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)

In skeletal muscle insulin induces the translocation of both the GLUT4 glucose transporter and the alpha 2 subunit of the Na,K-ATPase from an intracellular membrane (IM) compartment to the plasma membrane (PM). Fractionation studies of rat skeletal muscle using a discontinuous sucrose gradient have indicated that the insulin-induced loss of both proteins occurs from a fraction containing intracellular membranes (IM) of common density. This raises the possibility that both proteins may be colocalized in a single intracellular compartment or are present in separate membrane vesicles that are of similar buoyant density. In this study we report the membrane vesicles from the insulin-responsive IM fraction can in fact be separated on the basis of differences in their sedimentation velocities; immunoblot analyses of fractions collected from a sucrose velocity gradient revealed the presence of two separate peaks for GLUT4 and the alpha 2 subunit of the Na,K-ATPase. One of these peaks representing a fast sedimenting population of vesicles (with a sedimentation coefficient of 2697 +/- 57 S) reacted against antibodies to the alpha 2 subunit of the Na,K-ATPase, whereas, the second peak contained a population of much slower sedimenting vesicles (with a sedimentation coefficient of 209 +/- 4 S) were practically devoid of the alpha 2-subunit. By contrast, the slow sedimenting vesicles were enriched by approximately 32-fold in GLUT4 relative to the starting IM fraction when the fractional protein content was taken into account. Immunoprecipitation of GLUT4-containing vesicles from the insulin-sensitive IM fraction revealed that no immunoreactivity towards either the alpha 2 or the beta 1 subunits of the Na,K-ATPase could be observed, signifying that the insulin-responsive subunits of the Na,K-ATPase and GLUT4 were present in different membrane vesicles and that it was unlikely, therefore, that the insulin-induced redistribution of these proteins to the PM occurs from a common intracellular pool.
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PMID:Sedimentation and immunological analyses of GLUT4 and alpha 2-Na,K-ATPase subunit-containing vesicles from rat skeletal muscle: evidence for segregation. 861 24

Cells can rapidly and reversibly alter solute transport rates by changing the kinetics of transport proteins resident within the plasma membrane. Most notably, this can be brought about by reversible phosphorylation of the transporter. An additional mechanism for acute regulation of plasma membrane transport rates is by the regulated exocytic insertion of transport proteins from intracellular vesicles into the plasma membrane and their subsequent regulated endocytic retrieval. Over the past few years, the number of transporters undergoing this regulated trafficking has increased dramatically, such that what was once an interesting translocation of a few transporters has now become a widespread modality for regulating plasma membrane solute permeabilities. The aim of this article is to review the models proposed for the regulated trafficking of transport proteins and what lines of evidence should be obtained to document regulated exocytic insertion and endocytic retrieval of transport proteins. We highlight four transporters, the insulin-responsive glucose transporter, the antidiuretic hormone-responsive water channel, the urinary bladder H(+)-ATPase, and the cystic fibrosis transmembrane conductance regulator Cl- channel, and discuss the various approaches taken to document their regulated trafficking. Finally, we discuss areas of uncertainty that remain to be investigated concerning the molecular mechanisms involved in regulating the trafficking of proteins.
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PMID:Role of membrane trafficking in plasma membrane solute transport. 751 93

Given the sequence of transporters or channels of unknown secondary structure, it is usual to predict their putative transmembrane regions as alpha-helical. However, recent evidence for a facilitative glucose transporter (GLUT1) appears inconsistent with such predictions, which has led us to propose an alternative folding model for GLUTs based on the 16-stranded antiparallel beta-barrel of porins. Here we apply the same predictive algorithms we used for GLUTs to several other membrane proteins. For some of them, a high-resolution structure has been derived (beta-barrels: Rhodobacter capsulatus and Escherichia coli porins; multihelical: colicin A, bacteriorhodopsin, and reaction center L chain); we use them to test the prediction procedures. The other proteins we analyze (GLUT1, CHIP28, acetylcholine receptor alpha subunit, lac permease, Na(+)-glucose cotransporter, shaker K+ channel, sarcoplasmic reticulum Ca(2+)-ATPase) are representative of classes of similar membrane proteins. As with GLUTs, we find that the predicted transmembrane segments of these proteins are consistently shorter than expected for transmembrane spanning alpha-helices, but are of the correct length and number for the proteins to fold instead as porin-like beta-barrels.
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PMID:Are most transporters and channels beta barrels? 753 68

The expression of sodium-potassium pumps and glucose transporters in pure adipocyte plasma membranes from a hyperthyroid animal model was studied. Hyperthyroidism was induced by enteral administration of five doses of 90 micrograms of triiodothyronine every second day to 8-week-old rats. Following isolation of epididymal adipocytes, 3-O-methylglucose transport was measured and the number of Na/K-ATPase-(alpha 1- and alpha 2-isoforms) and glucose transporter (GLUT1 and GLUT4) molecules in sheets of adipocyte plasma membrane were determined by quantitative immunoelectron microscopy, using gold labelling. Maximal in vitro insulin stimulation of adipocytes increased the glucose transport rate and the amount of GLUT4 in the plasma membrane 15-fold, whereas the amount of alpha 2 was unaffected. In adipocytes from hyperthyroid rats, mean adipocyte volume was decreased by 18% and the quantities of GLUT4 per unit area of plasma membrane (maximal insulin stimulation) and of alpha 2 were decreased by 19% and 15%, respectively. Thus, hypotrophia of fat tissue in the hyperthyroid state is associated with a decreased expression in the plasma membrane of the glucose transporter GLUT4 and the alpha 2-isoform of Na/K-ATPase.
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PMID:Quantity of Na/K-ATPase and glucose transporters in the plasma membrane of rat adipocytes is reduced by in vivo triiodothyronine. 758 95

Understanding the molecular mechanisms involved in the regulation of glucose transport into human muscle is necessary to unravel possible defects in glucose uptake associated with insulin resistance in humans. Here we report a strategy to subfractionate human skeletal muscle biopsies (0.5 g) removed from vastus lateralis during a euglycemic insulinemic clamp procedure. A sucrose gradient separated total membranes into five fractions. Fraction 25 (25% sucrose) contained the plasma membrane markers alpha 1- and alpha 2-subunits of the Na(+)-K(+)-adenosinetriphosphatase and the GLUT-5 hexose transporter, recently immunolocalized to the cell surface of human skeletal muscle. The dihydropyridine receptor, a transverse tubule marker, was present exclusively in this fraction. The GLUT-4 glucose transporter was more concentrated in fraction 27.5 (27.5% sucrose) and largely diminished in plasma membrane markers. Open skeletal muscle biopsies were removed before and 30 min after clamping insulin to 550 pM. This increased GLUT-4 protein by 1.61-fold in fraction 25 and lowered it by 50% in fraction 27.5. Thus physiological concentrations of insulin induce translocation of glucose transporters from an internal membrane pool to surface membranes in human skeletal muscle.
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PMID:Insulin induces translocation of GLUT-4 glucose transporters in human skeletal muscle. 773 59

The GLUT4 glucose transporter and the alpha 2 subunit of the Na+,K(+)-ATPase of rat skeletal muscle are two proteins which redistribute from intracellular membranes to plasma membranes following in vivo insulin stimulation. Here we show that although both proteins co-segregate after subcellular fractionation of unstimulated rat hindlimb muscles, they do not share the same intracellular residence inside the muscle fibre. By immunogold single- and double-labeling on ultrathin muscle cryosections with specific antibodies, the GLUT4 glucose transporter and the Na+,K(+)-ATPase alpha 2 subunit were observed on different vesicular structures within the cell. GLUT4 was detected on subsarcolemmal and perinuclear membranes, and at the junction between myofibrillar A and I bands where triads are localized. The alpha 2 subunit of the Na+,K(+)-ATPase was observed at the plasma membrane and in distinct subsarcolemmal vesicles and intermyofibrillar membranes. Quantitative analysis of double-labeling of GLUT4 and Na+,K(+)-ATPase alpha 2 subunit revealed that less than 6% of the two proteins co-localize in the same continuous vesicular structures. The differential intracellular localization of the two proteins was further confirmed by immunopurification of GLUT4-containing membranes from muscle homogenates, in which the alpha 2 subunit of the Na+,K(+)-ATPase was found only at the same extent as the alpha 1 subunit of the enzyme, a protein exclusively present at the plasma membrane.
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PMID:The GLUT4 glucose transporter and the alpha 2 subunit of the Na+,K(+)-ATPase do not localize to the same intracellular vesicles in rat skeletal muscle. 778 25

The effect of oral vanadate on intestinal sodium-dependent glucose transport and 6-phosphofructo-1-kinase (EC 2.7.1.11) activity was examined in male Sprague-Dawley rats following a 30-day period of non-treated streptozotocin-induced diabetes. Non-treated diabetic rats were hyperglycaemic and demonstrated increased intestinal sodium-dependent glucose transport and Na,K-ATPase activity compared with controls. These increases were associated with a significant decrease in the total activity and activity ratios (activity at 0.5 mmol/l fructose 6-phosphate at pH 7.0/activity at pH 8.0) of intestinal 6-phosphofructo-1-kinase and decreased levels of fructose 2,6-bisphosphate. Supplementation of drinking water with vanadate (0.5 mg/ml) resulted in a rapid decline in blood glucose levels to a slightly hyperglycaemic level. Jejunal glucose transport and Na,K-ATPase activity were normalized after 48 h of vanadate treatment. In contrast, ileal glucose transport was significantly reduced 12 h following beginning vanadate treatment even though Na,K-ATPase activity did not normalize until 36 h later. Km was significantly decreased in both jejunum and ileum by vanadate treatment indicating an increased affinity of the sodium-dependent intestinal glucose transporter for glucose. 6-phosphofructo-1-kinase total activity and susceptibility to ATP inhibition was completely restored after 12 h of vanadate treatment. This increase was associated with a rise in fructose 2,6-bisphosphate levels. Fasting rats for 12 h had no effect on glucose transport or 6-phosphofructo-1-kinase activity, indicating the anorectic effect of vanadate was not responsible for changes in either parameter. In contrast, cycloheximide prevented both the rise in 6-phosphofructo-1-kinase activity and the rise in fructose 2,6-bisphosphate levels, and the subsequent reduction in glucose transport, indicating a requirement for protein synthesis. The removal of vanadate resulted in an immediate return to pre-treatment blood glucose levels. In contrast, intestinal glucose transport and 6-phosphofructo-1-kinase activity remained at treatment levels up until 72 h, indicating that oral vanadate treatment can have prolonged beneficial effects on intestinal function. In conclusion, the treatment of streptozotocin-induced diabetic rats with oral vanadate results in an activation of 6-phosphofructo-1-kinase coupled with a normalization of intestinal sodium-dependent glucose transport. Vanadate may thus have a beneficial effect on intestinal function and may prove useful as oral adjunctive diabetic therapy.
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PMID:Vanadate treatment rapidly improves glucose transport and activates 6-phosphofructo-1-kinase in diabetic rat intestine. 779 80

This study was performed to determine the effect of cisplatin (cis-diamminedichloroplatinum II) on renal function in rabbits. Injection of a single i.p. dose of 4 mg/kg cisplatin caused an increase in fractional excretion of Na+ and K+ and a decrease in urine osmolality (Uosm), free-water reabsorption, (TcH2O), and urine to plasma creatinine ratio (U/Pcr). Urine flow was decreased following cisplatin treatment, which was accompanied by marked reduction in GFR. Cisplatin induced glucosuria, phosphaturia, and aminoaciduria. These results suggest that cisplatin results in impaired proximal tubular reabsorptive function and the renal concentrating defect. Cisplatin treatment impaired the accumulation of PAH and TEA and ouabain-sensitive oxygen consumption in renal cortical slices. Na(+)-K(+)-ATPase activity in renal cortical microsomes and basolateral membrane vesicles was significantly depressed in cisplatin-treated animals. Cisplatin treatment did not affect the Na(+)-dependent uptake of glucose and L-glutamate by brush-border membrane vesicles (BBMV), but caused a significant decrease in Na(+)-dependent succinate and H(+)-dependent TEA uptake. Morphological observations showed that cisplatin caused a focal loss of the microvillus brush border. These results suggest that (1) cisplatin induces oliguric acute renal failure in rabbits and (2) glucosuria induced by cisplatin was not due to a direct impairment of glucose transporter in brush-border membranes but due to an inhibition of Na(+)-pump activity and a decrease in area for active glucose reabsorption in the proximal tubule.
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PMID:Effect of cisplatin on renal function in rabbits: mechanism of reduced glucose reabsorption. 783 66

The retinal pigment epithelium (RPE) is unique in that Na,K-ATPase is predominantly localized on its apical surface. We studied the distributions of Na,K-ATPase and glucose transporter GLUT1, insulin and transferrin receptors in developing rat RPE cells immunocytochemically. Na,K-ATPase, first detected in 17-day-old embryonic eyes, was already distributed predominantly on the apical surface. This reversed distribution of Na,K-ATPase was maintained throughout their life. Insulin receptor and transferrin receptor were distributed exclusively on the basolateral surface. By quantitative immunogold electron microscopic technique we found that glucose transporter GLUT1 is distributed almost equal in amount on both the apical and basolateral surfaces of RPE cells, thus presumably constructing an efficient pathway for glucose transport from the choriocapillaries to the neural retina through the blood-retinal barrier. These results suggest that in the RPE cells the intrinsic basolateral plasma membrane proteins are sorted out at least in three different ways.
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PMID:Immunocytochemical analyses of distributions of Na, K-ATPase and GLUT1, insulin and transferrin receptors in the developing retinal pigment epithelial cells. 806 44

In an earlier subcellular fractionation study of epithelial tissue (liver and pancreas), we demonstrated that the inositol 1,4,5-trisphosphate receptor (IP3R) is found in association with biochemically distinct cellular membranes, including the endoplasmic reticulum (ER) and plasma membrane (Sharp, A. H., Snyder, S. H., and Nigam, S. K. (1992) J. Biol. Chem. 267, 7444-7449). To further characterize epithelial IP3Rs, we have now employed cultured Madin-Darby canine kidney (MDCK) cells, a well studied tight polarized epithelial cell type. Indirect immunofluorescence with an antiserum which specifically recognizes IP3R in MDCK cells by immunoblotting and immunoprecipitation gave an ER-like staining pattern as well as a basolateral plasma membrane-like staining pattern, the latter being particularly evident in highly confluent monolayers. In sections of adult rat kidney tubules a similar staining pattern was observed. Interestingly, whereas known basolateral proteins (Na+,K(+)-ATPase and the facilitated glucose transporter) gave a continuous basolateral staining pattern, that seen for IP3R was discontinuous (punctate). A highly similar staining pattern was observed for the caveolar protein, caveolin, suggesting that the punctate basolateral plasma membrane-like staining pattern observed for IP3R reflects its localization to basolateral caveolae. Biotinylation of non-permeabilized and permeabilized MDCK cells, followed by immunoprecipitation of IP3R and detection with streptavidin, indicated that while most IP3R is localized to biotin-inaccessible compartments (i.e. ER), a fraction (10-20%) of IP3R was accessible to externally added biotin primarily from the basolateral side. This result is compatible with the dual ER and basolateral caveolar localization suggested by immunocytochemistry, although it does not exclude the presence of some IP3R in the basolateral plasma membrane as well. Solubility studies revealed IP3R to be considerably more insoluble than the basolateral proteins, Na+,K(+)-ATPase and the liver cell adhesion molecule, as well as the cytoskeletal proteins, ankyrin and fodrin. In the most insoluble fraction, IP3R was found along with caveolin, further supporting the notion that part of the cellular IP3R pool associates with caveolae. Since multiple localizations of IP3R within a cell might reflect the existence of multiple isoforms, polymerase chain reaction amplification of first strand cDNA with primers specific for the three isotypes of IP3R was performed. All three isoforms of IP3R were expressed in the homogeneous population of MDCK cells. The existence of distinct membrane localizations and multiple isoforms of IP3R within the same cell type suggests an explanation for the complex spatiotemporal patterns of Ca2+ release from inositol 1,4,5-trisphosphate-sensitive Ca2+ pools in epithelial and other cells.
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PMID:Epithelial inositol 1,4,5-trisphosphate receptors. Multiplicity of localization, solubility, and isoforms. 808 40


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