTA; 1 mM), without Ca2+ addition. The inhibitory effect of regucalcin (10(-10)-10(-8) M) was also seen in the presence of calcium chloride (10 microM). Western blot analysis showed a remarkable expression of regucalcin protein in the cytosol of heart of regucalcin TG female rats as compared with that of wild-type female rats. Protein phosphatase activity toward three phosphoaminoacids was significantly decreased in the heart cytosol of TG rats. The enhancing effect of calcium (10 microM) addition on protein phosphatase activity toward three phosphoaminoacids was not seen in the heart cytosol of TG rats. This study demonstrates that endogenous regucalcin plays a suppressive role in the regulation of protein phosphatase activity in rat heart cytoplasm.
Int J Mol Med 2004 Feb
PMID:Suppressive effect of regucalcin on protein phosphatase activity in the heart cytosol of normal and regucalcin transgenic rats. 1471 36

The early growth response gene-1 (Egr-1) is a tumor suppressor which plays an important role in cell growth, differentiation and apoptosis. Egr-1 has been shown to be down-regulated in many types of tumor tissues. Trifluoperazine (TFP), a phenothiazine class of antipsychotics, restored serum-induced Egr-1 expression in several cancer cell lines. We investigated the effect of Egr-1 expression on the TFP-induced inhibition of cell growth. Ectopic expression of Egr-1 enhanced the TFP-induced antiproliferative activity and downregulated cyclin D1 level in U87MG glioma cells. Our results suggest that antipsychotics TFP exhibits antiproliferative activity through up-regulation of Egr-1.
Exp Mol Med 2004 Aug 31
PMID:Implication of Egr-1 in trifluoperazine-induced growth inhibition in human U87MG glioma cells. 1536 58

We investigated NTPDase-like activity [ecto-nucleoside triphosphate diphosphohydrolases (E-NTPDases)] in liver and kidney membrane from silver catfish (Rhamdia quelen), chicken (Gallus gallus) and rat (Rattus norvegicus) under different conditions and in the presence of several inhibitors. The cation concentration required for maximal activity was 0.5, 1.5 and 2.0 mM for fish, chicken and rat liver, respectively (with ATP and ADP as substrates). The maximal activity in the kidney was observed at calcium concentrations of 0.5, 2.0, 1.5 mM (ATP) and 0.5, 1.5, 1.0 (ADP) for fish, chickens and rats, respectively. The results showed that the pH optimum for all animals and for the two tissues was close to 8.0. The temperature chosen was 25 degrees C for fish and 36 degrees C for chicken and rat preparations. Ouabain had no effect on the NTPDase-like activity of fish, chickens or rats. NTPDase activity was decreased in the presence of lanthanum in the chicken (ADP) and rat (ATP and ADP) liver. In the kidney, lanthanum inhibited fish ATP and rat ATP and ADP (0.2 mM) hydrolysis. N-ethylmaleimide (NEM) had an inhibitory effect on the kidney of all species at the concentration of 3.0 mM (ADP). Orthovanadate only inhibited fish membrane NTPDase; azide only inhibited the preparation at high concentrations (10 mM) and fluoride inhibited it at 10 mM (fish and chicken) and 5 mM (rat). Trifluoperazine (0.05-0.2 mM) and suramin (0.03-0.3 mM) inhibited NTPDase at all concentrations tested. These results suggest that NTPDase-like activity shows a different behavior among the vertebrate species and tissues studied. Additionally, we propose that NTPDase1 is the main enzyme present in this preparation.
Comp Biochem Physiol B Biochem Mol Biol 2004 Dec
PMID:ATP and ADP hydrolysis in the kidney and liver of fish, chickens and rats. 1558 3


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