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)

We investigated the effects of calcitonin (CT) and parathyroid hormone (PTH) on the distribution of actin, tubulin, vimentin, and on cell size in cultured chick osteoclasts. In addition, we studied the effects of colchicine on intracellular acidity. Osteoclasts were isolated from the endosteum of 2-3-week chick tibias and were maintained under culture conditions for 5 days. The cells were treated with CT for 30 min or PTH for 60 min and were observed after immunocytochemical staining of cytoskeletal proteins. In untreated cells, actin was found in both a filamentous and a punctate staining pattern, with indented or invaginated regions free of punctate spots. The tubulin distribution in untreated cells was characterized by a pattern of microtubules radiating from the cell center and running parallel to the cell edge. Vimentin staining was usually localized to the perinuclear area. There were no changes in cytoskeletal element distribution or morphology attributable to PTH treatment. Osteoclasts treated with CT were more irregularly shaped, contained more retraction fibers, and were more rounded, with a denser array of cytoskeletal elements in the cell center. In addition, the mean area of the CT-treated cells was significantly less than that of the untreated cells. The actin distribution after CT treatment was still characterized by both a filamentous and a punctate pattern. After CT treatment, vimentin staining appeared more centrally localized than in untreated cells and tubulin staining revealed microtubules which now extended to the retracted cell margin. These results indicate that isolated osteoclasts respond to CT by significant morphological changes which are reflected in the distribution of the major cytoskeletal elements. Disruption of the microtubular system by colchicine treatment also resulted in an initial increase in intracellular acidity, suggesting the involvement of microtubules in the movement of acid-laden vesicles to the exterior.
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PMID:Characterization of the cytoskeleton of isolated chick osteoclasts: effect of calcitonin. 277 8

Past studies of norepinephrine-stimulated protein phosphorylation in intact C-6 glioma cells had identified a 58,000 molecular weight, 5.7 isoelectric point protein (58K-5.7) as a cyclic AMP-dependent phosphoprotein and had shown that 58K-5.7 was one of the most abundant proteins of the nuclear fraction. Initial experiments of present studies showed that the 58K-5.7 protein remained with the nuclear ghost, or matrix structure, after removal of chromatin. Based on the size, acidity, abundance, nonsolubilization by nonionic detergent and salt, and solubilization by urea, the hypothesis was advanced that the 58K-5.7 protein was the vimentin-type intermediate filament protein. The hypothesis was tested by two types of immunochemical experiments. Antisera against hamster vimentin reacted selectively with only the 58K-5.7 protein in polyacrylamide gels of urea-solubilized cellular residues (i.e., nonionic detergent and 0.6 M salt-insoluble material) as determined by immunoautoradiography. Antisera against the pure 58K-5.7 protein of C-6 cells bound selectively to a fibrous array of cellular material typical of vimentin filaments as determined by indirect immunofluorescence. It is concluded that the 58K-5.7 protein is vimentin.
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PMID:Vimentin: a phosphoprotein under hormonal regulation. 702 79

Extracellular acid can have important effects on cancer cells. Acid-sensing ion channels (ASICs), which emerged as key receptors for extracellular acidic pH, are differently expressed during various diseases and have been implicated in underlying pathogenesis. This study reports that ASIC1 and ASIC3 are mainly expressed on membrane of pancreatic cancer cells and upregulated in pancreatic cancer tissues. ASIC1 and ASIC3 are responsible for an acidity-induced inward current, which is required for elevation of intracellular Ca2+ concentration ([Ca2+]i). Inhibition of ASIC1 and ASIC3 with siRNA or pharmacological inhibitor significantly decreased [Ca2+]i and its downstream RhoA during acidity and, thus, suppressed acidity-induced epithelial-mesenchymal transition (EMT) of pancreatic cancer cells. Meanwhile, downregulating [Ca2+]i with calcium chelating agent BAPTA-AM or knockdown of RhoA with siRNA also significantly repressed acidity-induced EMT of pancreatic cancer cells. Significantly, although without obvious effect on proliferation, knockdown of ASIC1 and ASIC3 in pancreatic cancer cells significantly suppresses liver and lung metastasis in xenograft model. In addition, ASIC1 and ASIC3 are positively correlated with expression of mesenchymal marker vimentin, but inversely correlated with epithelial marker E-cadherin in pancreatic cancer cells. In conclusion, this study indicates that ASICs are master regulator of acidity-induced EMT. In addition, the data demonstrate a functional link between ASICs and [Ca2+]i/RhoA pathway, which contributes to the acidity-induced EMT.
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PMID:ASIC1 and ASIC3 contribute to acidity-induced EMT of pancreatic cancer through activating Ca2+/RhoA pathway. 2851 34