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)

Cell activation of different cell types is accompanied by receptor-mediated stimulation of phospholipase C and a consequent breakdown of phosphatidylinositol 4,5-bisphosphate. Evidence suggests that GTP-binding proteins are involved in this signal transduction mechanism, which couples receptors to phospholipase C. Both the hydrolysis products diacylglycerol (DG) and inositol 1,4,5-trisphosphate (IP3) are intracellular messengers for cellular responses such as secretion, as illustrated by the pancreatic acinar cell. IP3 releases Ca2+ from a nonmitochondrial Ca2+ pool likely to be the endoplasmic reticulum (ER). This Ca2+ release leads to a transient rise in the cytosolic free Ca2+ concentration from approximately 100 to approximately 800 nmol/liter, by which enzyme secretion is initiated. For sustained secretion, Ca2+ influx into the cell is necessary to keep the cytosolic free Ca2+ concentration at a slightly elevated level. Activation of protein kinase C by DG and Ca2+ seems to play a major role in the second, sustained phase of secretion. Ca2+ reuptake into the ER and Ca2+ extrusion from the cell are achieved by (Ca2+ + Mg2+)-ATPase in both the ER and the plasma membrane as well as by an Na+/Ca2+ exchange in the latter. In the final step of exocytosis, protein phosphorylation by Ca2+-, DG-, and cAMP-dependent protein kinases is probably involved.
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PMID:The role of phosphatidylinositides in stimulus-secretion coupling in the exocrine pancreas. 314 61

The behaviour of Ca2+ ATPase activity in relation to Ca2+ transport process was studied under different experimental conditions in canine cardiac microsomal fraction predominantly containing sarcoplasmic reticulum. The total Ca2+ concentration required for half maximal activation (Ka) of microsomal Ca2+ ATPase and Ca2+ uptake did not differ significantly, unless 0.1 mmol/l EGTA was present in the incubation media. Pretreatment of cardiac microsomes with membrane disruptive agents like phospholipase A, trypsin as well as deoxycholate strongly increased (2-3 fold) Ca2+ ATPase activity but uptake rate of Ca2+ declined. Only in phospholipase C and beta-glucuronidase pretreatment, a parallel decrease of Ca2+ ATPase and uptake was observed. In presence of excess (free)Ca2+ (greater than 10 mumol/l) both Ca2+ ATPase as well as Ca2+ uptake were inhibited, however, Ca2+ binding process remained unaltered. Likewise, low pH completely altered the relation between Ca2+ binding and ATPase activity; whereas Ca2+ ATPase was inhibited, Ca2+ binding did not change. Our present data provide evidence for some cellular factors that may be involved in producing uncoupling of microsomal Ca2+ ATPase from Ca2+ accumulation process that was previously observed in various pathological situations.
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PMID:Behaviour of cardiac microsomal Ca2+ pump under conditions that may simulate pathological situations. 316 76

Daily subcutaneous injection of gentamicin (100 mg/kg) for 2 days produced a significant decrease in the activities of alkaline phosphatase, a brush-border membrane marker, and Na+-K+ ATPase, a basolateral membrane marker, in adult rat kidney cortex. Analysis of homogenate and lysosomal fractions revealed a significant rise in the concentration of total renal cortical phospholipid, phosphatidylserine, phosphatidylcholine, and phosphatidylinositol. In the lysosomal fraction, an increase in the levels of phosphatidylglycerol and phosphatidylethanolamine was also noted. Daily, oral chlorphentermine (60 mg/kg) administration for 5 days significantly reduced renal Na+-K+ ATPase without a marked change in alkaline phosphatase. As in the case of gentamicin, chlorphentermine produced a significant elevation in phosphatidylserine, phosphatidylcholine, and phosphatidylinositol as well as total phospholipid in both the homogenate and lysosomal fractions of kidney cortex. The observed chlorphentermine- or gentamicin-induced renal phospholipidosis was associated with a significant reduction in the activity of phosphatidylinositol-specific phospholipase C. The drug-induced inhibition of phospholipase C was quantitatively equal in the renal cortical homogenate and lysosomal fractions. In addition, gentamicin significantly inhibited the activity of phosphatidylserine-phospholipase C and phosphatidylcholine-phospholipase C in renal cortical homogenate. In contrast, only the activity of phosphatidylinositol-specific phospholipase C was decreased in chlorphentermine-treated kidneys. Evidence thus indicates that the gentamicin-induced accumulation of phospholipid in renal cortical lysosomes is associated with inhibition of various forms of phospholipase C, while in the case of chlorphentermine the inhibition of different phospholipases may be involved in phospholipid accumulation.
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PMID:Cationic amphiphilic drug-induced renal cortical lysosomal phospholipidosis: an in vivo comparative study with gentamicin and chlorphentermine. 342 75

Previous work has demonstrated that myocardial ischemia results in a breakdown of the excitation-contraction coupling system of cardiac muscle associated with lysosomal activation. It has been hypothesized that lysosomal activation during the course of myocardial ischemia is mediated by the production of oxygen free radicals. We have tested the hypothesis that myocardial ischemia results in the activation of lysosomal phospholipase C and disruption of calcium transport in sarcoplasmic reticulum (SR) mediated by oxygen free radicals. Three groups of dogs were studied: sham-operated controls (n = 6); normothermic global ischemia of 30-min duration (n = 6); and 30 min of normothermic global ischemia pretreated with intracoronary superoxide dismutase (SOD, 10 micrograms/ml) plus catalase (25 micrograms/ml). In vitro, isolated SR demonstrated a significant depression of calcium uptake rates and Ca2+-stimulated, Mg2+-dependent ATPase activity at both pH 7.0 and 6.4 with the depression at pH 6.4 greater than 7.0. This depression of SR function was significantly inhibited in hearts pretreated with SOD plus catalase. In sham-operated controls, acid-induced dysfunction was associated with substantial loss of phospholipid phosphorus and major changes in phospholipid composition. SR contained an extremely active, ion-independent sphingomyelinase-phospholipase C (SM-PLC) that had maximal activity at pH 4.5-5.0. This SM-PLC was activated when control SR was incubated at acid pH and the specific activity of SM-PLC was decreased 50% in SR isolated from normothermic global ischemia. Activity remained at control levels in hearts pretreated with SOD plus catalase.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Sarcoplasmic reticulum dysfunction: phospholipid alterations induced by lysosomal phospholipase C. 377 91

The role of lipids of the sarcotubular membranes in their Ca(++) uptake and Mg-ATPase activities was investigated. Treatment of the membranes with phospholipase C inhibits both processes. Treatment with phospholipase A and phospholipase D, which results in massive hydrolysis of the sarcotubular phospholipids, does not inhibit either the Ca(++) uptake or the Mg-ATPase activities, nor does treatment with the polyene antibiotics affect these processes. Essential fatty acid deficiency alters sarcotubular membrane lipids; they contain much less stearic, linoleic, and arachidonic acids and much more oleic and eicosatrienoic acids than normally, but do not lose the ability to actively sequester Ca(++). It is concluded that neither nonpolar lipids nor the nonpolar regions of polar lipids are involved in Ca(++) sequestering and Mg-ATPase activities of the sarcotubular membranes. Of the polar components, the phosphoryl moiety of the phospholipids is required for both activities. However, the phosphoryl group appears to be required for the maintenance of the membranous structure necessary for Ca(++) sequestration rather than serving specifically in the active transport process. That treatment with phospholipase D, which results in the conversion of much of the sarcotubular phospholipid from a dipolar to an anionic structure, does not affect Ca(++) uptake activity is a most remarkable finding.
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PMID:Relation of lipid structure of sarcotubular vesicles to Ca++ transport activity. 423 45

Colloidal iron staining, calcium binding and enzyme activities were studied in the isolated rat heart sarcolemma. Colloidal iron staining of the sarcolemma revealed a high density of negatively charged sites associated with the cell surface. This membrane fraction was found to have calcium binding activity at both low (0.1 mM) and high (1.25 mM) concentrations of calcium. Pretreatment of the sarcolemma with either trypsin, phospholipase C or neuraminidase, was associated with a reduction in colloidal iron staining as well as decreased calcium-binding activity at high concentrations of calcium. Calcium binding at low concentrations was decreased by both trypsin and neuraminidase. Mg2+ ATPase, Ca2+ ATPase, and Na+-K+ ATPase activities were altered by neuraminidase and trypsin treatments, whereas phospholipase C treatment altered Na+-K+ ATPase only. It is concluded that both surface negative charge and calcium-binding sites associated with the isolated rat heart sarcolemma are contributed by a mosaic of biomolecules including proteins, phospholipids and glycoproteins, and alterations in the surface charge may influence the activities of membrane-bound enzymes.
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PMID:Negatively charged sites and calcium binding in the isolated rat heart sarcolemma. 616 50

ATPase activity and Ca2+ uptake were examined in microsomal membrane fractions isolated from guinea pig stomach smooth muscle which had been exposed to phospholipase C (PLC). Basal Mg2+-ATPase, Na+, K+-ATPase and Ca2+, Mg2+-ATP activities were inhibited in a time dependent manner by PLC treatment. There was positive correlations between each of these ATPase activities and total phospholipid content of the microsomal fraction. Phosphotidylcholine restored Ca2+, Mg2+-ATPase activity of the microsomal fraction isolated from the tissue which had been treated with PLC for 30 min but not after 60 min. Ca2+ uptake in the presence of ATP by microsomal fraction from tissue treated with PLC for 60 min was significantly decreased. The results provide a cellular basis for the inhibitory effect of PLC on contractility of stomach smooth muscle.
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PMID:ATPase activity and calcium uptake of microsomes isolated from stomach smooth muscle after exposure to phospholipase C. 622 98

Sarcolemma-rich microsomal fractions were isolated from rabbit ventricular muscle by differential centrifugation and discontinuous sucrose gradient techniques. The fractions were characterized in terms of calcium binding, enzymic activity, gel electrophoresis, and ultrastructure. Racemate verapamil (1 microM) reduced (P less than 0.001) the Ca2+-binding and Ca2+-activated ATPase activity of these fractions; the activity resided in the l-isomer. 14C-Labeled verapamil was found to be bound to carbohydrate residues in the membrane. Pretreatment with trypsin or phospholipase C diminished the 14C-verapamil binding. When added to isolated hearts perfused under conditions of "low flow," verapamil prevented mitochondrial Ca2+ overload.
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PMID:Cardiovascular receptors and calcium. 624 88

1. Extensive treatment of rabbit kidney microsomes with phosphatidylinositol-specific phospholipase C under various conditions never resulted in more than 75% hydrolysis of the substrate. 2. The non-degraded fraction of the phosphatidylinositol (10-12 nmol per mg microsomal protein) could be recovered only by an acidic extraction procedure. 3. The (Na+ + K+)-ATPase activity found in those membranes was not affected by this treatment. 4. Complete degradation of phosphatidylinositol could be easily achieved when the phospholipase was applied to rat liver microsomes which do not contain any detectable (Na+ + K+)-ATPase activity. 5. It is concluded that in rabbit kidney microsomes a close association exists between the (Na+ + K+)-ATPase and that fraction of the phosphatidylinositol that is directly involved in the maintenance of its activity.
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PMID:The fraction of phosphatidylinositol that activates the (Na+ + K+)-ATPase in rabbit kidney microsomes is clearly associated with the enzyme protein. 627 Dec 11

(1) The total phospholipid content of a gradient purified (K+ + H+)-ATPase preparation from pig gastric mucosa is 105 mumol per 100 mg protein, and consists of 29% sphingomyelin, 29% phosphatidylcholine, 28% phosphatidylethanolamine, 10% phosphatidylserine and 4% phosphatidylinositol. The cholesterol content corresponds to 50 mumol per 100 mg protein. (2) Treatment with phospholipase C (from Clostridium welchii and Bacillus cereus) results in an immediate decrease of the phosphate content. Up to 50% of the phospholipids are hydrolyzed by each phospholipase C preparation alone, without further hydrolysis by increased phospholipase concentration or prolonged incubation time. Combined treatment with the two phospholipase C preparations, sequentially or simultaneously, hydrolyzes up to 65% of the phospholipids. (3) The (K+ + H+)-ATPase and K+ stimulated p-nitrophenylphosphatase activities are decreased proportionally with the total phospholipid content, indicating that these enzyme activities are dependent on phospholipids. (4) Phospholipase C treatment does not change optimal pH, Km value for ATP and temperature dependence of the gastric (K+ + H+)-ATPase, but slightly decreases the Ka value for K+. (5) Phospholipase C treatment lowers the AdoPP[NH]P binding and phosphorylation capacities, suggesting that inactivation occurs primarily on the substrate binding level. (6) Most of the results can be understood by assuming that hydrolysis of the phospholipids by phospholipase C leads to aggregation of the membrane protein molecules and complete inactivation of the aggregated ATPase molecules.
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PMID:Studies on (K+ + H+)-ATPase. IV. Effects of phospholipase C treatment. 627 55


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