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)

Microtubules have been implicated as being necessary for the secretion of insulin from beta-cells, although the mechanism by which cytoplasmic microtubules contribute to the release of insulin is unknown. Kinesin is a microtubule-dependent adenosine triphosphatase (ATPase) that is thought to be responsible for the intracellular transport of vesicles and organelles. In this manuscript, the purification and preliminary characterization of a beta-cell form of kinesin is described. A 120-kilodalton antikinesin-reactive polypeptide was identified on blots when cultured insulinoma tumor cell lines were subjected to immunoblot analysis using monoclonal antibodies specific for the heavy chain of mammalian kinesin. The beta-cell form of kinesin was isolated from solid rat insulinoma tumors by cosedimentation of the kinesin with microtubules from tissue homogenates in the presence of adenylyl-imidodiphosphate. The beta-cell kinesin was further purified by gel filtration chromatography, and then the pure enzyme was characterized using in vitro assays. Although beta-cell kinesin showed little ATPase activity alone, the enzyme exhibited considerable ATP hydrolysis activity in the presence of taxol-stabilized microtubules. Moreover, in motility assays beta-cell kinesin was able to translocate microtubules across microscope coverslips in the presence of Mg(2+)-ATP. In summary, we report the identity of a novel islet beta-cell form of the microtubule-dependent ATPase kinesin and suggest a possible contribution of the microtubule cytoskeleton in insulin secretion.
...
PMID:The identification, purification, and characterization of a pancreatic beta-cell form of the microtubule adenosine triphosphatase kinesin. 161 13

Early biosynthesis of short-life ATP was observed in plasma membranes of target cells stimulated by insulin or other polypeptide growth factors in the presence of all components of aerobic phosphorylation and cytochrome c. The effect is always mediated by the binding of insulin or growth factors to specific receptors. Erythrocyte plasma membranes are a convenient model to study the phenomenon. Insulin-stimulated synthesis of the plasma membrane "signal" ATP in an amount of 1-10 nM is potentized by ionophores carbonyl cyanide p-trifluorometoxyphenylhydrazone and monensin and inhibited by amiloride and ouabain. It is supposed that the plasma membrane "signal" ATP readily generated in response to a growth or mitogenic factor is an "amplifier" or "coupling agent" in the transduction of a signal to growth, proliferation, and mitogenesis. Biosynthesis of the plasma membrane "signal" ATP seems to be associated with partial reversion of Na+, K+ -ATPase with the participation of the plasma membrane redox chain as a proton generator.
...
PMID:ATP synthesis in plasma membrane enriched particles by the action of insulin and related growth factors. 162 80

This study was aimed at identifying the renal sites of the antinatriuretic action of insulin by evaluating whether this hormone may alter the function of Na-K-ATPase in specific nephron segments. For this purpose, possible actions of insulin on the rate of 86Rb uptake were evaluated in vitro on single segments of proximal convoluted tubule (PCT), thick ascending limb, and collecting tubule microdissected from collagenase-treated kidneys of normal rats. Results indicate that physiological concentrations of insulin inhibited by 44% the initial rate of ouabain-sensitive 86Rb uptake in the medullary and cortical thick ascending limb, whereas it increased it by 40% in proximal tubules and by 60% in both cortical and medullary collecting tubules. The kinetics and dose dependence of insulin actions were different in the thick ascending limb, the PCT, and the collecting tubule, with the latter less sensitive but displaying an earlier response to insulin than the PCT and the thick ascending limb.
...
PMID:Sites of antinatriuretic action of insulin along rat nephron. 163 41

This study examines the ontogenesis of insulin receptors in human cerebral cortex. Synaptosomal membrane fraction was obtained after subcellular fractionation of human brain tissue. The 24 cases studied were classified according to the statistical differences found in: Group I, pre-term, up to 30 weeks of gestation; group II, full-term and newborns; group III from one year to adulthood. Scatchard plots of insulin binding to brain membranes were curvilinear and showed a decrease in insulin receptor number as a function of age with slight differences in affinity. Receptor number were 3.0 +/- 0.8 pmol/mg in Group I, 0.6 +/- 0.14 pmol/mg and 0.2 +/- 0.024 pmol/mg in Groups II and III respectively. Values of 5'nucleotidase and Na+ K+ ATPase activities, were similar in all groups, which indicates that the purity of the fraction used for binding was similar in each group. According to the ontogenic profile in insulin binding described in this work, it may be assumed that the higher concentration of insulin receptors in human brain during the fetal period can determine some insulin action in this early stage of maturation, even though the functionality of these receptors remains to be elucidated.
...
PMID:Ontogenesis of insulin receptors in human cerebral cortex. 164 51

Insulin augments Na(+)-K(+)-ATPase activity in skeletal muscles. It has been proposed that the sequence of events is activation of Na(+)-H+ antiporter, increased intracellular Na+ concentration ( [Na+]i), and stimulation of Na(+)-K+ pump. We have used isolated rat soleus muscles to test this hypothesis. Insulin increased the ouabain-suppressible K+ uptake in a dose- and time-dependent manner. The maximal effect was observed at 50-100 mU/ml insulin. Stimulation of K+ uptake was accompanied by increased specific [3H]ouabain binding and lowered [Na+]i. The ionophore monensin, which promotes Na(+)-H+ exchange, also increased the rate of ouabain-suppressible K+ uptake in soleus muscle, with a maximal effect obtained at 10-100 microM ionophore. However, this increase was accompanied by an elevation of [Na+]i. In the presence of 10-100 microM monensin, addition of 100 mU/ml insulin further increased K+ uptake but reduced [Na+]i. The effect on K+ uptake was additive. Ouabain (10(-3) M) completely suppressed the effect of insulin on [Na+]i. Insulin had no effect on the magnitude or the time course of insulin stimulation of K+ uptake. Thus equal stimulation of Na(+)-K(+)-ATPase by insulin was observed when [Na+]i was elevated (under monensin) or lowered (under amiloride). These data suggest that activation of Na(+)-K(+)-ATPase in soleus muscle by insulin is not secondary to stimulation of Na(+)-H+ antiporter.
...
PMID:Mechanism of insulin-induced activation of Na(+)-K(+)-ATPase in isolated rat soleus muscle. 165 50

The (Na+,K+) ATPase in plasma membranes isolated from rat adipocytes is insensitive to insulin (Lytton J., Lin, J.C., and Guidotti, G. (1985) J. Biol. Chem. 260, 1177-1184). For this reason, the characteristics of the (Na+,K+) pump in adipocyte ghosts, prepared by hypotonic lysis of adipocytes (Rodbell, M. (1967) J. Biol. Chem. 242, 5744-5750), were studied. Herein it is demonstrated that the (Na+,K+) pump in ghosts is identical to that described in isolated plasma membranes, sharing the following characteristics: 1) the Ki values for ouabain are 1.3 x 10(-7) M and 4.5 x 10(-5) M for the alpha 2 and alpha 1 isozymes, respectively; 2) the K0.5 values for sodium are 11.4 +/- 1.6 and 7.2 +/- 3.8 mM for the alpha 2 and alpha 1 isozymes, respectively; 3) both forms of the (Na+,K+) pump are insensitive to insulin stimulation, presumably because the activities are already maximal. The ghosts are not in an insulin-stimulated state because the activity of the glucose transporter is not increased as it is in ghosts prepared from insulin-treated cells. In addition, presented evidence demonstrates that ghost internal sodium concentration, [Na+]i, is very sensitive to changes in the activity of the (Na+,K+) pump. If the [Na+]i, of adipocytes is also very sensitive to the activity of the (Na+,K+) pump, the mechanism of insulin stimulation of the adipocyte (Na+,K+) pump requires reexamination.
...
PMID:Characterization of the adipocyte ghost (Na+,K+) pump. Insights into the insulin regulation of the adipocyte (Na+,K+) pump. 165 21

This study describes reduced motor nerve conduction velocity and increased resistance to hypoxia-induced conduction failure in sciatic nerves of rats after four weeks of streptozotocin-induced diabetes (both effects were significant at p less than 0.05). These changes occurred in the absence of any deficit in the steady-state ouabain-sensitive adenosine triphosphatase (ATPase) activity of sciatic nerve endoneurial homogenates. The addition of 10 nmol/l insulin to endoneurial homogenates from control animals resulted in a 34% increase in ouabain-sensitive ATPase activity and a 19% reduction in ouabain-insensitive ATPase activity (both p less than 0.01). This stimulation of ouabain-sensitive ATPase activity by insulin did not occur in homogenates from diabetic rats. Treating diabetic rats daily with the aldose reductase inhibitor, imirestat (1 mg/kg) improved nerve conduction velocity (p less than 0.05) but was without effect upon the resistance to hypoxic conduction blockade or the deficit in insulin-stimulated ouabain-sensitive ATPase activity. These data suggest that in streptozotocin-diabetic rats the functional disorders of reduced motor nerve conduction velocity and increased resistance to hypoxic conduction blockade do not share a common aetiology and that impaired nerve conduction is not related to reduced maximal potential ouabain-sensitive ATPase activity.
...
PMID:Aldose reductase inhibition with imirestat-effects on impulse conduction and insulin-stimulation of Na+/K(+)-adenosine triphosphatase activity in sciatic nerves of streptozotocin-diabetic rats. 165 57

The (Ca2+ + Mg2+) ATPase which serves as a Ca2+ pump in the kidney basolateral membranes is essential to the maintenance of an intracellular Ca2+ concentration optimal for kidney function. Since atrial natriuretic peptide (ANP) is known to participate in the Ca2+ homeostasis mechanism, altered levels of ANP in diabetes may vary the pump activity and consequently the kidney function. In order to examine the modulatory role of ANP on (Ca2+ + Mg2+) ATPase in short- (6 weeks) and long-term (6 months) diabetes, rats were injected with streptozotocin (65 mg/kg body wt, i.v.). At 6 weeks, the plasma ANP was decreased whereas, ANP-receptor binding in the kidney basolateral membrane was increased. In contrast, there was an increased plasma ANP and decreased ANP receptor binding at 6 months. Insulin treatment to diabetic animals normalized these parameters. The (Ca2+ + Mg2+) ATPase activity was unchanged both at 6 weeks and 6 months. Our results demonstrate that the unchanged Ca2+ pump activity in short-term and long-term diabetes serves to maintain the Ca2+ homeostasis in the kidney cells and thus may maintain the hyperfiltration state in diabetes. Unaltered (Ca2+ + Mg2+) ATPase is achieved by the initial up-regulation and subsequent down-regulation of the ANP receptors.
...
PMID:(Ca2+ + Mg2+) ATPase activity in kidney basolateral membrane in diabetes: role of atrial natriuretic peptide. 165

Erythrocytes of diabetic subjects (non-insulin dependent) were found to have eight- to ten-fold higher levels of endogenously formed thiobarbituric acid reactive malonyldialdehyde (MDA), thirteen-fold higher levels of phospholipid-MDA adduct, 15-20% reduced Na(+)-K(+)-ATPase activity with unchanged Ca+2-ATPase activity, as compared with the erythrocytes from normal healthy individuals. Incubation of normal erythrocytes with elevated concentrations (15-35 mM) of glucose, similar to that present in diabetic plasma, led to the increased lipid peroxidation, phospholipid-MDA adduct formation, reduction of Na(+)-K(+)-ATPase (25-50%) and Ca+2-ATPase (50%) activities. 2-doxy-glucose was 80% as effective as glucose in the lipid peroxidation and lipid adduct formation. However, other sugars, such as fructose, galactose, mannose, fucose, glucosamine and 3-O-methylmannoside, and sucrose, tested at a concentration of 35 mM, resulted in reduced (20-30%) lipid peroxidation without the formation of lipid-MDA adduct. Kinetic studies show that reductions in Na(+)-K(+)-ATPase and Ca+2-ATPase activities precede the lipid peroxidation as the enzyme inactivation occur within 30 min of incubation of erythrocytes with high concentration (15-35 mM) of glucose, while lipid peroxidation product, MDA appears at 4 hr and lipid-MDA adducts at 8 hr. The lipoxygenase pathway inhibitors, 5,8,11-eicosatriynoic acid and Baicalein (5,6,7-trihydroxyflavone), reduced the glucose-induced lipid peroxidation by 30% and MDA-lipid adduct formation by 26%. Indomethacin, a cyclooxygenase pathway inhibitor, had no discernible effect on the lipid peroxidation in erythrocytes. However, the inhibitors of lipid peroxidation, 3-phenylpyrazolidone, metyrapone, and the inhibitors of lipoxygenase pathways did not ablate the glucose-induced reduction of Na(+)-K(+)-ATPase and Ca+2-ATPase activities in erythrocytes. Erythrocytes produce 15-HETE (15-hydroxy-eicosatetraenoic acid), which is augmented by glucose. These results suggest that the formation of lipoxygenase metabolites potentiate the glucose-induced lipid peroxidation and that the inactivation of Na(+)-K(+)-ATPase and Ca+2-ATPase occurs as a result of non-covalent interaction of glucose with these enzymes.
...
PMID:Glucose induces lipid peroxidation and inactivation of membrane-associated ion-transport enzymes in human erythrocytes in vivo and in vitro. 165 8

Alterations in erythrocyte plasma membrane properties (enzymatic activities and membrane fluidity) have been observed in patients affected by insulin-dependent diabetes mellitus (IDDM) and non-insulin-dependent diabetes mellitus (NIDDM). In order to verify whether these alterations are present also in gestational diabetes mellitus (GDM) we studied the plasma membranes obtained from two different cellular types (erythrocyte from both mother and cord blood and placenta syncytiothrophoblast cell) of 16 healthy pregnant women and 15 women affected by GDM. The following determinations were performed on the membrane preparations: Na+/K(+)-ATPase activity, acetyl-cholinesterase (AchE) activity, membrane fluidity and cholesterol:phospholipid ratio. We observed a reduction of both enzymatic activities and a decrease of membrane fluidity in maternal and cord blood erythrocytes and in syncytiotrophoblast plasma membranes in GDM pregnant women in comparison with controls. The cholesterol to phospholipid ratio was significantly lower in the erythrocyte membranes of women affected by GDM than in normal pregnant women, while it was increased in the cord blood erythrocyte membranes and in placental membranes in GDM in comparison with controls. The present study found, in GDM patients, a membrane alteration similar to the abnormality reported in IDDM and NIDDM (i.e. decreased Na+/K(+)-ATPase activity), while opposite modifications were observed with regard to other membrane activities and properties. The different membrane alterations observed in GDM with respect to IDDM and NIDDM might be linked to the different degree of metabolic control, on the contrary the reduced Na+/K(+)-ATPase activity might be a primary event in the pathogenesis of diabetes mellitus per se and might constitute a signal of high risk of developing the disease later in the women affected by GDM during pregnancy.
...
PMID:Modifications induced by gestational diabetes mellitus on cellular membrane properties. 165 18


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>

---