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)

This study was designed to detect apoptosis in both human senile cataracts and cataracts associated with diabetic retinopathy (DR) and to elucidate the signaling pathway involved in its regulation. Samples of human cataracts were obtained from 56 patients (senile cataracts, n = 40; cataracts with DR, n = 16) and were analyzed by the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) method, transmission electron microscopy, immunohistochemistry, and reverse transcriptase-polymerase chain reaction (RT-PCR) assay of apoptotic modulators. The TUNEL study demonstrated that the percentage of TUNEL-positive cells in the cataracts with proliferative DR was higher than in the senile cataracts ( P < 0.05). The immunohistochemistry and RT-PCR assay showed a higher level of Fas expression and Fas mRNA in the cataracts with DR than in the senile cataracts, although there was no difference in the expression level of the Fas ligand, Bcl-2, and their mRNAs between both groups. The number of dark cells, which were characterized by a convoluted nucleus and chromatin condensation with abundant free 3'-OH DNA ends, was higher in the cataracts with DR than in the senile cataracts ( P < 0.01). Apoptosis plays an important role in the development of cataracts with DR, but not in senile cataracts, and may be induced by Fas-mediated signaling.
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PMID:Fas-mediated apoptosis in human lens epithelial cells of cataracts associated with diabetic retinopathy. 1265 58

Nelarabine, prodrug of arabinosylguanine (ara-G), has demonstrated T-lymphoblastic antileukemic activity in cell lines and in the clinic. To investigate the mechanism for lineage-specific toxicity, the effects of ara-G were compared in CEM (T-lymphoblast), Raji (B-lymphoblast), and ML-1 (myeloid) cell lines. CEM cells were the most sensitive to ara-G-induced apoptosis and accumulated the highest levels of ara-G triphosphate (ara-GTP). However, compared with myeloid and B-lineage cell lines, CEM cells incorporated fewer ara-G molecules-which were at internucleotide positions in all 3 cell lines- into DNA. Ara-G induced an S-phase arrest in both Raji and ML-1, while in CEM the S-phase cells decreased with a concomitant increase in the sub-G1 population. Within 3 hours of ara-G treatment, the levels of soluble Fas ligand (sFasL) in the medium increased significantly in CEM cultures. In parallel, an induction of FasL gene expression was observed by real-time reverse transcriptase-polymerase chain reaction (RT-PCR). Pretreatment of CEM cells with a Fas antagonistic antibody inhibited ara-G-mediated cell death. These results demonstrate that high ara-GTP accumulation in T cells results in an S phase-dependent apoptosis induced by ara-G incorporation into DNA, which may lead to a T cell-specific signal for the induction and liberation of sFasL. Subsequently, the sFasL induces an apoptotic response in neighboring non-S-phase cells. In contrast, myeloid and B cells accumulated lower levels of ara-GTP and arrested in S phase, blocking any apoptotic signaling.
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PMID:Mechanisms for T-cell selective cytotoxicity of arabinosylguanine. 1275 Jan 68

The Fas ligand (FasL) pathway is one of the two major effector mechanisms of T-cell-mediated cell death. FasL expression by extralymphatic tissues is thought to maintain a status of immunity. Accordingly, it has been proposed that tumor cells express FasL as a mechanism of immunologic escape. However, data regarding FasL expression in normal or neoplastic tissues remain controversial. In the present study, we investigated the expression of FasL in normal peripheral blood B lymphocytes or malignant cells of the B-lymphocyte lineage to elucidate a possible immunologic counterattack mechanism. FasL gene expression was analyzed by reverse transcriptase polymerase chain reaction in two non-Hodgkin's lymphoma (NHL) entities: the highly aggressive Burkitt's lymphoma (BL) and indolent NHL chronic lymphocytic leukemia (CLL). FasL expression was found to be consistently negative in all BL cell lines and purified samples from patients with CLL. FasL is not constitutively expressed in normal peripheral blood or neoplastic B lymphocytes making the Fas counterattack, as described for gastrointestinal cancer, unlikely as a mechanism of immunologic escape of lymphoma cells.
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PMID:Fas ligand is not constitutively expressed in low-grade B-cell lymphoma and B-lymphoblastoid cells. 1293 Mar 19

It is well known that lymphocytes play a major role in coronary plaque destabilization in acute coronary syndromes. The aim of this study was to evaluate circulating lymphocyte apoptosis in patients with non-ST elevation myocardial infarction (NSTEMI) in comparison with subjects with stable angina and with healthy controls. We considered spontaneous lymphomonocyte apoptosis (evaluated by ELISA), interleukin (IL)-2 production (evaluated by ELISA), Fas expression on T cells (evaluated by flow cytometry) and Fas ligand mRNA (evaluated by reverse transcriptase polymerase chain reaction), as well as Fas functionality. To evaluate T-cell activation, we also investigated T-cell subpopulations (CD4/CD8 ratio), T-cell surface HLA-DR and CD69 expression (evaluated by flow cytometry) in blood taken within 6 hours from onset of NSTEMI. Spontaneous apoptosis was significantly increased in NSTEMI patients in comparison with the two control groups and it was associated with an increased expression of Fas, an increased susceptibility to the Fas agonist (CH-11) and a normal production of IL-2 in cell cultures. We also found a significant increase of HLA-DR+ CD3+ and CD69+ CD4+ cells in NSTEMI patients. These data suggest that the enhanced apoptosis is due to a mechanism of "active" antigen-driven death, induced by the expression of death cytokines and not by the failure of cell growth factors. We conclude that in case of NSTEMI peripheral lymphocytes are activated and undergo an enhanced programmed cell death due to activation mechanisms. It is likely that lymphocyte activation occurs before the onset of acute ischemia and contributes to the plaque rupture and to the myocardial ischemic insult.
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PMID:[Lymphocyte apoptosis in non-ST segment elevation acute myocardial infarction ]. 1462 21

To examine the usefulness of interleukin-18 (IL-18) in the treatment of osteosarcomas, the effect of IL-18 on the growth of Dunn osteosarcoma cells was investigated. Daily intraperitoneal (i.p.) injection of mouse recombinant IL-18 (2 microg/mouse) suppressed the growth of Dunn osteosarcoma cells transplanted subcutaneously (s.c.) into syngeneic C3H mice. This IL-18-induced suppression was not affected by simultaneous treatment with anti-asialo GM1 serum, which inactivates natural killer (NK) cells. However, IL-18 failed to suppress the growth of Dunn osteosarcoma cells transplanted into BALB/c-nude mice devoid of T lymphocytes or C3H-gld/gld mice deficient in functional Fas ligand (FasL). IL-18 also failed to suppress the growth of Dunn osteosarcoma cells in vitro, although expression of IL-18 receptor mRNA and MyD88 mRNA as well as Fas mRNA was detected by reverse transcriptase-polymerase chain reaction (RT-PCR). On the other hand, antimouse Fas antibody showed cytotoxicity against Dunn osteosarcoma cells in a dose-dependent manner in vitro. In addition, treatment of C3H mice with IL-18 enhanced the cytotoxic activity of CD8(+) T lymphocytes against Dunn osteosarcoma cells. These results indicate that IL-18 inhibits the growth of Dunn osteosarcoma cells in vivo by enhancing the cytotoxic activity of CD8(+) T lymphocytes through the FasL-Fas system.
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PMID:Inhibition by interleukin-18 of the growth of Dunn osteosarcoma cells. 1503 49

Extracellular nucleotides are stress-responsive ligands that mediate a variety of cellular processes via purinoceptors. We hypothesized that mechanical ventilation (MV) would alter the extracellular adenyl-nucleotide profile and purinoceptor expression in lung and extrapulmonary tissues. Twenty-eight rats were randomized to: (i) unventilated control animals; (ii) tidal volume (VT; 6 ml/kg); (iii) VT (6 ml/kg) and positive end-expiratory pressure (PEEP; 5 cm H20); (iv) VT (12 ml/kg); or (v) VT (12 ml/kg) and PEEP (5 cm H20). Bronchoalveolar lavage (BAL) was analyzed for adenyl-nucleotides. Pulmonary, hepatic, and renal tissues were assessed for P2Y4, P2Y6, P2X7, A3, and A2b receptor expression by real-time reverse transcriptase-polymerase chain reaction and Fas/Fas ligand mRNA was quantified in the lung. MV produced volume-dependent changes in BAL nucleotides; AMP and adenosine increased, whereas ATP and ADP proportions decreased. Large-volume MV increased A2b mRNA and decreased P2X7 in the lung; mRNA changes in lung Fas ligand paralleled P2X7. PEEP normalized BAL nucleotide profiles and A2b expression. Injurious MV reduced hepatic and renal P2X7 mRNA; PEEP normalized these levels in both tissues. Large-volume MV also decreased renal A2b mRNA. MV alters the BAL adenyl-nucleotide profile and purinoceptor patterns in lung, liver, and kidney. PEEP normalizes the BAL nucleotide profile and receptor patterns in lung and extrapulmonary tissues.
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PMID:Mechanical ventilation alters airway nucleotides and purinoceptors in lung and extrapulmonary organs. 1538 14

Nitric oxide (NO) derived from inducible NO synthase has been implicated in cardiac rejection. However, little is known about the role of the reactive nitrogen species peroxynitrite. We examined the protective actions of a peroxynitrite decomposition catalyst, WW85, in an experimental model of acute cardiac rejection. Heterotopic, abdominal transplantation of rat donor hearts was performed. Groups included isografts, allografts, or allografts treated with WW85, cyclosporine, or cyclosporine + WW85. We determined graft survival, histological rejection, and graft function (by in situ sonomicrometry). Intragraft biochemical analysis of cytokines and proapoptotic and antiapoptotic gene expression using reverse transcriptase-polymerase chain reaction were determined. Treatment with WW85 or cyclosporine alone prolonged graft survival, improved graft function, and decreased histological rejection. Graft survival was further significantly (P < 0.001) enhanced by combination treatment. A decrease was also shown in nitrotyrosine, poly(ADP-ribose) polymerase (PARP) activation, and lipid peroxide formation by WW85 that was potentiated when given in combination with cyclosporine. Benefits could not be ascribed to changes in intragraft myeloperoxidase activity. Only combination therapy produced significant decreases in inflammatory cytokine gene expression, suggesting that WW85 acted primarily downstream of these stimuli. In general, WW85 had no direct action on expression of the proapoptotic gene, Fas ligand; however, WW85 given alone or with cyclosporine enhanced expression of antiapoptotic genes Bcl-2 and Bcl-xL. Collectively, these findings suggest a protective action of the peroxynitrite decomposition catalyst WW85 on graft rejection that is independent of any action on leukocyte sequestration and cytokine gene expression. Rather, effects seem to be downstream on decreased protein nitration, decreased lipid peroxidation, and decreased PARP activation.
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PMID:Protective mechanisms of a metalloporphyrinic peroxynitrite decomposition catalyst, WW85, in rat cardiac transplants. 1578 53

TNF-related apoptosis-inducing ligand (TRAIL), as well as Fas ligand, plays a pivotal role in lymphocyte cytotoxicity and the maintenance of immunological homeostasis in various tissues, but its physiological role in immune evasion of cancer cells remains unknown. We have previously shown strong resistance to TRAIL-induced cytotoxicity in human hepatocellular carcinomas (HCCs). The current study investigates the expression of TRAIL in HCCs. We found that three HCC cells, HepG2, Hep3B and Huh7 cells, constitutively express TRAIL mRNA and protein, as detected by reverse transcriptase PCR and Western blotting. Four of 10 human HCC tissues demonstrated positive staining for TRAIL, whereas non-tumor tissues showed little detectable staining. TRAIL expression on tumor cells was detected by flow cytometry and was dramatically induced after the addition of doxorubicin, a chemotherapeutic agent, or cytokine stimulation with TNF-alpha, IL-1beta or IL-18. This expression was induced principally via the NF-kappaB activation pathway, since IkappaB transfection significantly reduced TRAIL expression. In addition, the expressed TRAIL was functional. The TRAIL on HCC cells induced apoptosis in Jurkat cells that are sensitive to TRAIL-mediated apoptosis, and this process was specifically inhibited by recombinant TRAIL-receptors:Fc which binds to TRAIL. In conclusion, TRAIL expressed on the surface of HCC cells by cytokines or cytostatic drugs might contribute to an alternative mechanism that enables tumors to evade immune surveillance by inducing apoptosis of activated human lymphocytes.
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PMID:Expression of TNF-related apoptosis-inducing ligand in human hepatocellular carcinoma. 1580 18

Apoptosis mediated by the Fas/Fas ligand (FasL) has been implicated in rejection of solid organ allografts and it has been recently proposed that soluble forms of Fas could interfere with this interaction, blocking apoptosis. The purpose of this study was to analyze intragraft Fas, FasL, and soluble Fas mRNA levels in relation to acute rejection in cardiac allografts in humans. mRNA levels were determined by quantitative reverse transcriptase-polymerase chain reaction in 42 samples of endomyocardial biopsies obtained from 18 cardiac transplant recipients within the first 6 months after transplantation. FasL and Fas mRNA levels were higher in biopsies with rejection than in biopsies without rejection, and no difference was observed in soluble Fas mRNA. During rejection, there was a positive correlation between the mRNA levels of Fas-FasL, Fas-soluble Fas, and FasL-soluble Fas. During quiescent periods, however, the only correlation observed was between Fas and soluble Fas mRNA levels. In conclusion, our findings do not suggest a role for soluble Fas, confirm the heightened expression of FasL, and indicate, for the first time, an increased expression of Fas in acute rejection of cardiac allografts.
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PMID:Expression of Fas, FasL, and soluble Fas mRNA in endomyocardial biopsies of human cardiac allografts. 1669 21

Endothelin (ET)-1 is an autocrine/paracrine growth factor or an antiapoptotic factor in human cancers, and blockade of ET-1 receptors can sensitize human tumor cells to apoptosis. The role of the ET-1 axis in the proliferation and/or apoptosis of melanoma cells and in their response to the alkylating agent, dacarbazine (DTIC), used in clinical treatment of human melanoma were investigated in five human melanoma cell lines obtained form surgical resection specimens. Melanoma cells expressed the messenger RNAs (mRNAs) for the components of the ET-1 axis. ET-1 binding was mediated by ET(B) but was inhomogeneous among melanoma cells. Exogenous ET-1 did not induce human melanoma cell proliferation. Bosentan, a dual ET(A/B)-receptor antagonist, decreased melanoma cell viability and DNA synthesis and induced melanoma cell apoptosis in defined human melanoma cells. Bosentan potentiated Fas ligand-induced apoptosis only in one melanoma cell line. Variants of ET(B)were determined using reverse transcriptase (RT) polymerase chain reaction (PCR) and primers spanning the whole sequence of the ET(B)gene. ET(B)variants were demonstrated only in one of the five cell lines, corresponding to the absence of ET-1 binding by these cells. Bosentan did not inhibit the effects of alkylating agents, and the effects of bosentan and alkylating agents were additive in melanoma cells. In conclusion, exogenous ET-1 is not a growth factor for human melanoma cells, but blockade of ET receptors decreases proliferation, induces apoptosis, and potentiates the effects of anticancer agents in defined melanoma cells, suggesting that combination therapy of ET-receptor antagonists with alkylating agents may improve their efficacy.
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PMID:Targeting the endothelin axis in human melanoma: combination of endothelin receptor antagonism and alkylating agents. 1674 Oct 59


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