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:2.7.7.49 (reverse transcriptase)
31,746 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We previously showed that incubation in carbon dioxide (CO2), but not air or helium (He), markedly decreased macrophage intracellular pH (pHi) and resulted in reversible inhibition of lipopolysaccharide- (LPS) stimulated tumor necrosis factor (TNF) and interleukin-1 release. We sought to determine whether carbonic anhydrase inhibition with acetazolamide would prevent CO2-mediated inhibition of LPS-stimulated TNF release. Murine peritoneal macrophages were treated with acetazolamide for 1 h under control atmosphere (95% air/5% CO2) and then switched to incubator modules containing: 1) 80% CO2/20% O2, 2) 80% He/20% O2, or 3) 100% air. Before transfer to experimental atmospheric conditions the macrophages were stimulated with 0 or 1 microg/mL of LPS (Escherichia coli 0111 B4). Supernatant TNF was measured 4 h later by bioassay. In parallel experiments LPS-stimulated cytokine mRNA was estimated using reverse transcriptase polymerase chain reaction (RT-PCR) 2 h after LPS stimulation. Viability was determined using dye uptake. Incubation in CO2 or helium had no effect on TNF production in the absence of LPS. In the absence of acetazolamide CO2 produced marked inhibition of LPS-stimulated TNF release, but this was not blocked by the presence of acetazolamide. This CO2-mediated inhibition of TNF was associated with normal levels of TNF mRNA. In acetazolamide-treated macrophages, LPS resulted in a dose-dependent inhibition of TNF release when the cells were incubated in air or helium. Maintenance of normal intracellular pH is required for TNF release, but not TNF mRNA induction by LPS. Factors that alter intracellular pH regulation may modulate LPS-stimulated cytokine production.
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PMID:Acetazolamide treatment prevents in vitro endotoxin-stimulated tumor necrosis factor release in mouse macrophages. 987 84

Endosymbiotic dinoflagellates resident within cnidarian hosts are extremely productive primary producers. This high productivity may be due in part to an inorganic carbon transport system, present in host tissue, that accelerates carbon delivery to the algae. The enzyme carbonic anhydrase (CA; EC 4.2.1.1) has been shown to be important in this transport system in a variety of tropical symbiotic cnidarians. This study extends the examination of CA to a temperate anemone, Anthopleura elegantissima, and documents symbiosis-enhanced production of CA at the biochemical and molecular level. Depending on light availability, A. elegantissima can occur naturally with (symbiotic) or without (aposymbiotic) dinoflagellates, making it an ideal study organism for symbiosis-enhanced gene expression. We compared (1) CA activities, (2) quantities of CA using an anti-human CA immunoprobe, and (3) quantities of transcript using a semiquantitative PCR in symbiotic versus aposymbiotic A. elegantissima host tissue. Amounts of activity, enzyme, and transcript were greatly enhanced in symbiotic animals compared with aposymbiotic animals. This is the first direct evidence that the presence of symbionts affects the expression of a host cnidarian gene. In addition, we report a full-length A. elegantissima CA cDNA sequence, obtained from subcloned reverse transcriptase-PCR products, and its relatedness to alpha-CAs from a variety of other metazoa, including higher vertebrates.
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PMID:Carbonic anhydrase expression and synthesis in the sea anemone Anthopleura elegantissima are enhanced by the presence of dinoflagellate symbionts. 1022 25

Among more than ten isozymes of the carbonic anhydrase (CA) family, only cytoplasmic CA II and membrane-bound CA IX have been reported to be expressed in human pancreas. To study the mRNA expression of CA isozymes in human pancreas, reverse transcriptase-polymerase chain reaction (RT-PCR)-Southern blot analysis and cDNA sequencing following RT-PCR were employed. CA II, IV, VI, IX, and XII were clearly identified in polyA+ RNA from normal human pancreas by RT-PCR-Southern blotting. Results with cultured pancreatic tumor cell, lines suggest that CA II, IV, IX, and XII are expressed in the ductal cells, and CA VI is expressed in the acinar cells. We propose a hypothesis for the pathophysiological function of CA isozymes in human pancreas; (1) the intraluminal CA isozymes (CA IV, VI, and possibly XII) form a mutually complementary system with cytoplasmic CA II to regulate the luminal pH of the pancreatic duct system and work as a self-defense mechanism against pancreatitis; (2) CA II and other CA isozymes play a pathological role in the autoimmune process of idiopathic chronic pancreatitis.
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PMID:Carbonic anhydrase in human pancreas: hypotheses for the pathophysiological roles of CA isozymes. 1041 46

CA IX is a tumour-associated carbonic anhydrase with proposed roles in pH modulation and intercellular communication. Its distribution was examined in normal, benign and malignant breast tissues and compared with expression of breast tumour markers including oestrogen receptor, c-erbB2, c-erbB3 and CD44. Tissue specimens were analysed using immunohistochemistry and/or reverse transcriptase-polymerase chain reaction (RT-PCR). CA IX was detected by IHC in 12/26 (46%) malignant tissues, 4/36 (11%) benign lesions, but not in 10 normal breasts. Staining was mostly confined to plasma membranes of abnormal epithelial cells, but in five cases was found in adjacent stroma. Semi-quantitative RT-PCR detected CA9 mRNA in 25/39 (64%) malignant tumours, 11/33 (33%) benign lesions, but in none of three normal breasts. Comparative RT-PCR analysis of malignant tissues revealed a relationship between CA9 positivity and c-erbB2 overexpression (p=0.05). Moreover, CA9-positive specimens displayed a significantly higher median level of c-erbB2 than CA9-negative ones (p=0.02). No significant association was found with the other markers. The results of this study support the possible importance of CA IX for breast carcinogenesis and suggest its potential use as a breast tumour marker.
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PMID:Expression of carbonic anhydrase IX in breast is associated with malignant tissues and is related to overexpression of c-erbB2. 1211 77

The sulfonamides constitute an important class of drugs, with several types of pharmacological agents possessing antibacterial, anti- carbonic anhydrase, diuretic, hypoglycemic and antithyroid activity among others. A large number of structurally novel sulfonamide derivatives have ultimately been reported to show substantial antitumor activity in vitro and in vivo. Although they have a common chemical motif of aromatic/heterocyclic or amino acid sulfonamide, there are a variety of mechanisms of their antitumor action, such as carbonic anhydrase inhibition, cell cycle perturbation in the G1 phase, disruption of microtubule assembly, functional suppression of the transcriptional activator NF-Y, and angiogenesis (matrix metalloproteinase, MMP) inhibition among others. Some of these compounds selected via elaborate preclinical screenings or obtained through computer-based drug design, are currently being evaluated in clinical trials. The review summarizes recent classes of sulfonamides and related sulfonyl derivatives disclosed as effective tumor cell growth inhibitors, or for the treatment of different types of cancer. Another research line that progressed much in the last time regards different sulfonamides with remarkable antiviral activity. Thus, at least two clinically used HIV protease inhibitors possess sulfonamide moieties in their molecules, whereas a very large number of other derivatives are constantly being synthesized and evaluated in order to obtain compounds with less toxicity or activity against drug-resistant viruses. Several non nucleoside HIV reverse transcriptase or HIV integrase inhibitors containing sulfonamido groups were also reported. Another approach to inhibit the growth of retroviruses, including HIV, targets the ejection of zinc ions from critical zinc finger viral proteins, which has as a consequence the inhibition of viral replication in the absence of mutations leading to drug resistance phenotypes. Most compounds with antiviral activity possessing this mechanism of action incorporate in their molecules primary sulfonamide groups. Some small molecule chemokine antagonists acting as HIV entry inhibitors also possess sulfonamide functionalities in their scaffold.
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PMID:Anticancer and antiviral sulfonamides. 1267 81

The sulfonamides constitute an important class of drugs, with several types of pharmacological agents possessing antibacterial, anti-carbonic anhydrase, diuretic, hypoglycemic, antithyroid and anticancer activity among others. A large number of structurally novel sulfonamide derivatives have ultimately been reported to show substantial antiviral activity in vitro and in vivo. The review summarizes recent classes of sulfonamides and related sulfonyl derivatives disclosed as effective such agents. Thus, at least some HIV protease inhibitors used clinically (amprenavir) or compounds in advanced clinical trials (tipranavir, TMC-126, TMC-114, etc.) possess sulfonamide moieties in their molecules, whereas a very large number of other derivatives are constantly being synthesized and evaluated in order to obtain compounds with less toxicity or activity against drug-resistant viruses. Several non nucleoside HIV reverse transcriptase or HIV integrase inhibitors containing sulfonamide groups were also reported. Another approach to inhibit the growth of retroviruses, including HIV, targets the ejection of zinc ions from critical zinc finger viral proteins, which has as a consequence the inhibition of viral replication in the absence of mutations leading to drug resistance phenotypes. Most compounds with antiviral activity possessing this mechanism of action incorporate in their molecules primary sulfonamide groups. Finally, some small molecule chemokine antagonists acting as HIV entry inhibitors also possess sulfonamide functionalities in their scaffold.
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PMID:Antiviral sulfonamide derivatives. 1496 91

The mRNA differential display technique was performed to investigate the differences in gene expression in the Longissimus dorsi muscle tissues from LandracexLarge White cross-combination. One novel gene that was differentially expressed was identified using semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) and its complete cDNA sequence was obtained using the rapid amplification of cDNA ends (RACE) method. The nucleotide sequence of the gene is not homologous to any of the known porcine genes. The sequence prediction analysis revealed that the open reading frame of this gene encodes a protein of 260 amino acids that contains the putative conserved domain of the carbonic anhydrase, and this protein has high homology with the carbonic anhydrase III (CA-III) of four species mouse (91%), horse (91%), rat (89%) and human (86%)-so that it can be defined as swine carbonic anhydrase III. The phylogenetic tree analysis revealed that the swine CA-III has a closer genetic relationship with the horse CA-III than with those of mouse, rat and human. The tissue expression analysis indicated that the swine CA-III gene is generally expressed in most tissues. Our experiment is the first to establish the primary foundation for further research on the swine CA-III gene.
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PMID:Isolation, sequence analysis and expression profile of a novel swine gene differentially expressed in the Longissimus dorsi muscle tissues from LandracexLarge white cross-combination. 1575 21

Delays in tissue fixation following tumour vascular clamping and extirpation may adversely affect subsequent protein and mRNA analysis. This study investigated the effect of surgically induced ischaemia in a xenograft model of a colorectal cancer on the expression of a range of prognostic, predictive, and hypoxic markers, with a particular emphasis on thymidylate synthase. Vascular occlusion of human tumour xenografts by D-shaped metal clamps permitted defined periods of tumour ischaemia. Alterations in protein expression were measured by immunohistochemistry and spectral imaging, and changes in mRNA were measured by reverse transcriptase-polymerase chain reaction. Thymidylate synthase expression decreased following vascular occlusion, and this correlated with cyclin A expression. A similar reduction in dihydropyrimidine dehydrogenase was also seen. There were significant changes in the expression of several hypoxic markers, with carbonic anhydrase-9 showing the greatest response. Gene transcriptional levels were also noted to change following tumour clamping. In this xenograft model, surgically induced tumour ischaemia considerably altered the gene expression profiles of several prognostic and hypoxic markers, suggesting that the degree of tumour ischaemia should be minimised prior to tissue fixation.
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PMID:The effect of surgically induced ischaemia on gene expression in a colorectal cancer xenograft model. 1640 65

Marine unicellular coccolithophore algae produce species-specific calcite scales otherwise known as coccoliths. While the coccoliths and their elaborate architecture have attracted the attention of investigators from various scientific disciplines, our knowledge of the underpinnings of the process of biomineralization in this alga is still in its infancy. The processes of calcification and coccolithogenesis are highly regulated and likely to be complex, requiring coordinated expression of many genes and pathways. In this study, we have employed cDNA microarrays to investigate changes in gene expression associated with biomineralization in the most abundant coccolithophorid, Emiliania huxleyi. Expression profiling of cultures grown under calcifying and noncalcifying conditions has been carried out using cDNA microarrays corresponding to approximately 2,300 expressed sequence tags. A total of 127 significantly up- or down-regulated transcripts were identified using a P value of 0.01 and a change of >2.0-fold. Real-time reverse transcriptase PCR was used to test the overall validity of the microarray data, as well as the relevance of many of the proteins predicted to be associated with biomineralization, including a novel gamma-class carbonic anhydrase (A. R. Soto, H. Zheng, D. Shoemaker, J. Rodriguez, B. A. Read, and T. M. Wahlund, Appl. Environ. Microbiol. 72:5500-5511, 2006). Differentially regulated genes include those related to cellular metabolism, ion channels, transport proteins, vesicular trafficking, and cell signaling. The putative function of the vast majority of candidate transcripts could not be defined. Nonetheless, the data described herein represent profiles of the transcription changes associated with biomineralization-related pathways in E. huxleyi and have identified novel and potentially useful targets for more detailed analysis.
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PMID:cDNA microarrays as a tool for identification of biomineralization proteins in the coccolithophorid Emiliania huxleyi (Haptophyta). 1688 5

A combination of protein-ligand docking and ligand-based QSAR approaches has been elaborated, aiming to speed-up the process of virtual screening. In particular, this approach utilizes docking scores generated for already processed compounds to build predictive QSAR models that, in turn, assess hypothetical target binding affinities for yet undocked entries. The "progressive docking" has been tested on drug-like substances from the NCI database that have been docked into several unrelated targets, including human sex hormone binding globulin (SHBG), carbonic anhydrase, corticosteroid-binding globulin, SARS 3C-like protease, and HIV1 reverse transcriptase. We demonstrate that progressive docking can reduce the amount of computations 1.2- to 2.6-fold (when compared to traditional docking), while maintaining 80-99% hit recovery rates. This progressive-docking procedure, therefore, substantially accelerates high throughput screening, especially when using high accuracy (slower) docking approaches and large-sized datasets, and has allowed us to identify several novel potent nonsteroidal SHBG ligands.
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PMID:Progressive docking: a hybrid QSAR/docking approach for accelerating in silico high throughput screening. 1714 75


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