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

---

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

The temporal pattern of changes in the specific activities of retinal Na+, K(+)-ATPase (Na, K-ATPase) and Mg(2+)-ATPase (Mg-ATPase) were determined at several time intervals following the onset of diabetes in streptozotocin-induced diabetic (STZ: at 1, 2, 4 and 6 months) Long-Evans hooded rats, spontaneously diabetic Zucker diabetic fatty (ZDF: at 1, 2 and 4 months) rats and their age-matched controls. These animals were utilized as models for insulin-dependent diabetes mellitus (IDDM) and non-insulin-dependent diabetes mellitus (NIDDM), respectively. Na, K-ATPase specific activity, using 10(3) M ouabain, was decreased (-6% to -14%) at all time points after the appearance of hyperglycemia in the ZDF rat, but was reduced only after 4 and 6 months in the STZ rat (-8% and -14%, respectively). In contrast, Mg-ATPase activity was significantly increased (13%) after 4 months in the ZDF rat and after 6 months in the STZ rat (8%). The concentration-dependent inhibitory effects of ouabain (10(-9) to 10(-3) M) on the activity of Na, K-ATPase in diabetic rats and age-matched controls was used to assess the time-dependent effects of diabetes on the alpha 3-high ouabain affinity or the alpha 1-low ouabain affinity retinal Na, K-ATPase isozymes. The retinal Na, K-ATPase activity for the alpha 3 isozyme was significantly lower at all times examined for the ZDF (-5% to -26%) and STZ-induced diabetic rats (-8% to -14%). This was reflected in the markedly decreased half-maximal inhibitory concentrations (IC50) of ouabain for the alpha 3 isozyme. For example, after four months of diabetes, the mean +/- SEM IC50 values were 12 +/- 3 nM in the STZ rats and 48 +/- 6 nM in the age-matched controls and 19 +/- 3 nM in the ZDF rats and 30 +/- 4 nM in the age-matched controls. In contrast, the activity of the alpha 1 isozyme was slightly, but significantly, decreased at 2 and 4 months in the ZDF rats (-4% to -7%) and after 4 and 6 months in the STZ-induced diabetic rats (-3% to -9%) while the IC50 values were unchanged. Moreover, the Hill coefficient for the alpha 3 isozyme was decreased in both diabetic groups while it was unchanged for the alpha 1 isozyme.(ABSTRACT TRUNCATED AT 400 WORDS)
...
PMID:Alterations in retinal Na+, K(+)-ATPase in diabetes: streptozotocin-induced and Zucker diabetic fatty rats. 813 34

Calcium is actively transported into intracellular organelles and out of the cytoplasm by Ca2+/Mg(2+)-ATPases located in the endoplasmic reticulum and plasma membranes. We studied the effects of aluminum on calcium transport in the adult rat brain. We examined 45Ca-uptake in microsomes and Ca(2+)-ATPase activity in microsomes and synaptosomes isolated from the frontal cortex and cerebellum of adult male Long-Evans rats. ATP-dependent 45Ca-uptake was similar in microsomes from both brain regions. The addition of 50-800 microM AlCl3 resulted in a concentration-dependent inhibition of 45Ca-uptake. Mg(2+)-dependent Ca(2+)-ATPase activity was significantly lower in synaptosomes compared to microsomes in both frontal cortex and cerebellum. In contrast to the uptake studies, AlCl3 stimulated Mg(2+)-dependent Ca(2+)-ATPase activity in both microsomes and synaptosomes from both brain regions. To determine the relationship between aluminum and Mg2+, we measured ATPase activity in the presence of increasing concentrations of Mg2+ or AlCl3. Maximal ATPase activity was obtained between 3 and 6 mM Mg2+. When we substituted AlCl3 for Mg2+, ATPase activity was also stimulated in a concentration-dependent manner, but to a greater extent than with Mg2+. One interpretation of these data is that aluminum acts at multiple sites to displace both Mg2+ and Ca2+, increasing the activity of the Ca(2+)-ATPase, but disrupting transport of calcium.
...
PMID:Aluminum alters calcium transport in plasma membrane and endoplasmic reticulum from rat brain. 815 28

This investigation examined the relationship between alteration of Ca(2+)-transport systems and cytotoxicity in vitro for a number of neuroactive chemicals including environmental pollutants. 45Ca2+ uptake as a measure of Ca2+ sequestration was determined in mitochondria and microsomes isolated from cerebella of adult male Long-Evans hooded rats by differential centrifugation. Ca2+ extrusion, measured as Ca(2+)-ATPase activity, was determined in synaptosomes prepared by sucrose density gradient. Cytotoxicity (lactate dehydrogenase leakage) was assessed in primary cultures of cerebellar granule cells from 6- to 8-day-old Long-Evans rats. N-Methyl-D-aspartic acid (NMDA) did not alter synaptosomal Ca(2+)-ATPase activity or 45Ca2+ uptake in mitochondria and microsomes. However, chlorpromazine (CPZ), aluminum (Al), permethrin (PER), and deltamethrin (DEL) inhibited Ca2+ sequestration by mitochondria and microsomes. The IC50 values (microM) for CPZ, Al, PER, and DEL were 67.8, 671, 4.2, and 91.2 for mitochondrial 45Ca2+ uptake, and 129.9, 1384, > 50, and > 200 for microsomal 45Ca2+ uptake, respectively. CPZ, PER, and DEL also inhibited synaptosomal Ca(2+)-ATPase activity in a concentration-dependent manner with IC50 values of 62.5, > 400, and 246.9 microM, indicating an effect on the Ca(2+)-extrusion process. Al increased Ca(2+)-ATPase activity (EC50 = 833 microM). Although NMDA did not inhibit Ca(2+)-transport systems, it was cytotoxic at 250 microM and higher concentrations after 2 hr of exposure. Similarly, CPZ was cytotoxic at concentrations of 25 and 10 microM after 4 hr exposure. However, PER, DEL, and Al were not cytotoxic at any concentration up to 500 microM. Of all the chemicals tested, CPZ was the most potent in inhibiting Ca(2+)-transporting systems and was also cytotoxic.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Effects of selected neuroactive chemicals on calcium transporting systems in rat cerebellum and on survival of cerebellar granule cells. 825 84

We studied the effect of chronic exposure (6 weeks and 6 months) of mice to drinking (tap) water containing 1.76% (0.06 M) aluminum lactate on some cytochemical properties of the blood-brain barrier (BBB). The plasmalemma-bound enzymatic activities of alkaline phosphatase (AP) and Ca(2+)-activated adenosine triphosphatase (Ca(2+)-ATPase) were studied at the ultrastructural level. Anionic sites were localized with cationized ferritin in a pre-embedding procedure and with cationic colloidal gold in a post-embedding procedure applied to brain samples embedded in Lowicryl K4M. Intravenously injected Evans blue and horseradish peroxidase (HRP) were used for evaluation of the functional state of the BBB. The results indicate that chronic exposure to aluminum does not noticeably affect barrier function of the endothelium of cerebral cortex blood microvessels. Focal leakage of larger than capillary microvessels (presumably arterioles and venules) was observed only in a few areas, such as the basal ganglia and amygdaloid nuclei. The localization of both enzymatic activities (AP and Ca(2+)-ATPase) in microvessels remained essentially unchanged. The localization of anionic sites was also unchanged except on the luminal surface of the endothelium of a few blood microvessels located in areas of the brain where leakage of the injected HRP was noted. In these vessels the injected HRP was often attached to the luminal surface of the endothelial cells, suggesting its increased stickiness. These data, compared with our previous observations on brain microvascular endothelial cells growing in vitro, indicate that cytotoxicity of aluminum is evidently less pronounced in the living organism, presumably due to action of detoxicating and regulatory mechanisms.
...
PMID:Ultracytochemical studies of the effects of aluminum on the blood-brain barrier of mice. 828 66

Recent studies resulted in the cloning of the genes responsible for Menkes syndrome and Wilson disease. Despite the distinct clinical phenotypes of these disorders, each gene encodes a highly homologous member of the cation-transport P-type ATPase family. The remarkable evolutionary conservation of these proteins in bacteria, yeast, plants, and mammals reveals a fundamental protein structure essential for copper export in all life forms. Characterization of a molecular defect in the rat homologue of the Wilson ATPase in the Long-Evans Cinnamon rat identifies an animal model of Wilson disease and will permit experimental analysis of the precise role of this ATPase in copper transport, the effects of specific inherited mutations on transport function, and the cellular and molecular mechanisms of tissue injury resulting from copper accumulation. Finally, recent molecular genetic analysis of a distinct group of patients with low serum ceruloplasmin and basal ganglia symptoms identified a series of mutations in the ceruloplasmin gene. The presence of these mutations in conjunction with the clinical and pathologic findings clarifies the essential biological role of this abundant copper protein in metal metabolism and identifies aceruloplasminemia as a novel autosomal recessive disorder of iron metabolism.
...
PMID:Genetic and molecular basis for copper toxicity. 861 71

In the cochlea, hormones such as antidiuretic hormone and adrenocorticosteroid hormones are supposed to modulate the endolymph osmolality acting on the labyrinthine water permeability, on the one hand, and on the Na+, K(+)-ATPase, on the other hand. To test the hypothesis that these hormones are involved in the inner ear fluids homeostasis, the electrochemical composition of cochlear fluids was studied in control Long Evans rats, Brattleboro rats that are genetically deprived of antidiuretic hormone, and in adrenalectomized Long Evans rats. The results demonstrated that: i) in Brattleboro rats, the endocochlear K gradient was absent whereas the endocochlear potential and the Cl concentration gradients were maintained; the K gradient was restored by the dDAVP administration; ii) in adrenalectomized rats, no modification of the electrochemical composition of endolymph occurred; the injection of bumetanide (10 mg/kg) induced a larger decrease of the endocochlear potential in adrenalectomized rats than in control animals. These results suggest that the cellular transport systems involved in the endolymph secretion may be altered by different hormones such as antidiuretic hormone and/or adrenocorticosteroid hormones. Nevertheless, the hormonal modulation of the inner ear fluid homeostasis remains to be further documented.
...
PMID:Hormonal modulation of inner ear fluids. 872 24

This study was designed to determine if aging affects ouabain-sensitive Na(+)-pump current (Ip), an electrophysiological measure of Na,K-ATPase activity, in rat heart. Ventricular myocytes were enzymatically isolated from hearts of young adult (4-6 months of age) and aged (28-36 months of age) male Long-Evans rats. Ip was monitored using conventional whole-cell patch-clamp techniques under both maximally stimulating (85 mM intracellular Na+ with 10.8 mM extracellular K+) and 'physiological' (10 mM intracellular Na+ with 5.4 mM extracellular K+) conditions. Values were expressed relative to membrane capacitance to account for the larger cell size of the aged myocytes. Results indicated that maximal Ip is smaller (e.g. approximately 23% at the holding potential of -40 mV) in myocytes isolated from aged as compared to young adult rats. However, neither the voltage-dependence of maximal Ip nor the pump current monitored under 'physiological' conditions were affected by age in general, these data support results of previous biochemical and ion flux studies which demonstrated that aging is associated with a decline in the Na(+)-pump capacity of the myocardium.
...
PMID:Effects of aging on Na(+)-pump current in rat ventricular myocytes. 884 39

We compared the effect of GABA and the serotonin receptor agonist (+/-)-8-hydroxy-dipropylaminotetralin hydrobromide (8-OH-DPAT) on compound action potential amplitudes, latency, and conduction velocity in the spinal cord isolated from young (eight to 13-day-old) Long-Evans hooded rats. Supramaximally activated conducting action potentials and extracellular K+ activity were recorded with microelectrodes from the cuneatus-gracilis fasciculi and corticospinal tract. In the cuneatus-gracilis fasciculi, 8-OH-DPAT (10(-4) M) significantly reduced response amplitudes by 26.1 +/- 10.3% (mean +/- S.D., P < 0.0001, paired t-test, n = 27) and increased latencies by 20.3 +/- 7.9% (P < 0.0001). GABA (10(-4) M) reduced/amplitudes by 31.7 +/- 15.0% (P < 0.0001, n = 28) and increased latencies by 6.1 +/- 5.4% (P < 0.0001). However, neither GABA nor 8-OH-DPAT significantly altered conduction velocities, suggesting that the latency shifts are due to changes in activation time and not conduction velocity. In cortical spinal tract, 8-OH-DPAT (10(-4) M) depressed response amplitudes by 18.9 +/- 9.6% (P < 0.05, n = 5), increased latencies by 23.3 +/- 7.2% (P < 0.0001), but reduced conduction velocities by 19.9 +/- 10.2%. GABA (10(-4) M) reduced amplitudes by 16.4 +/- 7.5% (P < 0.01, n = 5), increased latencies by 5.3 +/- 2.3% (P < 0.05), and did not change conduction velocities. Bicuculline or picrotoxin blocked the GABA effects but did not affect the 8-OH-DPAT effects on both tracts. The potassium channel blocker tetraethylammonium did not alter the 8-OH-DPAT effects. The Na+/K(+)-ATPase inhibitor ouabain (10(-6) M) markedly enhanced the depressive GABA effects from 27.9 +/- 12.0% to 49.4 +/- 24.5% (P < 0.01, n = 9), but had no effect on 8-OH-DPAT-mediated effects. These results suggest that GABA and serotonin agonists depress axonal excitability through different and independent mechanisms.
...
PMID:Independent depressive mechanisms of GABA and (+/-)-8-hydroxy-dipropylaminotetralin hydrobromide on young rat spinal axons. 895 85

We examined the cholecystokinin (CCK)-B/gastrin receptor, H+/K+-ATPase and somatostatin gene expression, the histology and immunohistochemistry of gastrin and somatostatin of the stomach, plasma gastrin levels, and gastric acid secretion in naturally occurring CCK-A receptor gene knockout (Otsuka Long-Evans Tokushima fatty, OLETF) rats. The CCK-B/ gastrin receptor, H+/K+-ATPase and somatostatin mRNAs were determined by Northern transfer analysis. The gastric acid secretion and the plasma gastrin level were measured in vivo. The levels of CCK-B/gastrin receptor mRNA in the forestomach and the glandular stomach in OLETF rats were 2-fold higher than those of control rats, although those of H+/ K+-ATPase and somatostatin mRNAs were not different. Histological examination revealed thickening of the fundic mucosa, and hyperplasia and hypertrophy of parietal cells, although immunohistochemistry of gastrin and somatostatin revealed no significant difference from the control rats. Gastric acid secretion stimulated by gastrin or histamine was enhanced, whereas the fasting plasma gastrin level was not significantly different from that in control rats. The overexpression of CCK-B/gastrin receptor mRNA and the hyperfunction of parietal cells were observed in rats without CCK-A receptor gene expression.
...
PMID:Overexpression of cholecystokinin-B/gastrin receptor gene in the stomach of naturally occurring cholecystokinin-A receptor gene knockout rats. 946 95

Carbamoyl-phosphate synthetase consists of an amidotransferase domain or subunit (GLN) that hydrolyzes glutamine and transfers the ammonia to the synthetase component (CPS) where the biosynthetic reaction occurs. The CPS domain is composed of two homologous subdomains, CPS.A and CPS.B, that catalyze different ATP-dependent reactions involved in carbamoyl phosphate synthesis. When the individual CPS.A and CPS.B subdomains were individually cloned and expressed in Escherichia coli (Guy, H. I., and Evans, D. R. (1996) J. Biol. Chem. 271, 13762-13769), they were found to be functionally equivalent and could each independently catalyze carbamoyl phosphate synthesis. The proposal was advanced that, although the monomers could catalyze the individual partial reactions, overall synthesis of carbamoyl phosphate required a homodimer of CPS.A or CPS.B. To test this hypothesis, the GLN-CPS.B dimer was reversibly dissociated at 1500 bar in a high pressure cell. Dissociation was accompanied by a loss of both glutamine- and ammonia-dependent CPSase activity. Activity was recovered once the protein was returned to atmospheric pressure. If the sample was cross-linked before exposure to high pressure, there was no dissociation and no loss of biosynthetic activity. In contrast, the bicarbonate-dependent ATPase and the carbamoyl phosphate-dependent ATP synthetase activities were largely unaffected by pressure-induced dissociation. These experiments confirmed the hypothesis that the synthesis of carbamoyl phosphate requires the concerted action of the two active sites within the homodimer.
...
PMID:Pressure-induced dissociation of carbamoyl-phosphate synthetase domains. The catalytically active form is dimeric. 960 18


<< Previous 1 2 3 4 5 6 Next >>

---