Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.27.5 (RNase)
 17,967 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Secretin is an important regulator of pancreatic function, but the molecular basis of its actions is not well understood. We have, therefore, used in situ autoradiography, photoaffinity labeling, and RNase protection assays with healthy rat pancreas, dispersed acinar cells, and pancreas depleted of acinar cells to explore the cellular distribution and molecular identity of high-affinity secretin receptors in this complex organ. The autoradiographic examination of 125I-labeled [Tyr10]rat secretin-27 binding to normal pancreas demonstrated saturable and specific high-affinity binding sites on both acinar and duct cells, with a uniform lobular distribution, but with no binding above background over islets or vascular structures. Photoaffinity labeling demonstrated that the ductular binding site in acinar cell-depleted copper-deficient rat pancreas represented the same glycoprotein with a molecular weight of 50,000-62,000 that was present on acinar cells. RNase protection assays confirmed the molecular identity of the secretin receptors expressed on these distinct cells. The apparent absence or extreme low density of similar secretin receptors on islets and pancreatic vascular structures suggests that the pharmacological effects of secretin on those cells may either be indirect or mediated by another secretin family receptor that recognizes this hormone with lower affinity.
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PMID:Cellular distribution of secretin receptor expression in rat pancreas. 984 82

We recently reported that secretin induces the exocytic insertion of functional aquaporin-1 water channels (AQP1) into the apical membrane of cholangiocytes and proposed that this was a key process in ductal bile secretion. Because AQP1 is present on the basolateral cholangiocyte membrane in low amounts, we hypothesized that another AQP must be expressed at this domain to facilitate transbasolateral water movement. Thus, we investigated the expression, subcellular localization, possible regulation by secretin, and functional activity of AQP4, a mercury-insensitive water channel expressed in other fluid transporting epithelia. Using reverse transcription-polymerase chain reaction (RT-PCR) on RNA prepared from purified rat cholangiocytes, we amplified a product of 311 bp that was 100% homologous to the reported AQP4 sequence. RNase protection assay confirmed the presence of an appropriate size transcript for AQP4 in cholangiocytes. Immunoblotting detected a band of approximately 31 kd corresponding to AQP4 in basolateral but not apical membranes of cholangiocytes. Secretin did not alter the amount of plasma membrane AQP4 but, as expected, induced AQP1 redistribution from intracellular to apical plasma membranes. Functional studies showed that AQP4 accounts for about 15% of total cholangiocyte membrane water permeability. Our results indicate that: (1) cholangiocytes express AQP4 messenger RNA (mRNA) and protein and (2) in contrast to AQP1, which is targeted to the apical cholangiocyte membrane by secretin, AQP4 is constitutively expressed on the basolateral cholangiocyte membrane and is secretin unresponsive. The data suggest that AQP4 facilitates the basolateral transport of water in cholangiocytes, a process that could be relevant to ductal bile formation.
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PMID:Expression of aquaporin-4 water channels in rat cholangiocytes. 1082 57

Legionella pneumophila, the gram-negative agent of Legionnaires' disease, possesses type IV pili and a type II protein secretion (Lsp) system, both of which are dependent upon the PilD prepilin peptidase. By analyzing multiple pilD mutants and various types of Lsp mutants as well as performing trans-complementation of these mutants, we have confirmed that PilD and type II secretion genes are required for L. pneumophila infection of both amoebae and human macrophages. Based upon a complete analysis of lspDE, lspF, and lspG mutants, we found that the type II system controls the secretion of protease, RNase, lipase, phospholipase A, phospholipase C, lysophospholipase A, and tartrate-sensitive and tartrate-resistant acid phosphatase activities and influences the appearance of colonies. Examination of the developing L. pneumophila genome database indicated that the organism has two other loci (lspC and lspLM) that are predicted to promote secretion and thus a set of genes that is comparable to the type II secretion genes in other gram-negative bacteria. In contrast to lsp mutants, L. pneumophila pilus mutants lacking either the PilQ secretin, the PspA pseudopilin, or pilin were not defective for colonial growth, secreted activities, or intracellular replication. L. pneumophila dot/icm mutants were also not impaired for type II-dependent exoenzymes. Upon intratracheal inoculation into A/J mice, lspDE, lspF, and pilD mutants, but not pilus mutants, exhibited a reduced ability to grow in the lung, as measured by competition assays. The lspF mutant was also defective in an in vivo kinetic assay. Examination of infected mouse sera revealed that type II secreted proteins are expressed in vivo. Thus, the L. pneumophila Lsp system is a virulence factor and the only type II secretion system linked to intracellular infection.
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PMID:Legionella pneumophila type II protein secretion promotes virulence in the A/J mouse model of Legionnaires' disease pneumonia. 1468 10

Telomerase, which ensures the unlimited proliferation by adding TTAGGG repeat at the end of the chromosome, is strongly activated at a very high incidence in a variety of malignant neoplasms including pancreatic cancer. In addition to the acquisition of the immortality, telomerase plays an important role in the aggressive behavior of pancreatic cancer. Invasiveness of human pancreatic cancer cells correlates well with telomerase activity. Exposure of pancreatic cancer to anticancer drugs up-regulates telomerase activity, and the increase in telomerase activity correlates with resistance to the drug-induced apoptosis. More important, diagnositic values of telomerase activity are highly focused because of the lack of other specific genetic markers for pancreatic cancer. Samples of pancreatic juice are obtained at endoscopic retrograde pancreatography using a balloon catheter after intraveneous injection of secretin. Because the pancreatic juice has strong protease and RNase activity, addition of protease inhibitors and RNase inhibitors in the telomerase extraction buffer is necessary for the detection of telomerase activity in the pancreatic juice. A telomeric ladder was detected in 80% patients with carcinoma, whereas only 4.3% patients with adenoma and none with chronic pancreatitis showed positive telomerase activity.
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PMID:Detection of telomerase activity in patients with pancreatic cancer. 1554 8


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