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

---

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

The activated sludge process relies on the formation of strong microbial flocs. The knowledge about dominant floc-forming bacteria is at present very limited, especially from a phylogenetic perspective. In this study, numerous microcolonies in the activated sludge flocs were found to be targeted by a Betaproteobacteria-group-specific oligonucleotide probe using fluorescence in situ hybridization (FISH). Some of these were micromanipulated and further identified by reverse transcriptase polymerase chain reaction (RT-PCR) and sequencing to belong to the Aquaspirillum genus in the Neisseriaceae family. A specific oligonucleotide probe, Aqs997, was designed to target the identified bacteria. A survey in nine different wastewater treatment plants with nutrient removal (WWTP) showed a high abundance of bacteria hybridizing to the oligonucleotide probe developed. Microautoradiography (MAR) combined with FISH on activated sludge incubated with radiolabelled substrate showed uptake of substrate with oxygen, nitrate and nitrite as electron acceptor demonstrating a denitrifying potential of the bacteria investigated. The Aquaspirillum-related bacteria seemed to be abundant denitrifiers in WWTPs with nitrogen removal and they were particularly numerous in plants mainly receiving domestic wastewater, where they constituted up to 30% of all bacteria.
...
PMID:Micromanipulation and further identification of FISH-labelled microcolonies of a dominant denitrifying bacterium in activated sludge. 1504 20

In malignant tumors the balance of matrix metalloproteinases (MMP) and tissue inhibitors of matrix metalloproteinases (TIMP) is disturbed. Radical oxygen species (ROS) and hydrogen peroxide potentially influence this balance. Therefore, we analyzed the balance of MMP and TIMP in renal cell carcinoma (RCC) specimens and cell lines. In RCC specimens MMP-2, MMP-9, TIMP-1, and TIMP-2 were immunohistochemically detected. Tumor-associated macrophages (TAM) as a potential source of ROS were characterized with an anti-CD68 antibody. Three RCC cell lines were treated with sublethal concentrations of hydrogen peroxide to simulate the effects of radical oxygen species. MMP-2 and MMP-9 protein expression was measured by zymography. mRNA expression of MMP-2, MMP-9, TIMP-1, and TIMP-2 was assessed by quantitative reverse transcriptase polymerase chain reaction. Tumor cell-derived reactive oxygen species were measured by FACS analysis and dihydrorhodamine 123 oxidation. In RCCs the MMP and TIMP expression profile was variable. The balance between MMP and TIMP was shifted towards MMP in comparison to matched normal controls. TAM were localized in a close vicinity to MMP expresssing tumor cells. As in RCC specimens, the expression of MMP and TIMP in the analyzed RCC cell lines varied. Hydrogen peroxide induced MMP-2 and -9 mRNA and protein expression, whereas TIMP-1 and TIMP-2 mRNA levels remained unaffected in cell lines. Thus, the ratio between MMP and TIMP was shifted towards MMP. Tumor cells did not increase the production of reactive oxygen species stimulation with phorbol ester or hydrogen peroxide. In RCC the balance between MMP and TIMP is disturbed. Oxidative stress potentially increases this imbalance. TAM might be one source of hydrogen peroxide thus supporting the invasive properties of RCCs.
...
PMID:The balance between MMP-2/-9 and TIMP-1/-2 is shifted towards MMP in renal cell carcinomas and can be further disturbed by hydrogen peroxide. 1506 27

We present a review of the current status of the use of methylene blue (MB) photoinactivation of viruses starting with the first early observations up to its current use to inactivate HIV-1 in blood products. Basic mechanism of action studies conducted with model bacteriophages indicate that MB-photomediated viral RNA-protein crosslinkage is a primary lesion and that oxygen, specifically singlet oxygen, is very important also. Basic studies on the mechanism of action with HIV are lacking; however, we do show new data illustrating that viral reverse transcriptase inactivation per se cannot account for MB-mediated photoinactivation. We also show data illustrating that MB photomediates the inactivation of West Nile Virus, a flavivirus, which poses a significant new threat to the continental US. MB photoinactivation of viruses show significant promise because the technology not only offers significant potency but the history of safe MB use in human therapy makes it attractive also.
...
PMID:Methylene blue photoinactivation of RNA viruses. 1516 94

Hypoxia is a characteristic feature of many human pathologies, including cancer. The sustained proliferation rate of tumor cells leads to alterations of the tumor microenvironment, that progressively becomes more acidic, nutrient-deprived, and hypoxic. The reduced partial pressure of oxygen triggers the onset of an adaptive response, aimed at increasing the local oxygen concentration by several complementary actions. Although directly exposed to the blood stream, endothelial cells lining the vascular lumen in tumors also can be exposed to hypoxia and therefore can contribute to the onset of the adaptive response that leads to tumor angiogenesis. Aiming at getting a detailed insight into the oxygen-dependent regulation of the transcriptional program of vascular endothelial cells and at identifying new relevant markers that may be used as targets for therapeutic intervention in tumor angiogenesis, we have performed a broad-range transcriptomic analysis, using the Affymetrix HG-U133A Gene Chips, of mRNA expression levels in human umbilical cord vein endothelial cells (HUVEC), exposed in vitro to hypoxia for different time periods. The transcriptomic analysis was complemented by a semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR) analysis of mRNA levels and alternative splicing for some selected extracellular matrix protein genes, and by a proteomic analysis, using two-dimensional polyacrylamide gel electrophoresis (2-D PAGE) and tandem mass spectrometry for protein separation and identification, of hypoxic and normoxic HUVEC whole-cell lysates and subcellular fractions. Our analysis confirmed previous findings on genes whose expression is regulated by oxygen concentration but also identified new genes (e.g., CXCR4, claudin 3, CD24, tetranectin, Del-1, procollagen lysyl hydroxylase 1 and 2) which are transcriptionally upregulated in hypoxic conditions.
...
PMID:Modulation of gene expression by hypoxia in human umbilical cord vein endothelial cells: A transcriptomic and proteomic study. 1517 42

The mutation and resultant adaptability of HIV-1 reverse transcriptase (RT) present a major challenge to the design of the effective antiviral strategies because many initially potent drugs lose efficacy over time. Even though there is an urgent need for a comprehensive understanding of the molecular mechanism of anti-HIV drug resistance by mutant RTs, the unavailability of the structural information of the mutant RTs has prevented detailed investigations. In this study, the active site of the 3TC-resistant (M184V) RT is constructed by a computational method, which clearly shows that the side chain of Val184 occupies the binding site for the nucleoside triphosphates. Therefore, the distance between the side chain of Val184 and the sugar moiety of the nucleoside triphosphate must be closely related to the cross-resistance by M184V RT. The natural substrates, 2'-deoxyribo nucleoside triphosphates, escape from the steric stress from the bulky side chain of Val184 by virtue of the d-sugar conformation as well as the interaction of its 3'-OH group with Tyr115, which locates the nucleoside triphosphate out of the clashing distance from Val184. Similarly, the energy-minimized structures of various d-dioxolane nucleoside triphosphates (TP)/RT complexes indicate that the d-dioxolane sugar moiety acquires enough distance from Val184 due to the specific interaction of its 3'-oxygen atom with the nearby enzyme residues such as Tyr115 and Arg72.
...
PMID:Molecular mechanism of dioxolane nucleosides against 3TC resistant M184V mutant HIV. 1519 15

Our previous study demonstrated that polycationic liposomes are highly stable in the bloodstream and represent an effective agent for liver gene delivery. We report here that liposome-mediated extracellular superoxide dismutase (EC-SOD) gene delivery successfully prevented acute liver injury in mice. The therapeutic efficacy of EC-SOD gene delivery by polycationic liposomes was determined against the toxicity of superoxide anions and hydroxyethyl radicals in HepG2 cells and in a mouse model of acute liver injury caused by D-galactosamine and lipopolysaccharide intoxication. Transfection of HepG2 cells with an EC-SOD plasmid led to a striking increase in superoxide dismutase activity in the medium. The transfected cells had much less cell death after reactive oxygen species exposure compared with untransfected or control plasmid-transfected cells. In a model of acute liver injury, serum alanine aminotransferase levels in mice receiving portal vein injections of EC-SOD lipoplexes were much lower than in those receiving normal saline, liposomes alone, or control lipoplexes. Liver histology confirmed that there was less cell death in the EC-SOD lipoplex-treated group. Quantitative reverse transcriptase polymerase chain reaction showed a 55-fold increase in human EC-SOD gene expression in the liver of mice injected with EC-SOD lipoplexes. Serum superoxide dismutase activity in EC-SOD lipoplex-treated mice was higher than in the control groups; this was associated with higher liver glutathione levels and reduced lipid peroxidation. In conclusion, polycationic liposome-mediated EC-SOD gene delivery protects against reactive oxygen species toxicity in vitro and against lipopolysaccharide-induced acute liver injury in D-galactosamine-sensitized mice.
...
PMID:Liposome-mediated extracellular superoxide dismutase gene delivery protects against acute liver injury in mice. 1523 3

The toxicity of nucleoside reverse transcriptase inhibitors (NRTIs) is linked to altered mitochondrial DNA (mtDNA) replication and subsequent disruption of cellular energetics. This manifests clinically as elevated concentrations of lactate in plasma. The mechanism(s) underlying how the changes in mtDNA replication lead to lactic acidosis remains unclear. It is hypothesized that mitochondrial oxidative stress links the changes in mtDNA replication to mitochondrial dysfunction and ensuing NRTIs toxicity. To test this hypothesis, changes in mitochondrial function, mtDNA amplification efficiency, and oxidative stress were assessed in HepG2-cultured human hepatoblasts treated with the NRTI stavudine (2',3'-didehydro-2',3'-deoxythymidine or d4T) for 48 h. d4T produced significant mitochondrial dysfunction with a 1.5-fold increase in cellular lactate to pyruvate ratios. In addition, d4T caused a dose-dependent decrease in mtDNA amplification and a correlative increase in abundance of markers of mitochondrial oxidative stress. Manganese (III) meso-tetrakis (4-benzoic acid) porphyrin, MnTBAP, a catalytic antioxidant, ameliorated or reversed d4T-induced changes in cell injury, energetics, mtDNA amplification, and mitochondrial oxidative stress. In conclusion, d4T treatment elevates mitochondrial reactive oxygen species (ROS), enhances mitochondrial oxidative stress, and contributes mechanistically to NRTI-induced toxicity. These deleterious events may be potentiated in acquired immunodeficiency syndrome (AIDS) by human immunodeficiency virus (HIV) infection itself, coinfection (e.g., viral hepatitis), aging, substance, and alcohol use.
...
PMID:Mitochondrial oxidative stress in human hepatoma cells exposed to stavudine. 1528 86

Pulmonary arterial hypertension (PAH) is a progressive disease of the pulmonary vasculature involving endothelial and vascular smooth muscle cell (VSMC) proliferation, vasoconstriction, right ventricular hypertrophy, and eventually, right heart failure and death. PAH occurs 1000-fold more frequently in HIV patients than in the general population. Although conventional HIV therapy with nucleoside reverse transcriptase inhibitors (NRTIs) leads to regression of PAH, highly active antiretroviral therapy (HAART; two NRTI plus a protease inhibitor) increases the incidence of HIV-associated PAH as much as twofold. Although there are relatively few models for PAH, previous reports indicate the disease can be initiated by endothelial injury and release of the mitogen endothelin-1 (ET-1). ET-1, in turn, stimulates VSMC proliferation. To determine whether HAART induces endothelial injury and release of cytokines like ET-1, we treated human umbilical vein endothelial cells with micromolar amounts of AZT (3'-azido-3'-deoxythymidine), the protease inhibitor indinavir, or AZT plus indinavir, and measured cell viability, mitochondrial function, and ET-1 release. Both AZT and indinavir induced marked decreases in cellular oxygen uptake, as well as increases in ET-1 release. Although the drugs had no apparent effect on proliferation in VSMCs alone, in cocultures of VSMCs plus endothelial cells, the drugs increased proliferation of both endothelial cells and VSMCs. Finally, when cocultures of endothelial cells and VSMCs were treated with BQ-123 and BQ-788, selective antagonists for ET(A) and ET(B) receptors, respectively, drug-induced proliferation of both VSMCs and endothelial cells was attenuated. These data thus suggest that HIV drug cocktails may exacerbate preexisting HIV-associated PAH by inducing endothelial mitochondrial dysfunction, in turn stimulating the release of ET-1, and ultimately, vascular cell proliferation.
...
PMID:Effects of HIV drug combinations on endothelin-1 and vascular cell proliferation. 1537 29

Highly active antiretroviral therapy (HAART) has significantly improved the prognosis of HIV-1-infected patients but is associated with significant side effects such as diabetes, atherosclerosis, and cardiovascular complications. Oxidative stress can disrupt endothelial homeostasis by dysregulating the balance between pro- and antiatherogenic factors. We hypothesized that chronic exposure to HAART results in endothelial oxidative stress and activation of mononuclear cell recruitment, an early event in atherosclerosis. We studied the effects of HAART drug combinations, consisting of zidovudine, a nucleoside reverse transcriptase inhibitor; efavirenz, a nonnucleoside reverse transcriptase inhibitor; and either of the two protease inhibitors (PIs), indinavir or nelfinavir, on human aortic endothelial cells (HAECs) by monitoring the following parameters: (1) generation of reactive oxygen species (ROS), (2) mono-nuclear cell (Jurkat or U-937) adhesion, and (3) expression of cell adhesion molecules (CAMs). HAART exposure increased ROS formation in HAECs. Exposure to PIs alone and in HAART combinations increased mononuclear cell adhesion to HAECs in a concentration-dependent manner. Mononuclear cell adhesion to HAART-exposed HAECs was significantly enhanced following acute (24-h) exposure to the inflammatory cytokines, tumor necrosis factor (TNF)-alpha or interleukin (IL)-1beta and was suppressed by the antioxidants N-ace-tylcysteine and glutathione. Exposure to HAART increased intercellular adhesion molecule-1 (ICAM-1) gene expression and concomitant exposure to TNF-alpha further increased ICAM-1, vascular cell adhesion molecule-1 (VCAM-1), and endothelial-leukocyte adhesion molecule cell surface protein levels. These studies indicate that chronic HAART exposure increases oxidative stress in endothelial cells and induces mononuclear cell recruitment, which may eventually precipitate the cardiovascular diseases observed in HIV-1+ individuals on antiretroviral therapy.
...
PMID:HAART drugs induce oxidative stress in human endothelial cells and increase endothelial recruitment of mononuclear cells: exacerbation by inflammatory cytokines and amelioration by antioxidants. 1547 Feb 76

For the last ten years, antiretroviral therapy (ARV) has improved the prognosis in HIV-1 infection and showed a better control of the viral excretion by reducing viral shedding in semen. However, nucleoside analogues reverse transcriptase inhibitors (NRTI) therapy reported important adverse effects. Most of these side effects observed seem to be linked with a common mechanism: mitochondrial activity alteration. Since the introduction of protocols for HIV-1 serodiscordant couples, with male infected partners under NRTI therapy, many results in the literature such as: semen characteristics and pregnancies, drew the attention of research teams. Many studies have suggested that NRTI has an affect on semen parameters, but proposed mechanisms of these effects have rarely been discussed. NRTI have a great affinity for the reverse transcriptase of HIV-1. Because many NRTI are not only inhibitors of reverse transcriptase but also inhibitors of the DNA polymerase beta and gamma, several toxic effects can be considered. Nevertheless, this specificity is not absolute and "accidental" incorporations of NRTI can occur on genomic sperm DNA. Only one study on genomic sperm DNA with patients under NRTI therapy was published without concluding results. Recently, studies have suggested that NRTI exposure could induce an alteration on mitochondrial energy-generating ability of spermatozoa. NRTI are known to induce an increase in the generation of reactive oxygen species, which results in the degradation of mitochondrial transmembrane potential (Deltapsim). This loss of Deltapsim can tend to release some specific apoptosis factors, such as cytochrome c, that initiates programmed cell death. Sperm DNA fragmentation, associated to apoptosis, was reported as a possible cause of recurrent pregnancy loss. If the incorporation of NRTI was reported in genomic DNA of somatic cells, the absence of data on the genomic sperm DNA justifies further studies concerning the effects of paternal exposure to NRTI on the genomic material of the male gamete, in particular because of its implication in the zygote development after fertilization.
...
PMID:[Impact of reverse transcriptase inhibitors on sperm mitochondrial and genomic DNA in assisted reproduction techniques]. 1550 Nov 59


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>

---