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)

We have characterized a gene, PPA1, adjacent to the yeast MAS2 gene. DNA sequence analysis of PPA1 predicts a hydrophobic protein of 23 kDa. This protein is homologous to the proteolipid of the bovine chromaffin granule proton ATPase and to the proteolipid of the yeast vacuolar proton ATPase. Gene disruption experiments indicate that the PPA1 protein is essential for viability in three unrelated yeast strains and important for optimal growth in a fourth strain.
...
PMID:A yeast protein, homologous to the proteolipid of the chromaffin granule proton-ATPase, is important for cell growth. 213 79

The catalytic domain of the vacuolar proton ATPase is composed of a hexamer of three A subunits and three B subunits. Here we describe the cloning and characterization of a cDNA isoform of subunit B, HO57, from an osteoclastoma cDNA library. HO57 is represented by three species of mRNA of 1.6, 2.6 and 2.8 kb and is expressed at low levels in a range of human tissues, but at significantly higher levels in brain, kidney and osteoclastoma, and is probably an ubiquitously expressed isoform. In contrast, the kidney-specific isoform has an mRNA of 2 kb and is specifically expressed at high levels only in kidney and, at a lower level, in placenta. Thus the HO57 isoform is integral to the vacuolar ATPase found in the general secretory system of all cells as well as in vacuolar-ATPase-rich sources such as neurones and osteoclasts, whereas both the kidney-specific isoform and HO57 are highly expressed in the kidney. Furthermore, we show by in situ hybridization that HO57 is the only isoform that is exclusively and highly expressed by osteoclasts.
...
PMID:Heterogeneity of vacuolar H(+)-ATPase: differential expression of two human subunit B isoforms. 794 39

The plasma membrane composition of virtually all eukaryotic cells is maintained and continually modified by the recycling of specific protein and lipid components. In the kidney collecting duct, urinary acidification and urinary concentration are physiologically regulated at the cellular level by the shuttling of proton pumps and water channels between intracellular vesicles and the plasma membrane of highly specialized cell types. In the intercalated cell, hydrogen ion secretion into the urine is modulated by the recycling of vesicles carrying a proton pumping ATPase to and from the plasma membrane. In the principal cell, the antidiuretic hormone, vasopressin, induces the insertion of vesicles that contain proteinaceous water channels into the apical cell membrane, thus increasing the permeability to water of the epithelial layer. In both cell types, 'coated' carrier vesicles are involved in this process, but whereas clathrin-coated vesicles are involved in the endocytotic phase of water channel recycling, the transporting vesicles in intercalated cells are coated with the cytoplasmic domains of the proton pumping ATPase. By a combination of morphological and functional techniques using FITC-dextran as an endosomal marker, we have shown that recycling endosomes from intercalated cells are acidifying vesicles but that they do not contain water channels. In contrast, principal cell vesicles that recycle water channels do not acidify their lumens in response to ATP. These non-acidic vesicles lack functionally important subunits of the vacuolar proton ATPase, including the 16 kDa proteolipid that forms the transmembrane proton pore. Because these endosomes are directly derived via clathrin-mediated endocytosis, our results indicate that endocytotic clathrin-coated vesicles are non-acidic compartments in principal cells. In contrast, recycling vesicles in intercalated cells contain large numbers of proton pumps, arranged in hexagonally packed arrays on the vesicle membrane. These pumps are inserted into the apical plasma membrane of A-type (acid-secreting) intercalated cells, and the basolateral plasma membrane of B-type (bicarbonate-secreting) cells in the collecting duct. Both apical and basolateral targeting of H(+)-ATPase-containing vesicles in these cells may be directed by microtubules, because polarized insertion of the pump into both membrane domains is disrupted by microtubule depolymerizing agents. However, the basolateral localization of other transporting proteins in intercalated cells, including the band 3-like anion exchanger and facilitated glucose transporters, is not affected by microtubule disruption.
...
PMID:Endosomal pathways for water channel and proton pump recycling in kidney epithelial cells. 814 5

The vacuolar proton ATPase (V-ATPase) translocates protons into intracellular organelles or across the plasma membrane of specialised cells such as osteoclast and renal intercalated cells. The catalytic site of the V-ATPase consists of a hexamer of three A subunits and three B subunits which bind and hydrolyse ATP and are regulated by accessory subunits C, D and E. cDNAs encoding subunits C, D, and E were cloned from human osteoclastoma, a tissue highly enriched in osteoclasts, as a first step in the characterisation of the V-ATPase used by the osteoclast. By Northern blot analysis only one mRNA species were detected for each of these subunits, which is consistent the constant transcription level in all tissues irrespective of the presence of specialised cells highly enriched in V-ATPases.
...
PMID:Cloning and tissue distribution of subunits C, D, and E of the human vacuolar H(+)-ATPase. 825 Sep 20

To examine the effect of extracellular matrix on osteoclast polarization, we focused on the actin organization in osteoclasts, using murine osteoclast-like multinucleated cells (OCLs) formed in cocultures of osteoblastic cells and bone marrow cells. When OCLs were cultured on either a plastic plate, calcified dentine, or calcium phosphate thin films in the presence of fetal bovine serum (FBS), they similarly formed ringed structures of F-actin dots (actin rings). However, OCLs placed on demineralized dentine or type I collagen gel matrix (collagen gel) failed to form actin rings. In the absence of FBS, actin ring formation in OCLs was induced on plastic plates coated with vitronectin, fibronectin, or type I collagen, but not on those coated with laminin, poly-L-lysine, or bovine serum albumin. Actin ring formation appeared to depend on integrins, since the GRGDS, but not the GRGES, peptide inhibited it in a dose-dependent manner. Moreover, immunoelectron microscopic examination revealed that vacuolar proton ATPase (V-ATPase) was localized along the apical membrane in much higher densities than the basolateral membrane in OCLs placed on plastic coverslips. In OCLs placed on collagen gel, however, V-ATPase was found to be distributed throughout the cytoplasm without polarity. These results suggest that actin ring formation in osteoclasts was dependent on matrix substrates, matrix proteins and integrins, and was closely related to osteoclast function.
...
PMID:Chemical and physical properties of the extracellular matrix are required for the actin ring formation in osteoclasts. 897 Aug 88

We characterized the Mycobacterium marinum phagosome by using a variety of endocytic markers to follow the path of the bacteria through a mouse macrophage cell line. Using a laser confocal microscope, we found that the majority of viable M. marinum cells were in nonacidic vacuoles that did not colocalize with the vacuolar proton ATPase (V-ATPase), the calcium-independent mannose-6-phosphate receptor (CI-M6PR), or cathepsin D. In contrast, heat-killed organisms and latex beads were in acidic vacuoles which contained the V-ATPase, the CI-M6PR, and cathepsin D. A population of vesicles that contained live M. marinum labeled with the lysosomal glycoprotein LAMP-1, but the percentage of vacuoles that labeled was lower than for heat-killed organisms or latex beads. When testing live and heat-killed Mycobacterium tuberculosis, we found levels of colocalization with LAMP- and cathepsin D comparable to those for the M. marinum isolate. We conclude that M. marinum, like M. tuberculosis, can circumvent the host endocytic pathway and reside in an intracellular compartment which is not acidic and does not fuse with lysosomes. In addition, we describe a system for sampling a large population of intracellular organisms by using a laser confocal microscope.
...
PMID:Differential trafficking of live and dead Mycobacterium marinum organisms in macrophages. 911 92

We have previously shown that granulocyte colony-stimulating factor (G-CSF ) delays spontaneous neutrophil apoptosis through activation of the vacuolar proton ATPase (v-ATPase). We have now examined the regulation of the v-ATPase in neutrophils exposed to G-CSF in vitro. When neutrophils were cultivated in the absence of G-CSF, the 57-kD cytosolic B subunit of the v-ATPase disappeared within 1 to 2 hours, its loss preceding the nuclear changes of apoptosis and coinciding with the onset of acidification. By contrast, in neutrophils cultured for 2 hours in the presence of G-CSF, the amount of the 57-kD subunit was similar to that in freshly isolated neutrophils. However, inhibition of protein synthesis with cycloheximide and actinomycin D led to loss of the 57-kD subunit even in the presence of G-CSF. These results indicated that ongoing protein synthesis was required to maintain the v-ATPase, and further suggested that G-CSF acted, at least in part, by maintaining synthesis of the 57-kD cytosolic subunit. G-CSF also promoted the translocation of the 57-and 33-kD cytosolic v-ATPase subunits to the membrane. Our findings suggested two coordinate mechanisms by which the activity of the v-ATPase could be increased by G-CSF: the synthesis of cytosolic v-ATPase subunits and their translocation to the membrane.
...
PMID:Granulocyte colony-stimulating factor upregulates the vacuolar proton ATPase in human neutrophils. 937 71

Tamoxifen has been reported to inhibit acidification of cytoplasmic organelles in mammalian cells. Here, the mechanism of this inhibition is investigated using in vitro assays on isolated organelles and liposomes. Tamoxifen inhibited ATP-dependent acidification in organelles from a variety of sources, including isolated microsomes from mammalian cells, vacuoles from Saccharomyces cerevisiae, and inverted membrane vesicles from Escherichia coli. Tamoxifen increased the ATPase activity of the vacuolar proton ATPase but decreased the membrane potential (Vm) generated by this proton pump, suggesting that tamoxifen may act by increasing proton permeability. In liposomes, tamoxifen increased the rate of pH dissipation. Studies comparing the effect of tamoxifen on pH gradients using different salt conditions and with other known ionophores suggest that tamoxifen affects transmembrane pH through two independent mechanisms. First, as a lipophilic weak base, it partitions into acidic vesicles, resulting in rapid neutralization. Second, it mediates coupled, electroneutral transport of proton or hydroxide with chloride. An understanding of the biochemical mechanism(s) for the effects of tamoxifen that are independent of the estrogen receptor could contribute to predicting side effects of tamoxifen and in designing screens to select for estrogen-receptor antagonists without these side effects.
...
PMID:A mechanism for tamoxifen-mediated inhibition of acidification. 1037 41

Vacuole fusion occurs in three stages: priming, in which Sec18p mediates Sec17p release, LMA1 (low M(r) activity 1) relocation, and cis-SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) complex disassembly; docking, mediated by Ypt7p and trans-SNARE association; and fusion of docked vacuoles. Ca(2+) and calmodulin regulate late stages of the reaction. We now show that the vacuole proton gradient, generated by the vacuolar proton ATPase, is needed for trans-SNARE complex formation during docking and hence for the subsequent LMA1 release. Though neither the vacuolar Pmc1p Ca(2+)-ATPase nor the Vcx1p Ca(2+)/H(+) exchanger are needed for the fusion reaction, they participate in Ca(2+) and Delta mu(H)(+) homeostasis. Fusion itself does not require the maintenance of trans-SNARE pairs.
...
PMID:Vacuole acidification is required for trans-SNARE pairing, LMA1 release, and homotypic fusion. 1050 Jan 53

Short periods of ischemia followed up by reperfusion are known to protect the heart against injury caused by a subsequent sustained ischemia. This phenomenon, known as ischemic preconditioning, has also been recently shown to reduce ischemic liver damage, but the mechanisms involved are still unknown. By using isolated hepatocytes as an in vitro model of liver preconditioning, we have investigated the possible effect of preconditioning on intracellular pH and Na(+) homeostasis. Freshly isolated rat hepatocytes were preconditioned by 10 minutes of incubation under hypoxic conditions followed up by 10 minutes of reoxygenation and subsequently exposed to 90 minutes of hypoxia. Although preconditioning did not ameliorate adenosine triphosphate (ATP) depletion, preconditioned hepatocytes exhibited an increased resistance to cell killing during hypoxic incubation. Intracellular acidosis and Na(+) accumulation developing during hypoxia were appreciably reduced in preconditioned cells. The effects of preconditioning on intracellular pH, Na(+) homeostasis, and cytotoxicity were mimicked by stimulating protein kinase C (PKC) with 4beta-phorbol-12-myristate-13-acetate (PMA) or 1,2 dioctanoyl-glycerol (1,2 DOG). Conversely, inhibiting PKC with chelerythrine or blocking vacuolar proton ATPase (V-ATPase) with bafilomycin A(1) abolished the protection given by preconditioning or by PMA treatment on hypoxic acidosis, Na(+) overload, and hepatocyte killing. Similarly, the addition of Na(+) ionophore monensin also reverted the cytoprotection exerted by preconditioning. This indicated that ischemic preconditioning of isolated hepatocytes decreased cell killing during hypoxia by preventing intracellular Na(+) accumulation. We propose that, after preconditioning, the stimulation of PKC might activate proton extrusion through V-ATPase, thus, limiting intracellular acidosis and Na(+) overload promoted by Na(+)-dependent acid buffering systems.
...
PMID:Ischemic preconditioning reduces Na(+) accumulation and cell killing in isolated rat hepatocytes exposed to hypoxia. 1061 42


1 2 3 Next >>

---