Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.7.49 (reverse transcriptase)
 31,746 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cyclopentenone prostaglandins (PGs) inhibit virus replication in several DNA and RNA virus models, in vitro and in vivo. In the present report we demonstrate that the cyclopentenone prostaglandins PGA(1) and PGJ(2) at nontoxic concentrations can dramatically suppress HIV-1 replication during acute infection in CEM-SS cells. PGs did not affect HIV-1 adsorption, penetration, reverse transcriptase activity nor viral DNA accumulation in HIV-1 infected cells. A dramatic reduction in HIV-1 mRNA levels was detected up to 48-72 h after infection (p.i.) in PG-treated cells, and HIV-1 protein synthesis was greatly reduced by a single PG-treatment up to 96 h p.i. Repeated PGA(1)-treatments were effective in protecting CEM-SS cells by the cytopathic effect of the virus, and in dramatically reducing HIV-1 RNA levels up to 7 d after infection. The antiviral effect was not mediated by alterations in the expression of alpha-, beta-, or gamma-interferon,TNFalpha, TNFbeta, IL6, and IL10 in HIV-infected CEM-SS cells. The fact that prostaglandins are used clinically in the treatment of several diseases, suggests a potential use of cyclopentenone PGs in the treatment of HIV-infection.
 ...
PMID:Inhibition of HIV-1 replication by cyclopentenone prostaglandins in acutely infected human cells. Evidence for a transcriptional block. 862 62

Folate-binding protein (FBP) was identified and characterized in a pig liver cDNA library by screening with a 0.6 kb fragment from the cDNA of FBP from a human KB cell cancer line. The cDNA of pig liver FBP included 1230 bp containing 759 bp in the open reading frame with 80% similarity to the human placenta FBP. The deduced 253 amino acid sequence showed 67-73% similarity to previous sequences and contained 16 conserved cysteine residues, 11 tryptophan potential folate-binding sites, three sites for N-linked glycosylation and 14 hydrophobic C-terminal residues. Northern analysis and reverse transcriptase PCR identified transcripts in pig liver and kidney, but not in jejunal mucosa. Although defining the molecular structure of pig liver FBP, these studies suggest that this protein participates in the regulation of folate uptake by liver and kidney membranes but is not involved in folate absorption.
 ...
PMID:Folate binding protein: molecular characterization and transcript distribution in pig liver, kidney and jejunum. 892 Sep 73

Previous studies have demonstrated that cyclopentenone prostaglandins (cyPG) inhibit human immunodeficiency virus type 1 (HIV-1) replication in various cell types. We investigated the role of PG in the replication of HIV-1 in primary macrophages. The cyPG, PGA(1) and PGA(2), inhibited HIV-1 replication in acutely infected human monocyte-derived macrophages (MDM). Because PGA(1) and PGA(2) have previously been shown to be peroxisome proliferator-activated receptor gamma (PPARgamma) agonists, we examined the effect of synthetic PPARgamma agonists on HIV replication. The PPARgamma agonist ciglitazone inhibited HIV-1 replication in a dose-dependent manner in acutely infected human MDM. In addition, cyPG and ciglitazone reduced HIV replication in latently infected and viral entry-independent U1 cells, suggesting an effect at the level of HIV gene expression. Ciglitazone also suppressed HIV-1 mRNA levels as measured by reverse transcriptase PCR, in parallel with the decrease in reverse transcriptase activity. Co-transfection of PPARgamma wild type vectors and treatment with PPARgamma agonists inhibited HIV-1 promoter activity in U937 cells. Activation of PPARgamma also decreased HIV-1 mRNA stability following actinomycin D treatment. In summary, our experimental findings implicate PPARgamma as an important factor in the suppression of HIV-1 gene expression in MDM by cyPG. Thus natural and synthetic PPARgamma agonists may play a role in controlling HIV-1 infection in macrophages.
 ...
PMID:Peroxisome proliferator-activated receptor gamma agonists inhibit HIV-1 replication in macrophages by transcriptional and post-transcriptional effects. 1184 31

The role of L- and D-isomers of homocysteine (Hcy) in vascular versus endocardial endothelial (EE) remodeling and function is not well understood. The hypothesis is that Hcy decreases EE cell density by activating matrix metalloproteinase (MMP) and by inducing left ventricular hypertrophy (LVH) in homocysteinemic hypertensive rats (HHR). And L- and D-isomers of Hcy have differential effects in vessel and myocardium. We used: 1) spontaneously hypertensive rats (SHR) in which endogenous total homocyst(e)ine (tHcy) levels are moderately high (18 micromol/L); 2) control age- and sex-matched normotensive Wistar rats (NWR) in which tHcy levels are normal (4 micromol/L); to create hyperhomocyst(e)inemia, 32 mg/day Hcy was administered for 12 weeks in 3) SHR (SHR-H), and in 4) NWR (NWR-H) rats; 5) endogenous tHcy levels were reduced (from 18 to 12 micromol/L) in SHR by folic acid administration (SHR-F). Plasma tHcy levels were measured by HPLC and spectrophometric methods. The MMP activity, measured by zymography, is increased by chronic Hcy administration, and folic acid treatment decreases MMP activity. The collagen and transforming growth factor-beta1 (TGF-beta1), measured by reverse transcriptase-polymerase chain reaction, are increased by Hcy. Folic acid treatment decreases collagen expression and increases TGF-beta1. In vivo LV function was measured in anesthetized rats by a catheter in the left ventricle. The partial decrease in tHcy levels and no change in arterial pressure in SHR after folic acid administration, suggested that folic acid decreases one of the L- or D-isomer of Hcy, which is not responsible for an increase in arterial pressure, but may be responsible for myocardial dysfunction. The chronic Hcy administration decreases EE function in NWR and SHR. The treatment of folic acid in SHR improves LVH and EE function. Folic acid improves cardiac remodeling and EE function by decreasing one of the D- or L-isomer of Hcy and by decreasing MMP activity in HHR. These results may suggest a differential role of L- and D-isomers in vascular versus cardiac remodeling.
 ...
PMID:Reversal of endocardial endothelial dysfunction by folic acid in homocysteinemic hypertensive rats. 1186 51

Glutathione (GSH) synthesis is differentially regulated in the embryo and visceral yolk sac (VYS) of the developing rat conceptus. The innate capacity to respond to environmental insult and chemical exposure by inducing de novo GSH synthesis may help to determine overall cell sensitivity and/or resistance to chemically induced malformation. Specific activities of glutamate-cysteine ligase (GCL), the rate limiting enzyme in GSH synthesis, were determined by measuring the formation of gamma-glutamylcysteine (GC) in homogenates prepared from rat embryos and VYSs. GC formation increased linearly with time and with relative protein concentration. Specific activities were found to be 60.5 +/- 3.2 and 118.9 +/- 4.2 pmol GC/mg protein/min in the gestational day (GD) 10 embryo and VYS, respectively, and 22.7 +/- 0.4 and 71.3 +/- 0.6 pmoles GC/mg protein/min in the respective GD 11 embryo and VYS. Apparent kinetic constants determined from embryo and VYS homogenates gave respective apparent K(m) values for glutamate of 0.75 and 1.38 mM and for cysteine 0.03 mM in both tissues. Apparent V(max) values were higher in the VYS in each case, corresponding with a lower apparent K(m) and higher GCL activity. GCL specific activities increased significantly following a 24 h in vitro exposure to diethyl maleate (DEM) and diamide, but remained unchanged following exposure to prostaglandin A(2) (PGA(2)) and t-butylated hydroxytoluene (BHT). Basal expression of GCL catalytic subunit (GCL(C)) and regulatory subunit (GCL(R)) was 59- and 25-fold higher in VYS, respectively, compared to the embryo. Quantitative real-time fluorescence reverse transcriptase polymerase chain reaction (RT-PCR) showed that following DEM and diamide treatment, GCL(C) expression increased up to 19-fold in embryonic tissues but was not induced in the VYS. Only DEM increased the expression of the light/regulatory subunit GCL(R) in the embryo (8-fold). Densitometry of immunoblots revealed approximately 75% more GCL(C) in the VYS than in the embryo. Following treatments, a marked increase was induced in embryonic GCL(C) content with both DEM (85%) and diamide (19%), but in the VYS, only DEM caused an increase in GCL(C) protein (38%).
 ...
PMID:Spatial activities and induction of glutamate-cysteine ligase (GCL) in the postimplantation rat embryo and visceral yolk sac. 1511 89

DL-alpha-Lipoic acid (LPA) was reported to be effective in reducing free radicals generated by oxidative stress. The protective of effect of LPA on methanol (MeOH) induced free radical changes and oxidative damages in discrete regions of rat brain have been reported in this study. Folate deficient rat (FDD) model was used. The five animal groups (saline control, FDD control, FDD+MeOH, FDD+LPA+MeOH, LPA control) were used. The FDD+MeOH and FDD+LPA+MeOH animals were injected intraperitoneally with methanol (3gm/kg). After 24h, the level of free radical scavengers such as, superoxide dismutase, catalase, glutathione peroxidase, reduced glutathione was estimated in six discrete regions of brain, retina and optic nerve. Level of protein thiol, protein carbonyl and lipid peroxidation was also estimated. Expression of heat shock protein 70 mRNA (hsp70) was studied in the cerebellum and hippocampus by reverse transcriptase PCR. All the samples showed elevation in the level of free radical scavenging enzymes and reduced level of glutathione in the FDD+MeOH group in relation to the other groups. hsp70 expression was more in FDD+MeOH group when compared to FDD+LPA+MeOH group. In conclusion, MeOH exposure leads to increased free radical generation and protein oxidative damages in the rat nervous tissue. Treatment with LPA prevents oxidative damage induced by MeOH exposure.
 ...
PMID:Efficacy of DL-alpha-lipoic acid on methanol induced free radical changes, protein oxidative damages and hsp70 expression in folate deficient rat nervous tissue. 1739 94

Escherichia coli contains a four-gene operon, pgaABCD, which encodes the proteins necessary for the synthesis of polymeric N-acetylglucosamine, or PGA. Poly-N-acetyl-glucosamine was first described in Staphylococcus aureus and Staphylococcus epidermidis and was found to have important roles in biofilm formation and immune evasion. PGA also plays a role in biofilm formation in E. coli, but its role in immune evasion has not been thoroughly studied. We previously reported that E. coli PGA cross-reacts with an opsonic-antibody raised against S. aureus PNAG and this is the basis for an ongoing investigation regarding the development of a vaccine against both pathogens. In this paper we investigated pga expression in wild type and csrA or nhaR deletion mutant strains during different growth phases and temperatures, and in response to chemical stimuli using a pga promoter-reporter fusion construct, real-time reverse transcriptase-PCR, immunoblotting, and biofilm assays. Expression of pga and polysaccharide synthesis were induced by glucose, NaCl, and ethanol, but only glucose augmented biofilm formation. The regulatory factor NhaR was required for NaCl-induced pga expression, whereas the effects of glucose and ethanol were independent of CsrA and NhaR.
 ...
PMID:Effect of growth conditions on poly-N-acetylglucosamine expression and biofilm formation in Escherichia coli. 1844 67

Poly(gamma-glutamic acid) (gamma-PGA) nanoparticles (NPs) have previously been reported as an efficient antigen delivery system with adjuvant activity. In this study, the gene expression in murine bone marrow-derived dendritic cells (DCs) treated with gamma-PGA NPs was examined by oligonucleotide microarray analysis and compared with that in cells treated with other adjuvants. The gene expression of proinflammatory chemokines, cytokines, and costimulatory molecules was upregulated considerably in DCs treated with gamma-PGA NPs. The upregulation pattern was similar to that in DCs treated with lipopolysaccharide (LPS) but not to that in DCs treated with unparticulate gamma-PGA. The activation of DCs by gamma-PGA NPs was confirmed by real-time reverse transcriptase PCR (RT-PCR) analysis of genes related to Toll-like receptor (TLR) signaling. The effect of gamma-PGA NPs on DCs was not annihilated by treatment with polymyxin B, an inhibitor of LPS. Furthermore, the immunization of mice with gamma-PGA NPs carrying ovalbumin (OVA) as an antigen significantly induced antigen-specific CD8(+) T cells and antigen-specific production of interleukin-2, tumor necrosis factor alpha, and gamma interferon from the cells. Such activities of gamma-PGA NPs were more potent than those obtained with immunization with OVA plus aluminum hydroxide or OVA plus complete Freund's adjuvant. These results suggest that gamma-PGA NPs induce a CD8(+) T-cell response by activating innate immunity in a fashion different from that of LPS. Thus, gamma-PGA NPs may be an attractive candidate to be developed further as a vaccine adjuvant.
 ...
PMID:Modulation of gene expression related to Toll-like receptor signaling in dendritic cells by poly(gamma-glutamic acid) nanoparticles. 2021 77

Folate is necessary for the production and maintenance of new cells and important during periods of rapid cell division and growth. Tumor necrosis factor-alpha (TNF-alpha) is known as a stimulant of apoptotic cell death. The present study was aimed to evaluate the efficacy of folic acid (CAS 59-30-3) in prevention of apoptosis by inhibiting TNF-alpha action in ischemia-reperfusion (I/R) induced liver injury. Eighteen Wistar rats were subjected to 1 h of hepatic ischemia followed by 3 h reperfusion and were divided into sham-operated control Group (I) (n = 6), ischemia and reperfusion group administered 0.9% saline (5 ml/kg, p.o.) for 7 days (II) (n = 6), folic acid treated group (1 mg/kg body weight/treated daily by oral route for 7 days before induced ischemia-reperfusion maneuver) (III) (n = 6). Hepatic damage in rats was assessed in terms of serum alanine transaminases and aspartate transaminases. TNF-alpha concentration was measured in serum by enzyme linked immuno assay. Necrosis and apoptosis were measured by flow cytometry and fluorescence microscopy. Apoptotic marker Bcl-2 gene expression was measured by reverse transcriptase polymerase chain reaction (RTPCR) and Western Blot Analysis. Pathological changes were measured by transmission electron microscopy (TEM). Serum alanine transaminase (ALT), aspartate transaminase (AST) and TNF-alpha concentration increased significantly (p < 0.05) in rats with I/R induced injury as compared to sham operated control rats. Pretreatment with folic acid effectively counteracted the alternation in hepatic enzymes. TEM, expression of Bcl-2 protein and flow cytometry studies confirmed the restoration of cellular normalcy and accredits the cytoprotective role of folic acid against I/R induced hepatic injury. The present study demonstrated that elevated TNF-alpha activity directly related to apoptosis and folic acid inhibits apoptosis by inhibiting the action of TNF-alpha.
 ...
PMID:Inhibition by folic acid of tumor necrosis factor alpha and apoptosis following normothermic ischemia-reperfusion. 2112 13

Folic acid has been shown to decrease the incidence of neural tube defects (NTDs) in normal and hyperglycemic conditions, but the influence of folic acid on the development of central nervous system is not fully understood. Here, we aimed to explore the effects of folic acid, especially high dose of folic acid, on the characteristics of neural progenitors in embryos of hyperglycemic and diabetic mouse. Hyperglycemic and diabetic pregnant mice were given 3 mg/kg or 15 mg/kg folic acid from embryonic day 0.5 (E0.5) and were euthanased on E11.5, E13.5 or E18.5. The incidence of NTDs at E13.5 was counted. The proliferation, apoptosis and differentiation of neural progenitors and neuronal migration were determined using BrdU incorporation assay, TUNEL assay, immunofluorescence, Western blot and real-time reverse transcriptase polymerase chain reaction. Both normal and high doses of folic acid decreased the incidence of NTDs, promoted proliferation and reduced apoptosis of neuroepithelial cells in embryos of hyperglycemic and diabetic mice. Importantly, folic acid, especially at high dose, might affect the premature differentiation of neural progenitors in embryos of hyperglycemic and diabetic pregnancy. This may be attributed to changes of messenger RNA expression levels of some basic-helix-loop-helix transcription factors. In addition, folic acid might be involved in regulating neuronal migration in embryos of hyperglycemic and diabetic pregnancy. These findings suggest that periconceptional supplementation of folic acid, especially at high dose, may be a double-edged sword because it may result in undesirable outcomes affecting both the neuronal and glial differentiation in hyperglycemic and diabetic pregnancy.
 ...
PMID:Folic acid supplementation changes the fate of neural progenitors in mouse embryos of hyperglycemic and diabetic pregnancy. 2326 36


1 2 Next >>