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)

Previously, wogonin (5,7-dihydroxy-8-methoxyflavone) was found to suppress proinflammatory enzyme expression including cyclooxygenase-2 (COX-2), contributing to in vivo anti-inflammatory activity against skin inflammation. However, the detailed effect on each skin cell type has not been understood. Therefore, present investigation was carried out to find the effect of wogonin on inflammation associated gene expression from skin fibroblasts in culture using reverse transcriptase-polymerase chain reaction. As a result, it was found that wogonin (10-100 microM) clearly down-regulated COX-2 expression from NIH/3T3 cells treated with 12-O-tetradecanoylphorbol 13-acetate, interleukin-1beta or tumor necrosis factor-alpha. But, the expression levels of COX-1, interleukin-1beta and fibronectin were not significantly affected. This finding was well correlated with significant reduction of prostaglandin E2 (PGE2) production by wogonin. As a comparison, NS-398 (selective cyclooxygenase 2 inhibitor) did not suppress COX-2 expression and other gene levels, while PGE2 production was potently reduced at 0.1-10 microM. All these results suggest that COX-2 down-regulation of skin fibroblasts may be, at least in part, one of anti-inflammatory mechanisms of wogonin against skin inflammation.
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PMID:Suppression of cyclooxygenase-2 expression of skin fibroblasts by wogonin, a plant flavone from Scutellaria radix. 1558

Transforming growth factor-beta1 is known for its effect on the production of extracellular matrix in tendons. Elevated levels of transforming growth factor-beta1 have been reported in tendon adhesion and tendinosis, which suggests that transforming growth factor-beta1 plays an important role in matrix disturbances. Tendon adhesion involves excessive collagen deposition, whereas tendinosis is associated with increased proteoglycan deposition. It seems that other factors also may affect matrix deposition and modulate the effects of transforming growth factor-beta1. We assessed whether matrix anchorage to Type I collagen or fibronectin could change the gene expression of matrix proteins in tendon fibroblasts, and studied whether the effects of transforming growth factor-beta1 were altered by matrix anchorage. Human patellar tendon fibroblast cultures were prepared in different cell anchorages, and the cellular responses to transforming growth factor-beta1 were measured as gene expression of procollagen Type I, Type III, decorin, and biglycan by real-time reverse transcriptase-polymerase chain reaction. Fibronectin anchorage significantly increased the messenger ribonucleic acid level of decorin, and the messenger ribonucleic acid level of procollagen Type I was decreased by matrix anchorage to either fibronectin or Type I collagen. Transforming growth factor-beta1 increased the messenger ribonucleic acid level of procollagen Type I in Type I collagen-coated plates, but it suppressed the messenger ribonucleic acid level of decorin in fibronectin-coated plates. These findings suggest that interaction of matrix anchorage and transforming growth factor-beta1 is an important determinant of matrix deposition in healing tendons and the development of matrix disturbances in tendons.
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PMID:TGF-beta1 reverses the effects of matrix anchorage on the gene expression of decorin and procollagen type I in tendon fibroblasts. 1568 80

Cells can sense the physical and chemical properties of artificial materials used as scaffolds for tissue engineering and regulate their behavior. Therefore, biomimetic and biospecific molecules are coated on materials to regulate function of cells on the tissue-engineered product. These bioactive molecules can be attached in a defined spectrum, concentration and spatial distribution in order to control adhesion, growth, viability, differentiation, and function of the cells. When autologous cells are used for tissue engineering, initially limited cells obtained may often need an amplification of cell number by passage in tissue culture before they are seeded on a biomaterial or scaffold. We have conducted this study to understand how the characteristics of bioactive molecule coating might affect proliferation, apoptosis and differentiation when endothelial cell (EC) is serially passaged. Proliferation was assessed by proliferating cell nuclear antigen (PCNA) staining along with counting of cells harvested from confluent monolayer. Apoptosis was assessed by Annexin V staining and differentiation by semi quantitative reverse transcriptase polymerase chain reaction (RT-PCR) for von Willebrand factor (vWF) expression and quantification of its release using enzyme linked immunosorbant assay (ELISA), and thrombogenicity by comparing platelet adhesion to EC monolayer Dacron grafts (DG) with specific protein coating. The results indicate that ECs easily lose its proliferation potential when they are cultured repeatedly on gelatin, turn apoptotic and over express the prothrombotic protein- vWF. Whereas, when it is grown on a matrix composed of fibrin, fibronectin, gelatin and vascular EC growth factor (VEGF), the cells retained their ability to proliferate, remained viable and were relatively less thrombogenic, even when passage number progressed. It is concluded that if ECs are grown on the composite matrix that mimics natural vessel scaffold, the cell number can be amplified without affecting its normal physiological function and may be used to generate effective tissue-engineered cardiovascular constructs.
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PMID:Effect of passage number and matrix characteristics on differentiation of endothelial cells cultured for tissue engineering. 1587 71

Maspin is a mammary serine protease inhibitor or serpin with tumor suppressive and antiangiogenic activity that inhibits tumor motility, invasion and metastasis, at least by its actions on cell membrane and extracellular matrix (ECM) proteins. Previous studies documented that the quinazoline-derived alpha1-adrenoceptor antagonist doxazosin affects the attachment and migration of prostate cancer cells. In this study, we investigated the effect of maspin overexpression on the apoptotic/antiadhesion response of prostate cancer cells to doxazosin. The response of maspin-overexpressing clones of human prostate cancer cells DU-145 to doxazosin was evaluated by determining cell viability, apoptosis and cell proliferation on the basis of the trypan blue exclusion assay/methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay, Hoechst staining and caspase-3 activation, and [(3)H]thymidine incorporation assay. Vascular endothelial growth factor (VEGF), transforming growth factor betaRII (TGFbetaRII), Smad4 (a TGFbeta intracellular effector) and bax expression was evaluated at the mRNA and protein level using reverse transcriptase-polymerase chain reaction and Western blotting, respectively. The effect of doxazosin on cell attachment of maspin-expressing prostate cancer cells was evaluated on collagen- and fibronectin-coated plates. Cell migration was assessed using the wounding assay. In response to tumor necrosis factor-related apoptosis-inducing ligand, DU-145-maspin expressing cells undergo apoptosis, via poly(ADP-ribose) polymerasecleavage and caspase-3 activation. DU-145-maspin cells exhibited higher sensitivity to doxazosin and an earlier temporal activation of caspase-3. The number of apoptotic cells detected in response to doxazosin was significantly higher compared to the neo control (P<0.0001). Doxazosin resulted in dramatic downregulation of the 189 isoform of VEGF in maspin transfectants, while a fivefold induction of Smad4 mRNA expression was detected in those cells after 24 h of treatment. Maspin overexpression in prostate cancer cells resulted in an increased ability to attach to ECM-coated plates, and doxazosin treatment considerably antagonized this effect by decreasing the attachment potential to collagen and fibronectin. The present study supports the ability of maspin to enhance the apoptotic threshold of prostate cancer cells to the quinazoline-based alpha1-adrenoceptor antagonist doxazosin. These findings may have therapeutic significance in the development of antiangiogenic targeting by doxazosin and derivative agents for advanced prostate cancer.
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PMID:Maspin sensitizes prostate cancer cells to doxazosin-induced apoptosis. 1600 19

Fibronectin (FN), a matrix glycoprotein, has been shown to undergo alternative splicing exclusively during organogenesis and tumorigenesis. One such splice variant, extradomain-B (ED-B) FN, is normally absent in normal adult tissues and is proposed to be a marker of tumoral angiogenesis. The present study was aimed at elucidating whether ED-B FN is expressed in non-small cell lung carcinomas and whether such aberrant expression correlates with tumoral angiogenesis. Frozen tissues from 28 non-small cell lung carcinomas (consisting of both squamous cell carcinomas and adenocarcinomas) along with paired normal tissue samples were collected from the tissue bank collection of the Department of Pathology, London Health Sciences Center, Canada. Frozen tissue specimens were subjected to RNA extraction and real time reverse transcriptase-polymerase chain reaction (RT-PCR) with respect to total and ED-B FN isoform expression. In addition, paraffin-embedded tissue sections from the same cases were collected for histological analysis using ED-B FN antibody. Tumor tissues were further stained with CD34 antibody and analyzed semiquantitatively for tumor microvessel density. The results demonstrate up-regulation of ED-B FN mRNA levels in lung tumor tissues as compared to paired normal tissues. Furthermore, ED-B FN expression was localized specifically to tumor cells and was found to correlate with tumor microvessel density. These findings provide evidence of possible involvement of ED-B FN in pulmonary tumoral angiogenesis. Furthermore, ED-B FN may potentially be used as a diagnostic marker and a target for antiangiogenic therapy.
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PMID:ED-B fibronectin in non-small cell lung carcinoma. 1620 24

Two-dimensional thin films consisting of homopolymer and discrete compositional blends of tyrosine-derived polycarbonates were prepared and characterized in an effort to elucidate the nature of different cell responses that were measured in vitro. The structurally similar blends were found to phase separate after annealing with domain sizes dependent on the overall composition. The thin polymer films were characterized with the use of atomic force microscopy (AFM), water contact angles, and time-of-flight secondary ion mass spectrometry (TOF-SIMS) and significant changes in roughness were measured following the annealing process. Genetic expression profiles of interleukin-1beta and fibronectin in MC3T3-E1 osteoblasts and RAW 264.7 murine macrophages were measured at several time points, demonstrating the time and composition-dependent nature of the cell responses. Real-time reverse transcriptase polymerase chain reaction (RT-PCR) depicted upregulation of the fibronectin gene copy numbers in each of the blends relative to the homopolymers. Moreover, the interleukin-1beta expression profile was found to be compositionally dependent. The data suggest strongly that optimal composition and processing conditions can significantly affect the acute inflammatory and extracellular matrix production responses.
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PMID:Cellular response to phase-separated blends of tyrosine-derived polycarbonates. 1627 65

Bone marrow angiogenesis plays an important role in the pathogenesis and progression in multiple myeloma. Recent studies have shown that proteasome inhibitor bortezomib (Velcade, formerly PS-341) can overcome conventional drug resistance in vitro and in vivo; however, its antiangiogenic activity in the bone marrow milieu has not yet been defined. In the present study, we examined the effects of bortezomib on the angiogenic phenotype of multiple myeloma patient-derived endothelial cells (MMEC). At clinically achievable concentrations, bortezomib inhibited the proliferation of MMECs and human umbilical vein endothelial cells in a dose-dependent and time-dependent manner. In functional assays of angiogenesis, including chemotaxis, adhesion to fibronectin, capillary formation on Matrigel, and chick embryo chorioallantoic membrane assay, bortezomib induced a dose-dependent inhibition of angiogenesis. Importantly, binding of MM.1S cells to MMECs triggered multiple myeloma cell proliferation, which was also abrogated by bortezomib in a dose-dependent fashion. Bortezomib triggered a dose-dependent inhibition of vascular endothelial growth factor (VEGF) and interleukin-6 (IL-6) secretion by the MMECs, and reverse transcriptase-PCR confirmed drug-related down-regulation of VEGF, IL-6, insulin-like growth factor-I, Angiopoietin 1 (Ang1), and Ang2 transcription. These data, therefore, delineate the mechanisms of the antiangiogenic effects of bortezomib on multiple myeloma cells in the bone marrow milieu.
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PMID:Bortezomib mediates antiangiogenesis in multiple myeloma via direct and indirect effects on endothelial cells. 1639 31

DEC-205 (CD205) belongs to the macrophage mannose receptor family of C-type lectin endocytic receptors and behaves as an antigen uptake/processing receptor for dendritic cells (DC). To investigate DEC-205 tissue distribution in human leukocytes, we generated a series of anti-human DEC-205 monoclonal antibodies (MMRI-5, 6 and 7), which recognized epitopes within the C-type lectin-like domains 1 and 2, and the MMRI-7 immunoprecipitated a single approximately 200 kDa band, identified as DEC-205 by mass spectrometry. MMRI-7 and another DEC-205 mAb (MG38), which recognized the epitope within the DEC-205 cysteine-rich and fibronectin type II domain, were used to examine DEC-205 expression by human leukocytes. Unlike mouse DEC-205, which is reported to have predominant expression on DC, human DEC-205 was detected by flow cytometry at relatively high levels on myeloid blood DC and monocytes, at moderate levels on B lymphocytes and at low levels on NK cells, plasmacytoid blood DC and T lymphocytes. MMRI-7 F(ab')2 also labeled monocytes, B lymphocytes and NK cells similarly excluding reactivity due to non-specific binding of the mAb to FcgammaR. Tonsil mononuclear cells showed a similar distribution of DEC-205 staining on the leukocytes. DEC-205-specific semiquantitative immunoprecipitation/western blot and quantitative reverse transcriptase-PCR analysis established that these leukocyte populations expressed DEC-205 protein and the cognate mRNA. Thus, human DEC-205 is expressed on more leukocyte populations than that were previously assumed based on mouse DEC-205 tissue localization studies. The broader DEC-205 tissue expression in man is relevant to clinical DC targeting strategies and DEC-205 functional studies.
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PMID:Expression of human DEC-205 (CD205) multilectin receptor on leukocytes. 1658 22

We used cDNA microarrays to study gene expression in fresh frozen papillary thyroid carcinoma (PTC) specimens. Seven clinically aggressive carcinomas were included, comprising poorly differentiated PTC and tumors with extensive local invasion or synchronous distant metastases. Ten differentiated (classic) papillary thyroid carcinomas (PTC) and non-neoplastic thyroid tissues were also investigated. TaqMan quantitative reverse transcriptase-polymerase chain reaction (RT-PCR), in situ hybridization, and immunohistochemistry verified the differential gene expression. The B-Raf gene was mutated with a T-->A transversion at nucleotide 1799 (V600E) in 8 of 10 differentiated PTC, and in 4 of 7 aggressive carcinomas. Among genes markedly and equally over-expressed in carcinomas of both the aggressive and classic PtC groups, compared to normal thyroid tissue, were CBP/p300 transactivator (CItED1), fibronectin, growth/differentiation factor 15, potassium inwardly rectifying channel KCNJ2, glutaminyl peptide cyclotransferase, WNT7A, and dipeptidyl peptidase IV. A marked upregulation in carcinomas of P-cadherin mRNA and protein concomitant with E-cadherin downregulation, indicates a possible P-E cadherin "switch" in PTC. The growth factor homologue Nel-like 2, dual specificity phosphatase 5, the serine protease kallikrein 10, and also the tight junction genes claudin 1 and claudin 16, were upregulated in classic PTC but not in aggressive tumors, which may be consistent with altered cell polarity in the dedifferentiated PtC. The aggressive, poorly differentiated PtC group was specifically characterized by marked upregulation of several genes related to cell proliferation such as cell division cycle 2 (CDC2), CDC7, kinesin-like 5, ubiquitin conjugating enzyme E2C, and topoisomerase IIalpha, and by upregulation of genes encoding extracellular matrix proteins such as seprase, extracellular matrix protein 1, and several collagens. These aggressive tumors were also characterized by overexpression of the integrin ligand periostin, and in some biopsies also of osteopontin and of the upstream Rac-regulator dedicator of cytokinesis 10 (DOCK10). These data are interpreted to be consistent with altered cell motility, extracellular matrix remodeling and increased cell proliferation, as important processes in PTC tumor progression.
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PMID:Gene expression in poorly differentiated papillary thyroid carcinomas. 1667 2

Staphylococcus aureus is a major human and animal pathogen. During infection, this organism not only is able to attach to and enter host cells by using its cell surface-associated factors but also exports toxins to induce apoptosis and kill invaded cells. In this study, we identified the regulon of a two-component signal transduction system, SaeRS, and demonstrated that the SaeRS system is required for S. aureus to cause infection both in vitro and in vivo. Using microarray and real-time reverse transcriptase PCR analyses, we found that SaeRS regulates the expression of genes involved in adhesion and invasion (such as those encoding fibronectin-binding proteins and fibrinogen-binding proteins) and genes encoding alpha-, beta-, and gamma-hemolysins. Surprisingly, we found that SaeRS represses the Agr regulatory system since the mutation of saeS up-regulates agrA expression, which was confirmed by using an agr promoter-reporter fusion system. More importantly, we demonstrated that inactivation of the SaeRS system significantly decreases the bacterium-induced apoptosis and/or death of lung epithelial cells (A549) and attenuates virulence in a murine infection model. Moreover, we found that inactivation of the SaeRS system eliminates staphylococcal adhesion and internalization of lung epithelial cells. We also found that both a novel hypothetical protein (the SA1000 protein) and a bifunctional protein (Efb), which binds to extracellular fibrinogen and complement factor C3, might partially contribute to bacterial adhesion to and invasion of epithelial cells. Our results indicate that activation of the SaeRS system may be required for S. aureus to adhere to and invade epithelial cells.
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PMID:Inactivation of a two-component signal transduction system, SaeRS, eliminates adherence and attenuates virulence of Staphylococcus aureus. 1686 53


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