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:3.6.1.3 (ATPase)
65,361 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The development of the mammalian heart is characterized by substantial changes in myocardial performance. We studied the ontogeny of myocardial function with and without various inotropic interventions in the developing isolated, antegrade-perfused rabbit heart (2d, 8d, 14d, 28d, n = 96). Myocardial function was related to the protein expression of the sarcolemmal Na(+)-Ca2+ exchanger and to the sarcoplasmic Ca(2+)-ATPase. In neonatal hearts an age-dependent increase in maximal developed pressure velocity (dP/dtmax) by 45% and peak negative pressure velocity (dP/ dtmin) by 75% within days 2 to 8 were observed. In response to inotropic intervention with isoproterenol, ouabain, calcium and the Na(+)-channel modulator BDF 9148, dP/dtmax and dP/dtmin increased in a concentration dependent manner. Significant differences between neonatal, juvenile and adult hearts could be demonstrated in a repeated measurement ANOVA model on the concentration-response curves for BDF 9148 (dP/dtmax and dP/dtmin), ouabain (dP/dtmin) and calcium (dP/dtmin), but not for isoproterenol. At the maximum isoproterenol concentration of 1 micromol/l, the increase in dP/dtmax and dP/dtmin was significantly higher in adult compared to neonatal hearts (t-test, p < 0.01). The significant decline of the Na(+)-Ca2+ exchanger protein expression from neonatal (1822 +/- 171) to adult hearts (411 +/- 96 S.E.M. [units per 20 microg protein], p < 0.01) was related to an increase in myocardial function (dP/dtmax r = 0.63, p < 0.01, dP/dtmin r = 0.62, p < 0.01). Contractility, relaxation and the observed positive inotropic effects were in general significantly lower in neonatal compared to adult hearts. In the individual heart an increase in contractility and relaxation was related to a decrease in Na(+)-Ca2+ exchanger expression.
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PMID:Effects of different inotropic interventions on myocardial function in the developing rabbit heart. 1199 79

The isoprenoid pathway produces three key metabolites--endogenous digoxin, dolichol, and ubiquinone. It was considered pertinent to assess the pathway in inflammatory bowel disease (ulcerative colitis and regional ileitis). Since endogenous digoxin can regulate neurotransmitter transport, the pathway and the related cascade were also assessed in individuals with differing hemispheric dominance to find out the role of hemispheric dominance in its pathogenesis. All the patients with inflammatory bowel disease were right-handed/left hemispheric dominant by the dichotic listening test. The following parameters were measured in patients with inflammatory bowel disease and in individuals with differing hemispheric dominance: (1) plasma HMG CoA reductase, digoxin, dolichol, ubiquinone, and magnesium levels; (2) tryptophan/tyrosine catabolic patterns; (3) free-radical metabolism; (4) glycoconjugate metabolism; and (5) membrane composition and RBC membrane Na+-K+ ATPase activity. Statistical analysis was done by ANOVA. In patients with inflammatory bowel disease there was elevated digoxin synthesis, increased dolichol and glycoconjugate levels, and low ubiquinone and elevated free radical levels. There was also an increase in tryptophan catabolites and a reduction in tyrosine catabolites. There was an increase in cholesterol:phospholipid ratio and a reduction in glycoconjugate level of RBC membrane in these groups of patients. Inflammatory bowel disease is associated with an upregulated isoprenoid pathway and elevated digoxin secretion from the hypothalamus. This can contribute to immune activation, defective glycoprotein bowel antigen presentation, and autoimmunity and a schizophreniform psychosis important in its pathogenesis. The biochemical patterns obtained in inflammatory bowel disease is similar to those obtained in left-handed/right hemispheric dominant individuals by the dichotic listening test. But all the patients with peptic ulcer disease were right-handed/left hemispheric dominant by the dichotic listening test. Hemispheric chemical dominance has no correlation with handedness or the dichotic listening test. Inflammatory bowel disease occurs in right hemispheric chemically dominant individuals and is a reflection of altered brain function.
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PMID:Hypothalamic digoxin, hemispheric chemical dominance, and inflammatory bowel disease. 1295 41

Antioxidant depletion is believed to be a mechanism involved in the pathophysiology of several upper gastrointestinal disorders, and H, K-ATPase inhibitors can alter free radical production by neutrophils. We hypothesized that the H, K-ATPase inhibitor esomeprazole magnesium would decrease gut free radical production with a concomitant increase in gut total antioxidant capacity. A/J mice (n = 10/group) received either vehicle (control) or one of three concentrations of esomeprazole magnesium in vehicle by once-daily gavage for 10 days. Using tissue extracts from stomach and colon, total antioxidant capacity, lipid peroxide levels, and constitutive Cu/Zn-superoxide dismutase were measured using validated assays. There was a dose-related increase in total antioxidant capacity (analysis of variance, P < 0.001) in stomach, but there was no change in the colon. In the assessment of free radical production, there was a trend toward decreased lipid peroxide levels in stomach from mice receiving esomeprazole. In stomach, Cu/Zn-superoxide dismutase activity was increased (ANOVA: p=.03) in mice receiving esomeprazole. In conclusion, gastric total antioxidant capacity and Cu/Zn-superoxide dismutase activity are increased by esomeprazole, and these changes may result in part from decreased free radical production. The present results support the notion that the pharmacological effects of this agent on upper intestinal tissue are more complex than previously thought, and appear to involve both enzymatic and nonenzymatic tissue antioxidants.
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PMID:Effect of the H, K-ATPase inhibitor, esomeprazole magnesium, on gut total antioxidant capacity in mice. 1535 Sep 83

Myosin heavy chain (MHC) isoforms alpha and beta have intrinsically different ATP hydrolysis activities (ATPase) and therefore cross-bridge cycling rates in solution. There is considerable evidence of altered MHC expression in rodent cardiac disease models; however, the effect of incremental beta-MHC expression over a wide range on the rate of high-strain, isometric cross-bridge cycling is yet to be ascertained. We treated male rats with 6-propyl-2-thiouracil (PTU; 0.8 g/l in drinking water) for short intervals (6, 11, 16, and 21 days) to generate cardiac MHC patterns in transition from predominantly alpha-MHC to predominantly beta-MHC. Steady-state calcium-dependent tension development and tension-dependent ATP consumption (tension cost; proportional to cross-bridge cycling) were measured in chemically permeabilized (skinned) right ventricular muscles at 20 degrees C. To assess dynamic cross-bridge cycling kinetics, the rate of force redevelopment (ktr) was determined after rapid release-restretch of fully activated muscles. MHC isoform content in each experimental muscle was measured by SDS-PAGE and densitometry. alpha-MHC content decreased significantly and progressively with length of PTU treatment [68 +/- 5%, 58 +/- 4%, 37 +/- 4%, and 27 +/- 6% for 6, 11, 16, and 21 days, respectively; P < 0.001 (ANOVA)]. Tension cost decreased, linearly, with decreased alpha-MHC content [6.7 +/- 0.4, 5.6 +/- 0.5, 4.0 +/- 0.4, and 3.9 +/- 0.3 ATPase/tension for 6, 11, 16, and 21 days, respectively; P < 0.001 (ANOVA)]. Likewise, ktr was significantly and progressively depressed with length of PTU treatment [11.1 +/- 0.6, 9.1 +/- 0.5, 8.2 +/- 0.7, and 6.2 +/- 0.3 s(-1) for 6, 11, 16, and 21 days, respectively; P < 0.05 (ANOVA)] Thus cross-bridge cycling, under high strain, for alpha-MHC is three times higher than for beta-MHC. Furthermore, under isometric conditions, alpha-MHC and beta-MHC cross bridges hydrolyze ATP independently of one another.
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PMID:Impact of beta-myosin heavy chain isoform expression on cross-bridge cycling kinetics. 1547 82

Ambient fine particulate matter (PM2.5, particulates with an aerodynamic diameter < or = 2.5 microm) can suppress alveolar macrophage (AM) functions, but the data concerning the effects of blowing sand PM2.5 on AMs remain limited. The aim of the present study is to investigate the influences of blowing sand PM2.5 on AM plasma membranes and intracellular calcium ion concentration ([Ca2+]i), and explore the mechanisms of the observed toxicological effects. The samples of normal PM2.5 (collected on sunshiny and non-blowing sand days) and blowing sand PM2.5 were collected in Wuwei city, Gansu Province, China. After AMs from rat bronchoalveolar lavage fluid (BALF) were treated in vitro for 4 h with the suspensions of these samples, the cell viability, plasma membrane permeability and fluidity, cytosolic free Ca2+ levels, and oxidative stress were examined. It was observed a dose-dependent decrease in cell viability, plasma membrane Ca2+Mg2+-dependent adenosinetriphosphatase (Ca2+Mg2+-ATPase) and Na+K+-dependent adenosinetriphosphatase (Na+K+-ATPase) activities, cellular glutathione (GSH) levels, fluorescence intensities of lipid probe 8-anilino-1-naphthalene-sulfonic acid (ANS) and fluorescence polarization of lipid probe 1,6-diphenyl-1,3,5-hexatriene (DPH) combined with cell membranes in the treatment groups of normal and blowing sand PM2.5 as compared to the control (saline group); and also observed a dose-dependent increase in the leakage of lactate dehydrogenase (LDH) and acid phosphatase (ACP), and intracellular [Ca2+]i and malondialdehyde (MDA) levels. These observations indicate blowing sand PM2.5, as similar to urban normal ones, could induce oxidative stress on AMs, enlarge plasma membrane permeability and membrane lipid fluidity, and elevate intracellular [Ca2+]i levels, resulting in cytotoxicity. A two-way ANOVA showed the toxic effects of normal and blowing sand PM2.5 on AMs were only relative to treatment dosages but not to dust types, suggesting the blowing sand PM2.5 whose airborne mass concentrations were much higher should be more harmful.
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PMID:Effects of blowing sand fine particles on plasma membrane permeability and fluidity, and intracellular calcium levels of rat alveolar macrophages. 1583

Although migraine is characterised by an abnormal cortical excitability level, whether the central nervous system is hyper- or hypo-excitable in migraine still remains an unsolved problem. The aim of our study was to compare the somatosensory evoked potential (SEP) recovery cycle, a marker of the somatosensory system's excitability, in a group of 15 children suffering from migraine without aura (MO) (mean age 11.7+/-1.6 years, five males, 10 females) and 10 control age-matched subjects (CS) (mean age 10.9+/-2.1 years, six males, four females). We calculated the SEP's latency and amplitude modifications after paired electrical stimuli at 5, 20 and 40 ms interstimulus intervals (ISIs), comparing it with a single stimulus condition assumed as the baseline. In MO patients, the amplitudes of the cervical N13 and of the cortical N20, P24 and N30 responses at 20 and 40 ms ISIs showed a higher recovery than in CS (two-way ANOVA, P<0.05). Since, the SEP recovery cycle depends on the inhibitory interneuron function, our findings suggest that a somatosensory system disinhibition takes place in migraine. This is a generalized phenomenon, not limited to the cerebral cortex, but concerning also the cervical grey matter. The SEP recovery cycle reflects the intracellular concentration of Na(+), therefore, the shortened recovery cycle in our MO patients suggests a high level of intracellular Na(+) and a consequent depolarized resting membrane potential, possibly due to an impaired Na(+) -K(+) ATPase function in migraine.
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PMID:Multilevel somatosensory system disinhibition in children with migraine. 1620 23

A study was conducted to investigate the in vitro toxicities of dust storm particulate matter with an aerodynamic diameter < or = 2.5 microm (PM(2.5)) on rat alveolar macrophages (AM). This was based on the ambient PM(2.5) collected in March 2004 from Baotou city, Inner Mongolia Autonomous Region, China. The particles were classified as normal (from sunshiny and clean days) and dust storm samples according to the dust storm classification, and the local weather and air quality monitoring data. The cell viability, levels of cellular thiobarbituric acid-reactive species (TBARS), glutathione (GSH), and cytosolic free calcium ions (Ca(2+)), and the plasma membrane ATPase activities and membrane lipid fluidity were determined 4h following the in vitro treatment of AM with differing dosages of the collected samples. Results revealed that dust storm PM(2.5) and their water-soluble fractions at high dosages generated oxidant stress on AM, induced leakage of lactate dehydrogenase (LDH), significantly decreased activities of plasma membrane Na(+)K(+)-ATPase, increased intracellular Ca(2+) levels, and led to significant alterations in membrane lipid fluidity, finally resulting in cytotoxicity. A two-way ANOVA showed that there was no significant difference in the above indices measured between the normal and dust storm PM(2.5), suggesting the deleterious effects of ambient PM(2.5) from Baotou city were based on the dose used rather than the type of particles. But due to a higher concentration of airborne PM(2.5) mass concentration in dust storm days than that in normal days, it concluded that during dust storm episodes, a much more serious effect on AM was imminent.
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PMID:In vitro responses of rat alveolar macrophages to particle suspensions and water-soluble components of dust storm PM(2.5). 1632 66

Mercury is widely distributed in the biosphere, and its toxic effects have been associated with human death and several ailments that include cardiovascular diseases, anemia, kidney and liver damage, developmental abnormalities, neurobehavioral disorders, autoimmune diseases, and cancers in experimental animals. At the cellular level, mercury has been shown to interact with sulphydryl groups of proteins and enzymes, to damage DNA, and to modulate cell cycle progression and/or apoptosis. However, the underlying molecular mechanisms of mercury toxicity remain to be elucidated. Our laboratory has demonstrated that mercury exposure induces cytotoxicity and apoptosis, modulates cell cycle, and transcriptionally activates specific stress genes in human liver carcinoma cells. The liver is one of the few organs capable of regeneration from injury. Dormant genes in the liver are therefore capable of reactivation. In this research, we hypothesize that mercury-induced hepatotoxicity is associated with the modulation of specific gene expressions in liver cells that can lead to several disease states involving immune system dysfunctions. In testing this hypothesis, we used an Affymetrix oligonucleotide microarray with probe sets complementary to more than 20,000 genes to determine whether patterns of gene expressions differ between controls and mercury (1-3 microg/mL) treated cells. There was a clear separation in gene expression profiles between controls and mercury-treated cells. Hierarchical cluster analysis identified 2,211 target genes that were affected. One hundred and eighty-eight of these genes were up-regulated, among which forty eight were significant (p = 0.001) with greater than a two-fold change difference in the concentration range (1-3 microg/mL) of mercury-treated cells; twelve genes were moderately over-expressed with an increase of more than one fold (p = 0.004). 2,023 genes were down-regulated with only forty of them reaching statistically significant decline at p = 0.05 according to the Welch's ANOVA/Welch's t-test. Further analyses of affected genes identified genes located on all human chromosomes with higher than normal effects on genes found on chromosomes 1-14, 17-20 (sex-determining region Y)-box18SRY, 21 (splicing factor, arginine/serine-rich 15 and ATP-binding), and X (including BCL6-co-repressor). These genes are categorized as control and regulatory genes for metabolic pathways involving the cell cycle (cyclin-dependent kinases), apoptosis, cytokine expression, Na+/K+ ATPase, stress responses, G-protein signal transduction, transcription factors, DNA repair as well as metal-regulatory transcription factor 1, MTF1 HGNC, chondroitin sulfate proteoglycan 5 (neuroglycan C), ATP-binding cassette, sub-family G (WHITE), cytochrome b-561 family protein, CDC-like kinase 1 (CLK1 HGNC) (protein tyrosine kinase STY), Na+/H+ exchanger regulatory factor (NHERF HGNC), potassium voltage-gated channel subfamily H member 2 (KCNH2), putative MAPK activating protein (PM20, PM21), ras homolog gene family, polymerase (DNA directed), delta regulatory subunit (50 kDa), leptin receptor involved in hematopoietin/interferon-class (D200- domain) cytokine receptor activity and thymidine kinase 2, mitochondrial TK2 HGNC and related genes. Significant alterations in these specific genes provide new directions for deeper mechanistic investigations that would lead to a better understanding of the molecular basis of mercury-induced toxicity and human diseases that may result from disturbances in the immune system.
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PMID:Microarray analysis of mercury-induced changes in gene expression in human liver carcinoma (HepG2) cells: importance in immune responses. 1682 88

Despite the extensive research on the pharmacology of L-arginine, there are only few data on its antithrombotic properties. We studied the effect of oral L-arginine administration in a model of arterial thrombosis in rabbits divided into three groups: group 1, group without intervention; group 2, control group, treated with normal diet and submitted to the thrombosis-triggering protocol; group 3, treated for 2 weeks with L-arginine (2.25%) prior the protocol. L-Arginine did not alter platelet aggregation nor coagulation parameters but reduced vascular activities of both ADPase (49.1 +/- 8.5 versus 28.9 +/- 8.3 versus 18.8 +/- 10.3 nmoles inorganic phosphate/min per mg protein; mean +/- SD; group 1 versus group 2 versus group 3, respectively; ANOVA F = 19.21; P < 0.0001) and ATPase (97.8 +/- 15.8 versus 52.1 +/- 11.6 versus 31.9 +/- 16.3 nmoles inorganic phosphate/min per mg protein; mean +/- SD; group 1 versus group 2 versus group 3, respectively; ANOVA, F = 34.65; P < 0.0001). L-Arginine did not reduce the thrombi area (17.1 mm, 9.02 and 48.07, versus 27.04 mm, 25.4 and 70.39, median, percentile 25 and 75 respectively, P = 0.079; group 2 versus group 3, respectively). In conclusion, oral L-arginine administration did not inhibit thrombosis, and, conversely, it significantly reduced the arterial wall ADPase and ATPase activities. This effect may limit its antithrombotic properties.
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PMID:Oral L-arginine administration does not inhibit thrombosis on an experimental model of arterial thrombosis: the effect on the apyrasic activity of the arterial wall. 1690 46

We have previously reported that male and female offspring of Sprague-Dawley rats fed a diet rich (approximately 50% of caloric intake from fat) in animal fat (lard) during pregnancy and suckling (OHF) demonstrate cardiovascular dysfunction, including blunted endothelium-dependent vasodilatation in the aorta as well as reduced renal Na(+),K(+)-ATPase activity. Cardiovascular dysfunction has been reported in other models of developmental programming and some researchers describe transmission from F(1) to F(2) generations. Here we report a study of vascular function, as assessed in isolated rings of aorta mounted in an organ bath, and renal Na(+),K(+)-ATPase activity in 6-month-old male and female F(2) offspring of lard-fed and control-fed (OC) dams (n = 13 per diet group). An increase in brain (OC 0.61 +/- 0.01% versus OHF 0.66 +/- 0.02% of bodyweight) and kidney weights (OC 0.32 +/- 0.01% versus OHF 0.37 +/- 0.01% of bodyweight) was observed in female F(2) offspring of lard-fed dams compared with F(2) controls (P < 0.03). Constrictor responses to phenylephrine in the aorta were not different from F(2) controls (repeated measures ANOVA, P = 0.85). Also, endothelium-dependent dilator function, as assessed by responses to acetylcholine (repeated measures ANOVA, P = 0.96) and passive distensibility in the absence of extracellular calcium (repeated measures ANOVA, P = 0.68), was similar. Additionally, renal Na(+),K(+)-ATPase activity was not statistically different from that observed in control animals (ANOVA, P = 0.89). Although a maternal diet rich in animal fat has deleterious effects on parameters of cardiovascular risk in F(1) animals, it does not appear that disorders previously reported in the F(1) generation are transmitted to the F(2) generation.
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PMID:Programmed aortic dysfunction and reduced Na+,K+-ATPase activity present in first generation offspring of lard-fed rats does not persist to the second generation. 1725 73


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