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)

The process of enlargement of the heart due to overload involves a significant reconstitution of the organ including myocytes and intracellular constituents. We demonstrated the distribution of two types of cardiac myosin heavy chains (HC alpha and HC beta) in the human heart using monoclonal antibodies. The ventricle comprised mainly HC beta which has low ATPase activity, whereas the atrium was predominantly composed of HC alpha which has high ATPase activity. We also demonstrated isozymic transition of HC alpha to HC beta in the human atrium and ventricle by hemodynamic overload, regarded as a compensatory mechanism to meet an increased demand in work. To examine the molecular mechanism for the expression of these HCs, we have isolated human HC alpha and HC beta cDNA clones from a fetal heart cDNA library. Comparison of the nucleotide and amino acid sequences deduced from the DNA between these cDNA clones showed 91 and 96% homology, respectively. Using HC alpha and HC beta gene-specific sequences, we demonstrated that the transition of HC alpha to HC beta in the overloaded human heart was induced by the expression of HC beta-gene. To determine the role of cellular oncogenes in the process of cardiac growth and hypertrophy, we examined the expression pattern of eight cellular oncogenes during the developmental stage and pressure-overloaded hypertrophy of the rat heart by Northern blot analysis. c-fos, c-myc and c-Ha-ras were expressed in the heart in response to pressure overload and in a stage-specific manner, suggesting that these cellular oncogenes participate in the normal developmental process and hypertrophy of the heart. We also cloned the genes of which expression level was rapidly changed by pressure overload by differential hybridization technique. Our results suggest that clone 4 may be involved in the molecular mechanism for the development of cardiac hypertrophy due to overload.
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PMID:Molecular adaptation to pressure overload in human and rat hearts. 253 42

An increase in cell size and protein content is characteristic of cells undergoing hypertrophy and of replicating cells prior to DNA synthesis. Cell enlargement in the two situations could be regulated by similar early events with an interruption of the cell cycle occurring in hypertrophy, or the two processes could be uncoupled. In vivo models were used to compare hypertrophy induced by unilateral nephrectomy and hyperplasia induced by folic acid injection in rabbit renal cortical cells. Within 48 hr, cell volume increased in both groups but the number of cells in the cell cycle and DNA synthesis was increased only after folic acid. Patterns of mRNA expression of the following three groups of cell cycle-dependent genes were analyzed: (i) protooncogenes (c-fos, c-myc, and c-Ha-ras), (ii) structural protein genes (vimentin and beta-actin), and (iii) transport protein genes (Na+, K+-ATPase, ADP-ATP translocase, and calcyclin). mRNAs for all genes, except calcyclin and c-Ha-ras, were detected in controls. Folic acid generally induced rapid, transient increases in mRNA levels, but after unilateral nephrectomy, expression of most mRNAs showed a gradual, progressive increase. These data indicate that gene expression in the early stages of cell enlargement differs in cells destined to undergo proliferation vs. hypertrophy. The term "sustained message amplification" is proposed to describe the hypertrophied cell.
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PMID:Patterns of mRNA expression during early cell growth differ in kidney epithelial cells destined to undergo compensatory hypertrophy versus regenerative hyperplasia. 341 24

In this report, it is shown that the platelet-activating factor (PAF) induced, in human B lymphoblastoid cells, 86Rb+ influx and efflux suggesting that it activated a K+ channel. Opening of this channel was dependent on PAF-induced Ca2+ mobilization. Ionomycin and thapsigargin--a specific inhibitor of (Ca(2+)-Mg2+)-ATPase--mimicked the effect of PAF both on intracellular calcium and activation of the channel. This channel was inhibited by charybdotoxin, high doses of tetraethylammonium and barium but was insensitive to apamin, 4-aminopyridine. These features indicate that PAF activated a Ca(2+)-dependent K+ channel. In these cells, PAF also induced the expression of c-fos oncogene. This effect was not affected by charybdotoxin indicating that this channel is not involved in the control of early gene transcription.
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PMID:Platelet-activating factor activates a Ca(2+)-dependent K+ channel which is not involved in c-fos expression in human B lymphoblastoid cells. 750 33

Among the proto-oncogenes examined by northern blot analysis, c-myc, c-Ha-ras, c-fos, and c-raf-1 have been reported to be activated in rat liver cell carcinomas. However, there are relatively few reports on protooncogene expression in altered hepatic foci (AHF) early during hepatocarcinogenesis in the rat. In this study, diethylnitrosamine (DEN) at doses ranging from 10 to 200 mg/kg was used to initiate and phenobarbital (0.05%) to promote AHF in rats. AHF were detected by the presence of the marker enzymes glutathione s-transferase, placental form (GST-P); gamma-glutamyltranspeptidase (GGT); glucose-6-phosphatase (G6Pase); and canalicular adenosine triphosphatase (ATPase). Proto-oncogene expression in individual AHF was investigated by in situ hybridization (ISH). ISH for the mRNAs of c-Ha-ras, c-fos, and c-raf-1 revealed little or no expression in AHF. However, the levels of c-myc mRNA were increased in about 10% of the AHF initiated by the highest dose of DEN (200 mg/kg). Thus, altered expression of proto-oncogenes was not seen in AHF initiated by nonnecrogenic doses of DEN and promoted by phenobarbital. However, at the necrogenic dose of 200 mg/kg DEN, c-myc expression was found mostly in AHF in which abnormal expression of GST-P, GGT, G6Pase, and ATPase was also present, indicating that c-myc expression is correlated with phenotypically greater complexity of the AHF, a characteristic of malignant hepatic neoplasms in the rat.
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PMID:Expression of c-myc in altered hepatic foci induced in rats by various single doses of diethylnitrosamine and promotion by 0.05% phenobarbital. 757 7

Changes in intracellular pH (pHin) take part in the mitogenic response. Their importance has been stressed by the finding that mouse fibroblasts expressing a yeast proton pumping ATPase (PMA1) exhibit a transformed phenotype and are tumorigenic. These cells do maintain a higher pHin, supporting the idea that elevated pHin may act as a proliferative trigger. Here we show that cells constitutively expressing PMA1 have higher levels of the AP-1 transcription factor. The use of stable transfectants and transient transfection assays show that PMA1 activity induces transactivation of the c-fos promoter. The activation of the promoter is mediated throughout the serum response element (SRE). The use of protein kinase C inhibitors suggests that AP-1 activation is achieved through a pathway independent of protein kinase C.
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PMID:Activation of the c-fos promoter by increased internal pH. 761 47

Epidermal growth factor (EGF) acutely inhibits acid secretion; however, prolonged administration of EGF has been reported to increase acid production. We undertook these studies to examine whether the physiological effects of EGF on acid secretion are mediated by regulation of gastric H+,K+-ATPase, the principle enzyme responsible for acid secretion. EGF in concentrations equivalent to those in plasma increased H+,K(+)-ATPase alpha-subunit mRNA levels. Using H+,K(+)-ATPase-luciferase constructs transfected into primary cultured parietal cells, a significant step up in EGF inducibility was observed between bases -162 and -156 (5'-GACATGG-3') relative to the cap site. This EGF response element (ERE) conferred EGF inducibility when linked to homologous and heterologous promoters. The ERE is homologous to the 3' half-site of the c-fos serum response element to which rNFIL-6, rE12, and SRE-ZBP bind. Electrophoretic mobility shift assays using an ERE probe and parietal cell nuclear extracts revealed a specific DNA-protein complex, the formation of which was changed by neither E12 and NFIL-6 consensus oligonucleotides nor antibodies for NFIL-6, SRE-ZBP, and E12. Our studies indicate that EGF induces gastric H+,K(+)-ATPase alpha-subunit gene expression via an interaction between a specific ERE and a novel transcriptional factor and that this may be a physiologic mechanism by which EGF regulates acid secretion.
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PMID:Epidermal growth factor induces H+,K+-ATPase alpha-subunit gene expression through an element homologous to the 3' half-site of the c-fos serum response element. 762 93

The SV40 T-antigen-transfected human thyroid cell line SGHTL-34 was used to investigate the effect of thyrotropin (TSH), insulin-like growth factor-1 (IGF-1) and epidermal growth factor (EGF) on c-fos and c-erbB/EGF receptor (EGF-R) mRNA expression and their role in human thyroid cell proliferation. EGF caused a transient 8- and 4-fold increase in c-fos mRNA level after 30 min in serum/hormone-deprived and in logarithmically growing cells, respectively. EGF was only mitogenic in the presence of serum, as measured by 3H-thymidine incorporation and cell counting. TSH had no detectable effect on c-fos mRNA expression and no mitogenic effect on the SGHTL-34 cells. IGF-1 showed no effect alone or in combination with EGF or TSH on either proliferation or c-fos mRNA expression. Our data suggest that increased c-fos mRNA levels are part of the mitogenic pathway, but are insufficient to engender a mitogenic response. SGHTL-34 cells produced high levels of transforming growth factor-alpha (TGF-alpha) and c-erbB/EGF-R mRNA, also seen in thyroid papillary carcinomas. The TGF-alpha protein was detected in conditioned medium from the SGHTL-34 cells, indicating that TGF-alpha may function as an autocrine growth factor. Our data show that the c-erbB/EGF-R mRNA level is regulated by growth factors and hormones in the SGHTL-34 cell line. The SGHTL-34 cells may therefore represent a useful model system for studying the role of TGF-alpha and EGF-R in thyroid carcinogenesis.
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PMID:Growth requirements and oncogene expression in the human thyroid cell line SGHTL-34. 790 43

Teleocidin, a phorbol ester-type tumor promoter, enhanced actin redistribution, vacuole formation and c-fos expression of PLC/PRF/5 hepatoma cells. This tumor promoter also inhibited calcium mobilization induced by epidermal growth factor (EGF). Thapsigargin, a specific inhibitor of endoplasmic reticulum Ca(2+)-ATPase, elevated cytosolic calcium, enhanced c-fos expression and antagonized the vacuole formation induced by teleocidin without interfering with actin redistribution and Lucifer yellow uptake. On the other hand, a calcium ionophore ionomycin elevated both cytosolic Ca2+ and c-fos mRNA but could not antagonize the vacuole formation induced by teleocidin. From these results it was speculated that the Ca2+ leak from the endoplasmic reticulum rather than the elevation of cytosolic Ca2+ appeared to be responsible for the specific inhibition of vacuole formation by thapsigargin.
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PMID:Thapsigargin, an inhibitor of endoplasmic reticulum Ca(2+)-ATPase, enhances c-fos expression but antagonizes vacuole formation of human hepatoma cells induced by teleocidin. 848 67

The calcium ionophore A23187 has been shown to induce the expression of a set of glucose-regulated protein (GRP) genes through the depletion of Ca2+ from the intracellular Ca2+ stores. Here we demonstrate that thapsigargin, which inhibits specifically the endoplasmic reticulum Ca(2+)-ATPase and causes a discharge of the intracellular Ca2+ store, is able to induce the transcription of two grp genes (grp78/BiP and grp94) with kinetics and magnitude similar to that of A23187. The induction of the grp genes by both reagents requires several hours of sustained treatment, in contrast to the rapid induction previously described for c-jun and c-fos. The transactivation of the rat grp78 promoter by A23187 is mediated through sequences spanning -154 to -130 and -99 to -90. Further, simultaneous mutation of two 10-base pair regions, spanning -139 to -130 and -99 to -90, severely reduced the A23187 response. The induction by thapsigargin is also partially mediated through these same promoter elements, without the involvement of the TRE and CRE-like elements of the grp78 promoter. The Ca2+ response elements are further defined by their ability to confer Ca2+ stress inducibility to a heterologous promoter. We show that subdomains of the grp78 promoter are capable of conferring the Ca2+ stress response. In particular, two copies of a 50-base pair region spanning -159 to -110, when cloned in either orientation, can confer a 5- and 9-fold induction by A23187 and thapsigargin, respectively. Our results lend support to the hypothesis that the induction of grp78 by A23187 and thapsigargin following ER Ca2+ discharge acts through a novel pathway in which a Ca2+ signal is transduced through redundant elements containing CCAAT box-like motifs flanked by GC-rich regions.
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PMID:Transactivation of the grp78 promoter by Ca2+ depletion. A comparative analysis with A23187 and the endoplasmic reticulum Ca(2+)-ATPase inhibitor thapsigargin. 850 25

Quiescent cells (in G0) can be stimulated to enter the cell cycle and proceed to DNA synthesis in S-phase by a wide range of growth factors and mitogens. Activation of cell-surface growth factor receptors with intrinsic protein tyrosine kinase activity initiates autophosphorylation of the receptors and subsequent activation of signal transduction cascades. After activation the receptors undergo ligand-induced internalization to endosomes, which become acidified by the action of a vacuolar H(+)-ATPase (V-ATPase). The extent to which vesicular acidification plays a role in mitogenic signalling by receptors with intrinsic tyrosine kinase activity remains unknown. Here we have shown that bafilomycin A1, a specific inhibitor of V-ATPase, inhibits endosome acidification and mitogen-induced DNA synthesis in Swiss 3T3 fibroblasts. Addition of bafilomycin A1 at successively later times during G1 progressively decreased the inhibition of DNA synthesis such that no inhibition was observed when bafilomycin A1 was added at the onset of S-phase. Bafilomycin A1 also induced a dramatic but reversible change in the morphology of Swiss 3T3 cells. However, the rapid activation of c-fos mRNA accumulation by epidermal growth factor and insulin was unaffected by bafilomycin A1. Together, the results suggest that activation of the V-ATPase plays an important role in the mitogenic signalling pathways that occur during the G1 phase of the cell cycle but is not required for the initial epidermal growth factor and insulin-evoked signalling events that lead to c-fos mRNA expression.
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PMID:Inhibition of mitogen-induced DNA synthesis by bafilomycin A1 in Swiss 3T3 fibroblasts. 854 11


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