Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0847097 (acidity)
 15,165 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Small GTPase RhoA regulates signal transduction from receptors in the membrane to a variety of cellular events related to cell morphology, motility, cytoskeletal dynamics, cytokinesis, and tumour progression, but it is unclear how RhoA regulates intracellular membrane dynamics of lysosomes. We showed previously by confocal immunofluorescence microscopy that the transfection of dominant active RhoA in MM1 cells causes the dispersal translocation of lysosomes stained for cathepsin D throughout the cytoplasm. Y-27632, a selective inhibitor of p160ROCK, impeded the cellular redistribution of lysosomes and promoted reclustering of lysosomes toward the perinuclear region. Here we have further investigated whether the acidic lysosomal vesicles dispersed throughout the cytoplasm are applied to the early endosomes in the endocytic pathway, and we demonstrate that the dispersed lysosomes were accessible to endocytosed molecule such as dextran, and their acidity was not changed, as determined by increased accumulation of the acidotropic probe LysoTracker Red. Brefeldin A did not induce the tabulation of these dispersed lysosomes, but it caused early endosomes to form an extensive tubular network. The dispersed lysosomes associated with cathepsin D and LIMPII were not colocalized with early endosomes, and these vesicles were not inaccessible to the endocytosed anti-transferrin receptor antibody. Moreover, wortmannin, an inhibitor of phosphatidylinositol 3-kinase, induced a dramatic change in LIMPII-containing structures in which LIMPII-positive swollen large vacuoles were increased and small punctate structures disappeared in the cytoplasm. These swollen vacuoles were not doubly positive for LIMPII and transferrin receptor, and were not inaccessible to the internalized anti-transferrin receptor antibody. Therefore, our novel findings presented in this paper indicate that RhoA activity causes a selective translocation of lysosomes without perturbing the machinery of endocytic pathway.
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PMID:A role for small GTPase RhoA in regulating intracellular membrane traffic of lysosomes in invasive rat hepatoma cells. 1258 97

Escherichia coli survives pH 2 acid stress at a level rivalling Helicobacter pylori. Of the three E. coli acid resistance systems involved, the one most efficient and most studied uses isozymes of glutamate decarboxylase (GadA/GadB) to consume intracellular protons, and a glutamate:gamma-amino butyric acid (GABA) anti-porter (GadC) to expel GABA in exchange for extracellular glutamate. Because acid resistance is a critical factor in resisting stomach acidity, mechanisms that control this system are extremely important. Here we show that an Era-like, molecular switch GTPase called TrmE regulates glutamate-dependent acid resistance. Western blot analysis revealed a TrmE-dependent, glucose-induced system and a TrmE-independent, glucose-repressed pathway. Gene fusion studies indicated that the TrmE requirement for GadA/B production takes place at both the transcriptional and translational levels. TrmE controls GAD transcription by affecting the expression of GadE, the essential activator of the gadA and gadBC genes. TrmE most probably controls gadE expression indirectly by influencing the synthesis or activity of an unknown regulator that binds the gadE control region. Translational control of GAD production by TrmE appears to be more direct, affecting synthesis of the decarboxylase and the anti-porter proteins. TrmE GTPase activity was critical for both the transcriptional and translational effects. Thus, TrmE is part of an increasingly complex control network designed to integrate diverse physiological signals and forecast future exposures to extreme acid. The significance of this network extends beyond acid resistance as the target of this control, GadE, regulates numerous genes in addition to gadA/BC.
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PMID:The Era-like GTPase TrmE conditionally activates gadE and glutamate-dependent acid resistance in Escherichia coli. 1552 79

Gastric acidity-associated disorders such as peptic ulcer and reflux diseases are widespread, and the reported resistance and side effects of currently used medicines suggest an urgent requirement for alternative therapeutic approaches. Here we demonstrate a critical role of ASAP3 in regulating the microvilli structure of parietal cells in vivo, and reveal the feasibility of controlling gastric acidity by targeting ASAP3. Conditional knockout of ASAP3 in mice caused elongation and stacking of microvilli in parietal cells, and substantially decreased gastric acid secretion. These were associated with active assembly of F-actin caused by a higher level of GTP-bound Arf6 GTPase. Consistently, a small molecular compound QS11 inhibited ASAP3 function and significantly reduced gastric acidity in vivo. Of note, the expression of ASAP3 was positively correlated with gastric acid secretion in 90 human cases, and high expression of ASAP3 was associated with reflux disease and peptic ulcer. These results reveal for the first time that ASAP3 regulates the microvilli structures in parietal cells. Our data also suggest ASAP3 as a feasible and drugable therapeutic target for gastric acidity-associated diseases.
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PMID:ASAP3 regulates microvilli structure in parietal cells and presents intervention target for gastric acidity. 2926 12