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 substructure of the cardiac myosin molecule was examined by the limited proteolytic digestion of the parent molecule with (dialdehyde starch)-methylenedianiline-mercuripapain, S-MDA-mercuripapain, at low temperatures and neutral pH, using moderate enzyme to myosin rations. Pertinent properties of the insoluble enzyme complex were also examined. Kinetic, ultracentrifugal, and chromatographic observations of the fragmentation process revealed that a single type of lytic reaction occurs during the early stages, predominately releasing heavy meromyosin subfragment 1 (HMM-S1) and myosin rods. With further time digestion, the rods are additionally cleaved yielding light meromyosin and HMM-S2, and HMM-S1 is found to be partially degraded. The major proteolytic subfragments were isolated, purified, and characterized with respect to their enzymatic, optical, amino acid, and physicochemical properties. Only HMM-S1 exhibited Ca-2+-activated ATPase activity, and at a level three- to fourfold higher than that of native myosin. Moreover, its hydrohynamic properties suggest that it is globular in structure. On the other hand, light meromyosin-A (LMM-A) (which consists mainly of rods), and HMM-S2 appear to be highly asymmetric, rigid, alpha-helical molecules devoid of the amino acid proline. Strong similarities were evident in all aspects upon comparison of these results with documented information concerning the skeletal system. On the basis of the physical and chemical properties of the proteolytic subfragments relative to that of native myosin, it was further concluded that the cardiac myosin molecule is a double-stranded, alpha-helical rod ending in tow subfragment 1 globules, of which only one may be enzymatically active at a time.
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PMID:Rabbit cardiac myosin. II. Proteolytic fragmentation with insolubilized papain. 23 79

Suspensions of renal proximal tubules (RPT) are the in vitro model for many biochemical and physiologic investigations. Inasmuch as there are numerous procedures for tubule isolation and the more commonly used enzymatic procedures may disrupt the basement membrane, there is a need for information comparing the influence of various isolation methods on RPT viability and function in long-term suspension. Rabbit RPT isolated a) enzymatically (ENZ) by in vitro collagenase digestion and Percoll size and density purification, and b) mechanically (MECH) by in vitro iron oxide perfusion and purification by sieving and magnetic removal of glomeruli were compared for viability, morphology, and functional stability during long-term suspension. RPT isolated by ENZ and MECH methods had excellent viability (less than 15% lactate dehydrogenase release), limited lipid peroxidation (less than 0.2 nmol MDA.mg protein-1), and stable nystatin-stimulated oxygen consumption (QO2) (38 and 36 nmol O2.mg protein-1.min-1) throughout 24 h of incubation. Basal QO2 was higher in ENZ than MECH tubules (27 and 19 nmol O2.mg protein-1.min-1, respectively), and was unchanged over 24 h in each preparation. The higher basal QO2 in ENZ tubules was ouabain-sensitive, suggesting an increased rate of Na+,K(+)-ATPase activity in these tubules. Total glutathione content (oxidized + reduced) in ENZ and MECH tubules increased over the 24-h incubation from 8 to 18 nmol.mg protein-1. gamma-Glutamyltranspeptidase (GGT) activity of the RPT homogenates was equivalent in both preparations and stable over time. The ratio of suspension GGT activity to homogenate GGT activity doubled (0.4 to 0.8) during the incubation period. MECH tubules retained their tubule structure during 24 h of incubation whereas the ENZ tubules had a striking loss of tubular morphology over time. These results show that ENZ- and MECH-isolated renal proximal tubule suspensions exhibit similar biochemical properties in long-term incubations but differ in ouabain-sensitive QO2 and the retention of tubular morphology. The loss of tubular morphology and the increase in the rate of Na+,K(+)-ATPase activity in ENZ tubules may be secondary to the disruption of the tubular basement membrane.
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PMID:Differences in enzymatic and mechanical isolated rabbit renal proximal tubules: comparison in long-term incubation. 197 32

The purpose of this study was to investigate the dynamic changes of the level of lipid peroxidation products (malonaldehyde, MDA) of intestine, intestinal water, Na-K ATPase activity of intestinal mucosa and the intestinal leucine absorption rate of rats subjected to 30% III degrees burns. The results showed that the value of the intestinal MDA was higher, the Na-K ATPase activity of the intestinal mucosa reduced markedly, the wet/dry ratio of intestinal weight was increased significantly and the intestinal leucine absorption rate in vivo was distinctly reduced postburn. However, the content of intestinal MDA and the wet/dry ratio of intestine weight was significantly reduced, and the Na-K ATPase activity and leucine absorption rate was increased in burn rats treated with SOD and CAT than in untreated burn rats. These results strongly suggested that lipid peroxide may play an important role in the impairment of leucine absorption rate of intestine after burns, and the edema and reduced Na-K ATPase activity of intestinal mucosa resulted from the increased lipid peroxide might take active parts impairing the intestinal absorption.
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PMID:[Peroxidation of the small intestine and its effect on absorption of amino acids in burned rats]. 216 26

Mitochondrial ATPase and adenylate kinase activity of hepatoma cells were inhibited by hematoporphyrin derivative (HPD) followed by photoirradiation. Inhibition of ATPase activity was a dose- and time-related event. Malonaldehyde (MDA) content of mitochondrial membranes was markedly increased by HPD plus light. The content of mouse liver microsomal cytochrome P-450 was greatly increased after intraperitoneal injection of HPD for 4 days (5 mg/kg/day). The liver weight, and levels of liver microsomal G-6-phosphatase, MDA and triglyceride (TG) showed no difference in treated vs. control animals. The data presented here demonstrate that mitochondria may be a sensitive site of action of HPD photosensitization, and inactivation of ATPase and adenylate kinase may be an important contributing factor to tumor cell damage and death.
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PMID:Photosensitization of mitochondrial adenosine-triphosphatase and adenylate kinase by hematoporphyrin derivative in vitro. 300 50

We examined the role of reactive oxygen metabolites and the protective effect of zinc-induced metallothionein (MT) synthesis on gentamicin nephrotoxicity both in vivo and in vitro. In vivo study we found that the MT content of renal cortex of the zinc preinjected rats was significantly increased, and proximal tubular necrosis and acute renal failure caused by injection of gentamicin were ameliorated. In suspended proximal tubules (PT), Na(+)-K(+)-ATPase activity and DNA synthesis were suppressed by the addition of gentamicin, but in zinc-pretreated rats' PT, these were not suppressed by the addition of gentamicin. Meanwhile MDA and hydroxyl radicals were significantly less in zinc-pretreated rats' PT compared to that in the control. Finally, we found that gentamicin enhanced superoxide anion and hydroxyl radical productin in renal cortical mitochondria. Superoxide anion could be suppressed by SOD and hydroxyl radical could be scavenged by DMSO, DFO and CAT. Our data confirm that hydroxyl radicals play a role in the pathogenesis of gentamicin nephrotoxicity, gentamicin can induce suppression of Na(+)-K(+)-ATPase activity and DNA synthesis in rats' proximal tubules leading to renal injury; this injury may be relevant to reactive oxygen metabolites generated by gentamicin. Renal cortical mitochondria is the source of reactive oxygen metabolites, which induces renal injury, and zinc-induced metallothionein synthesis could ameliorate gentamicin nephrotoxicity via scavenging reactive oxygen metabolites.
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PMID:Mechanism of gentamicin nephrotoxicity in rats and the protective effect of zinc-induced metallothionein synthesis. 780 Feb 47

Human metastatic breast cancer cells in culture contain large acidic vesicles (diameter 5-10 microns) in which endocytosed extracellular matrix can be digested by activated lysosomal proteinases such as cathepsin D (P. Montcourrier et al. (1990). Cancer Res. 50, 6045-6054). We examined these large compartments by transmission electron microscopy, measured their pH by video-enhanced epifluorescence using FITC-dextran, and studied their functional significance. Their presence in metastatic MDA-MB231 cells was found to be correlated with an increased ability of cells to migrate through Matrigel and a high cathepsin D concentration. These cells were able to phagocytose 1.24 microns diameter latex beads and fluorescence Matrigel and incorporate this extracellular material into large acidic vesicles. This indicated that large acidic vesicles were associated with both phagocytosis and invasion, and are heterophagolysosomes rather than autophagosomes. Large acidic vesicles were actively acidified with a H(+)-ATPase vacuolar pump specifically inhibited by bafilomycin A1, and reached pH values (< 4), lower than the lysosomal value (pH approximately 5) in the same cells and in specialized phagocytotic cells such as macrophages. We conclude that the phagocytotic activity of breast cancer cells, associated with high cathepsin D expression, and high acidification potential, characterize cancer cells that have migrated through Matrigel.
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PMID:Characterization of very acidic phagosomes in breast cancer cells and their association with invasion. 784 58

To understand the mechanism of action of the antitumor arotinoid mofarotene (Ro 40-8757), differential screening of cDNA libraries with cDNA probes prepared from treated or untreated breast-cancer cells was performed. Several genes were identified that appeared to be regulated by mofarotene, including a mitochondrial gene encoding a subunit of NADH dehydrogenase (NDI). This gene was down-regulated in the breast-cancer cell line MDA-MB-231 after treatment with the arotinoid for 3 to 6 hr. Down-regulation of NDI was detected in 2 other breast-carcinoma cell lines (ZR-75-I and MCF-7) and a pancreatic cancer cell line (BxPC3), but not in the normal fibroblast cell line Wi-38 or several other tumor cell lines. This effect was blocked by addition of cycloheximide to the medium. The retinoids, all-trans and 9-cis retinoic acids, did not affect the expression of NDI in MDA-MB-231 cells, demonstrating that mofarotene was not acting through the nuclear retinoic-acid receptors. In the estrogen-receptor-expressing breast-cancer line ZR-75-I, tamoxifen had no effect on NDI expression. The cytotoxic drugs doxorubicin, 5-FU and vincristine also had no effect on regulation of this gene. Two mitochondrial proteins encoded in the nucleus, ATPase beta subunit and mitochondrial transcription factor I, were not down-regulated by mofarotene. Addition of mofarotene to cells incubated in glucose-free medium led to their death. These results indicate that down-regulation of mitochondrial gene transcription is specific to mofarotene and may explain, in part, the anti-proliferative effects of this compound.
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PMID:Down-regulation of mitochondrial gene expression by the anti-tumor arotinoid mofarotene (Ro 40-8757). 792 84

In the model of transient brain ischemia of 6-min duration in gerbils we have estimated: 1. The concentration of brain gangliosides: A significant decrease to about 70% of control was observed selectively in the hippocampus at 3 and 7 d after ischemia. 2. The activity of Na+,K(+)-ATPase: The enzyme activity was not affected in either hippocampus nor in cerebral cortex. 3. The malonaldehyde (MDA) concentration: The levels of MDA had increased at 30 min after ischemia up to 123 and 129% of control in hippocampus and cerebral cortex, respectively. 4. Immunoreactivity of protein kinase C detected by Western blotting: In hippocampus the early translocation toward membranes was followed by a decrease in total enzyme content at 6, 24, 72, and 96 h of postischemic recovery. Also, a sharp increase of 50 kDa isoform (PKM) was noticed immediately and at the early recovery times. The behavior of these biochemical markers of ischemic brain injury in the hippocampus after the short (6 min) insult was contrasted with their reaction in the cerebral cortex as well as after prolongation of the ischemia to 15 min. These results taken together indicate that an early increase in PKC translocation followed by a decrease is the most symptomatic for selective, delayed, postischemic hippocampal injury, resulting from short duration (6 min) ischemia of the gerbil brain.
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PMID:Protein kinase C as an early and sensitive marker of ischemia-induced progressive neuronal damage in gerbil hippocampus. 829 17

The myocardial ATPase activity and Ca2+ content were investigated in rats with full thickness skin burn injury of 30% TBSA. The results showed that there were significant inhibitions of Na+, K(+)-ATPase,Ca2+, Mg(2+)-ATPase, and Ca(2+)-ATPase activities of myocardium after burn injury. The burn injury could result in increase of calcium content in myocardium. Burned rats also had a higher level of MDA in heart tissue when compared to controls. This study demonstrates that the membrane defects with respect to ATPase activity, oxygen free radical, and Ca2+ overload in myocardium may be associated with damage of myocardium after burns.
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PMID:[Changes in myocardial ATPase activity and Ca2+ content in burned rats]. 856 26

The aim of this experiment is to study the mechanism of APN in alleviating the Ca(2+)-overloading in dog model during the process of ischemic reperfusion. In comparison with the sustained ischemic group, the parameters in the ischemic reperfusion group demonstrated: Ca(2+) of ischemic region of myocardial cell increased (P < 0.05), Na+ increased remarkably (P < 0.01), the activity of Ca(2+)-ATPase dropped remarkably (P < 0.01), and MDA increased significantly (P < 0.01). Whereas in the group pretreated with APN, the Ca(2+) in the relevant area reduced (P < 0.05), Na+ decreased significantly (P < 0.01), the activity of Ca(2+)-ATPase and Na+-K+ ATPase increased remarkably (P < 0.01), and MDA decreased significantly (P < 0.01). These findings indicate tha APN may improve the activity of sarcolemma ATPase in alleviating the Ca(2+) and Na+ -overloading by decreasing the harmful effect of oxygen free radicals.
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PMID:An experimental study of the mechanism of andrographis paniculata nees (APN) in alleviating the Ca(2+)-overloading in the process of myocardial ischemic reperfusion. 873 24


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