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)

Our results showed that l-stepholidine (l-SPD) inhibited basal Ca(2+)-ATPase activity in rat striatal synaptosomes with an IC50 of 31.5 mumol.L-1, suggesting its interaction with Ca2+ transport. l-SPD inhibited also calmodulin (CaM)-activated basal Ca(2+)-ATPase in a concentration-dependent manner. A complete reversal of CaM activation of Ca(2+)-ATPase was observed with l-SPD 10 mumol.L-1. The activity of synaptosomal Ca(2+)-ATPase and membrane-bound CaM level were decreased in haloperidol (1 mg.kg-1.d-1, ip) and l-SPD (5, 10, and 30 mg.kg-1.d-1, ip) treated rats for 7 and 14 d, respectively. But the activity of Ca(2+)-ATPase and membrane CaM level were increased after treatment with the same of doses haloperidol and l-SPD for 21 d. During the treatments with haloperidol and l-SPD cytosolic and nuclear CaM levels were not altered. These results suggest that l-SPD may modulate the release and synthesis of dopamine (DA) and the negative feedback regulation of presynaptic DA receptors by altering Ca2+ and CaM regulating processes in the central dopaminergic nervous system.
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PMID:Effects of l-stepholidine on synaptosomal Ca(2+)-ATPase and subcellular calmodulin in rat striatum. 145 49

Calcium ions have been proposed to serve as important regulatory elements in stimulus-response coupling for phytochrome responses. An important test of this hypothesis will be to identify specific targets of calcium action that are required for some growth or development process induced by the photoactivated form of phytochrome (Pfr). Initial studies have revealed that there are at least two enzymes in pea nuclei that are stimulated by Pfr in a Ca(2+)-dependent fashion, a calmodulin-regulated nucleoside triphosphatase and a calmodulin-independent but Ca(2+)-dependent protein kinase. The nucleoside triphosphatase appears to be associated with the nuclear envelope, while the protein kinase co-purifies with a nuclear fraction highly enriched for chromatin. This short review summarizes the latest findings on these enzymes and relates them to what is known about Pfr-regulated nuclear metabolism.
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PMID:Calcium-regulated nuclear enzymes: potential mediators of phytochrome-induced changes in nuclear metabolism? 147 26

1. The rate of energy expended for the clearance of sarcoplasmic Ca2+ by sarcoreticular Ca2+ uptake process(es), plus the concomitant metabolic reactions, was evaluated from measurements of resting heat production by mouse soleus muscle before and after indirect inhibition of Ca2+ uptake by sarcoplasmic reticulum (SR). 2. Direct inhibition of the Ca2+, Mg(2+)-ATPase of SR membrane in intact muscle preparations exposed to the specific inhibitor 2,5-di(tert-butyl-1,4-benzohydroquinone (tBuBHQ) slowly increased the rate of heat production (E). Indirect inhibition of SR Ca2+ uptake was obtained by reducing sarcoplasmic Ca2+ concentration (Ca2+i) as a consequence of reducing Ca2+ release from the SR using dantrolene sodium. This promptly decreased E by 12%. Exposure of the preparations to an Mg(2+)-enriched environment (high Mg2+) or to the chemical phosphatase 2,3-butanedione monoxime (BDM), two other procedures aimed at decreasing SR Ca2+ release, also acutely decreased E, by 20 and 24%, respectively. 3. Subthreshold-for-contracture depolarization of the sarcolemma achieved by increasing extracellular K+ concentration to 11.8 mM induced a biphasic increase of E: an initial peak to 290% of basal E, followed by a plateau phase at 140% of basal E during which resting muscle tension was increased by less than 3%. Most, if not all, of the plateau-phase metabolic response was quickly suppressed by dantrolene or high Mg2+ or BDM. Another means of increasing SR Ca2+ cycling was to partially remove the calmodulin-dependent control of SR Ca2+ release using the calmodulin inhibitor W-7. The progressive increase in E with 30 microM-W-7 was largely reduced by dantrolene or high Mg2+ or BDM. 4. In the presence of either dantrolene or BDM to prevent the effect of W-7 on SR Ca2+ release, exposure of the muscle to W-7 acutely suppressed about 3% of E. This and the above results confirm that the plasmalemmal, calmodulin-dependent Ca(2+)-ATPase, although a qualitatively essential part of the Ca2+i homeostatic system of the cell, can only be responsible for a very minor part of the energy expenditure devoted to the homeostasis of Ca2+i. Active Ca2+ uptake by SR which, at least in the submicromolar range of Ca2+i, is expected to be responsible for most of this Ca(2+)-dependent energy expenditure, might dissipate up to 25-40% of total metabolic energy in the intact mouse soleus under basal and near-basal conditions.
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PMID:Ca(2+)-dependent heat production under basal and near-basal conditions in the mouse soleus muscle. 148 67

Myosin I, an actin-dependent force-generating enzyme, has been purified from three mammalian sources: bovine adrenal medulla, adrenal cortex, and brain. The purification procedure includes extraction of tissue with ATP at low ionic strength and coprecipitation with actin, followed by gel filtration on Sepharose 4B, anion-exchange chromatography on Q Sepharose, and affinity chromatography on ATP-agarose. Mammalian myosin I molecules are composed of a heavy chain of 116 kDa and multiple low molecular weight polypeptides identified as calmodulin. The structural and enzymatic properties of adrenal medulla myosin I were further characterized. This enzyme exhibits high K+,EDTA- and Ca(2+)-ATPase specific activities (about 0.2 mumol.min-1 per mg of protein), whereas the Mg(2+)-ATPase activity is very low (1-3 nmol.min-1.mg-1). The Mg(2+)-ATPase of medulla myosin I is activated by F-actin in a Ca(2+)-dependent manner: activity is stimulated 40-fold in the presence of EGTA and 90-fold in the presence of 10 microM Ca2+. Two structural domains of the myosin I heavy chain were identified. A 74-kDa chymotryptic fragment contains the catalytic site, while a 36-kDa polypeptide contains the calmodulin-binding sites. These results indicate that mammalian myosin I is more closely related to myosin I from the avian intestinal brush border than to the enzymes isolated from the protozoans Acanthamoeba and Dictyostelium.
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PMID:Purification and characterization of a mammalian myosin I. 153 Sep 90

Recently, one of the authors (K.I.) and other investigators reported that myosin light chain (MLC) of smooth muscle (gizzard, arterial and tracheal) was diphosphorylated by myosin light chain kinase (MLCK) and that diphosphorylated myosin showed a marked increase in the actin-activated myosin ATPase activity in vitro and ex vivo. In this study, we prepared myosin, actin, tropomyosin (human platelet), MLCK (chicken gizzard) and calmodulin (bovine brain) and demonstrated diphosphorylation of MLC of platelet by MLCK in vitro. Our results are as follows. (1) Platelet MLC was diphosphorylated by a relatively high concentration (greater than 20 micrograms/ml) of MLCK in vitro. As a result of diphosphorylation, the actin-activated myosin ATPase activity was increased 3 to 4-fold as compared to the monophosphorylation. (2) Both di- and monophosphorylation reactions showed similar Ca2+, KCl, MgCl2-dependence. Maximal reaction was seen at [Ca2+] greater than 10(-6) M, 60 mM KCl and 2 mM MgCl2. This condition was physiological in activated platelets. (3) Di- and monophosphorylated myosin showed similar Ca2+, KCl-dependence of ATPase activity but distinct MgCl2-dependence. Diphosphorylated myosin showed maximal ATPase activity at 2 mM MgCl2 and monophosphorylated myosin showed a maximum at 10 mM MgCl2. (4) The addition of tropomyosin stimulated actin-activated ATPase activity in both di- and monophosphorylated myosin to the same degree. (5) ML-9, a relatively specific inhibitor of MLCK, inhibited the aggregation of human platelets induced by thrombin ex vivo in a dose-dependent manner. Moreover, this drug also partially inhibited both di- and monophosphorylation reactions and actin-activated ATPase activity. On the other hand, H-7, a synthetic inhibitor of protein kinase C, had little effect on the aggregation of human platelets induced by thrombin ex vivo. From these results, we conclude that diphosphorylation of platelet myosin by MLCK may play an important role in activated platelets in vivo.
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PMID:Diphosphorylation of platelet myosin by myosin light chain kinase. 153 1

Normal and sickle cell erythrocyte membranes were examined for significant differences in their ATPase activities, thiobarbituric acid reactive products formed (measured relative to malondialdehyde), membrane protein polymerization, and number of protein-free sulfhydryl groups when treated with 0.5 mmol/L t-butylhydroperoxide (tBHP) for 30 minutes. Isolated sickle cell membranes treated with tBHP produced significantly greater inhibition in both their basal and calmodulin-stimulated Ca2+ + Mg(2+)-ATPase activities (75% inhibition in both cases) compared with that of control membranes. In addition, there was significantly more malondialdehyde formed from sickle cell membranes compared with control membranes. Oxidation caused greater protein polymerization in sickle cell membranes compared with normal membranes as demonstrated by the formation of high molecular weight polymers separated on sodium dodecyl sulfate polyacrylamide gels. The number of free sulfhydryl groups present in spectrin and actin decreased more in sickle cell membranes as measured by 3H-N-ethyl maleimide autoradiography and gel scanning. To prevent enzyme inhibition, erythrocyte membranes were treated with tBHP in the presence of 1 mmol/L ascorbate, a potential antioxidant, and 1 mmol/L desferal, an iron chelator. Both ascorbate and desferal added alone with tBHP were effective in preventing inhibition of the basal and calmodulin-stimulated Ca2+ + Mg(2+)-ATPase activities in normal membranes, but in sickle cell membranes only the addition of ascorbate and desferal together offered significant protection. The enhanced oxidation observed with sickle cell membranes can be mimicked in normal white membranes by adding hemoglobin, hemin, or ferrous chloride in the presence of tBHP. In contrast to hemoglobin, ferrous chloride has the ability to enhance membrane oxidation in the presence of ascorbate with or without tBHP. Furthermore, the addition of desferal to these membranes greatly decreased the iron-ascorbate-tBHP oxidation of erythrocyte membranes as determined by the sustained ATPase activities and the reduced formation of malondialdehyde. Maximal protection was provided by 1 mmol/L desferal in the presence of 1 mmol/L ascorbate, although some protection was observed even at 10 mumol/L, the lowest concentration tested. These results are discussed in light of the pro- and anti-oxidant effects of ascorbate in the absence and presence of iron and tBHP.
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PMID:Increased susceptibility of the sickle cell membrane Ca2+ + Mg(2+)-ATPase to t-butylhydroperoxide: protective effects of ascorbate and desferal. 153 18

The plasma membrane Ca(2+)-pumping ATPase (Ca(2+)-ATPase) mRNAs are encoded on four different genes designated PMCA1-PMCA4. The primary transcripts from some of these genes are known to be alternately spliced in the region encoding the regulatory domains of the enzymes. The known alternately spliced forms of these Ca(2+)-ATPase mRNAs and a new spliced variant of PMCA4 (PMCA4b), presented here, represent at least nine different mRNAs encoding the Ca(2+)-ATPases. In this report, the examination of the tissue-specific distribution of these alternately spliced mRNAs using polymerase chain reaction amplification of cDNA coupled with Southern blotting revealed that each spliced variant had a unique tissue distribution. PMCA1b and PMCA4a were present in all tissues examined. PMCA1a, PMCA1b, and PMCA4b were expressed in excitable tissues, whereas PMCA1d was expressed only in muscle tissues. PMCA2 was found in liver, adrenal gland, spinal cord, and brain. PMCA3a was present in spinal cord, and PMCA3b in thymus, adrenal gland, spinal cord, and brain. The mRNA for a new spliced variant of PMCA4 (PMCA4b) was detected in this study. Complementary DNAs for this isoform were isolated and characterized from human and bovine brain. This alternately spliced form of the PMCA4 mRNA contained an exon inserted at the splice junction immediately following the sequence encoding the calmodulin-binding domain. As has also been shown for PMCA1a, this insertion produced a shift in the reading frame at the 3'-end of the PMCA4 mRNA that yielded a sequence encoding a Ca(2+)-ATPase lacking a large portion of the C-terminal regulatory domain. When the human PMCA4 gene spanning this region of variable exon splicing was sequenced, it confirmed the intron-exon boundaries where alternate splicing occurs to produce PMCA4a and PMCA4b.
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PMID:Analysis of the tissue-specific distribution of mRNAs encoding the plasma membrane calcium-pumping ATPases and characterization of an alternately spliced form of PMCA4 at the cDNA and genomic levels. 153 51

We have used four mutant calmodulins to study the regulation of human erythrocyte Ca(2+)-ATPase by the calmodulin-dependent pathway; the conserved Glu at position 12 in each of the four Ca(2+)-binding domains of calmodulin (Glu31, Glu67, Glu104, or Glu140) was replaced by Ala. At pCa 7, where unmodified calmodulin maximally activates the erythrocyte Ca(2+)-ATPase, all four mutants stimulated Ca(2+)-ATPase activity to the same maximal velocity. However, the concentrations of mutant calmodulins required for half-maximal activation (KCaM) were significantly higher than that for unmodified calmodulin and were strongly dependent on the domain in which the mutated Glu was located; substitution in either the first or second Ca(2+)-binding domain had little effect (2-3-fold increase in KCaM), whereas substitution in either the third or fourth domain resulted in a dramatic, 25-71-fold increase in KCaM. The same order of sensitivity was observed when the Ca2+ dependence of enzyme activation was measured at a constant 100 nM concentration of mutant calmodulin. These data point to dramatic differences in the functional significance of the replacement of the Glu at position 12 in each of the four Ca(2+)-binding domains for activation of the Ca(2+)-ATPase. The 2 Glu residues located in the carboxyl-terminal half of calmodulin (particularly Glu140) are crucial for activation of the Ca(2+)-ATPase at physiologically significant Ca2+ concentrations.
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PMID:Regulation of the erythrocyte Ca(2+)-ATPase by mutant calmodulins with Glu----Ala substitutions in the Ca(2+)-binding domains. 153 52

A Ca(2+)-ATPase with an apparent Km for free Ca2+ = 0.23 microM and Vmax = 44 nmol Pi/mg/min was detected in a rat parotid plasma membrane-enriched fraction. This Ca(2+)-ATPase could be stimulated without added Mg2+. However, the enzyme may require submicromolar concentrations of Mg2+ for its activation in the presence of Ca2+. On the other hand, Mg2+ could substitute for Ca2+. The lack of a requirement for added Mg2+ distinguished this Ca(2+)-ATPase from the Ca(2+)-transporter ATPase in the plasma membranes and the mitochondrial Ca(2+)-ATPase. The enzyme was not inhibited by several ATPase inhibitors and was not stimulated by calmodulin. An antibody which was raised against the rat liver plasma membrane ecto-ATPase, was able to deplete this Ca(2+)-ATPase activity from detergent solubilized rat parotid plasma membranes, in an antibody concentration-dependent manner. Immunoblotting analysis of the pellet with the ecto-ATPase antibody revealed the presence of a 100,000 molecular weight protein band, in agreement with the reported ecto-ATPase relative molecular mass. These data demonstrate the presence of a Ca(2+)-ATPase, with high affinity for Ca2+, in the rat parotid gland plasma membranes. It is distinct from the Ca(2+)-transporter, and immunologically indistinguishable from the plasma membrane ecto-ATPase.
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PMID:A Ca(2+)-ATPase from rat parotid gland plasma membranes has the characteristics of an ecto-ATPase. 153 8

The effects of calmidazolium and compound 48/80 were studied in four different states of activation of the purified Ca(2+)-ATPase from cardiac sarcolemma: "basal" or unactivated, activated by calmodulin, activated by phosphatidylserine, and activated by controlled trypsinization. When assayed in the presence of phosphatidylcholine as the sole phospholipid (basal state), the purified enzyme was resistant to inhibition by calmidazolium (0.1 to 3 microM). In the same range, calmidazolium inhibited the enzyme activated by controlled proteolysis as well as the calmodulin-activated enzyme regardless of the calmodulin concentration. The phosphatidylserine-activated enzyme was inhibited at higher calmidazolium concentrations due to non-specific trapping of the inhibitor by the excess of phospholipid. Addition of calmidazolium did not modify the K0.5 for calcium activation of ATP hydrolysis by the enzyme. The inhibition by calmidazolium was counteracted by Pi. Compound 48/80 also had no effect on the enzyme when only phosphatidylcholine was present and, like calmidazolium, it inhibited the calmodulin-activated enzyme and the phosphatidylserine-activated enzyme. The apparent Ki for inhibition by compound 48/80 was dependent on the calmodulin concentration. However, the enzyme activated by controlled trypsinization was insensitive to compound 48/80. Binding of 48/80 to the enzyme in the presence of phosphatidylserine or calmodulin reversed the increased affinity for Ca2+ caused by these activators.
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PMID:Distinct mechanisms of inhibition of purified cardiac sarcolemma Ca(2+)-ATPase by two calmodulin antagonists. 153 19


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