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)

Interleukin-18 (IL-18) is a member of the IL-1 cytokine family and has proinflammatory activity. It has been detected in osteoarthritic (OA) and at higher levels in rheumatoid arthritic (RA) synovial tissue. Therefore we investigated major signal transduction pathways for their contribution to IL-18 expression. Here we report that cyclic adenosine monophosphate reduced and ionomycin increased IL-18 mRNA in RA synovial fibroblasts (SF) but not in OA SF. Moreover, activation of G-proteins by Mas-7 augmented IL-18 reverse transcriptase polymerase chain reaction signals in OA SF but not in RA SF. Specific protein kinase C activator phorbol myristate acetate reduced transcription and secretion of IL-18 in RA SF and OA SF. Staurosporine changed spontaneous IL-18 mRNA levels and increased the secretion of IL-18 protein. We conclude that G-protein activation and protein kinase C activation might partially be responsible for elevated IL-18 levels during RA.
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PMID:Interleukin-18 is regulated by G protein pathways and protein kinase signals in human fibroblasts. 1287 65

Abnormal gastro-oesophageal reflux and bile acids have been linked to the presence of Barrett's oesophageal premalignant lesion associated with an increase in mucin-producing goblet cells and MUC4 mucin gene overexpression. However, the molecular mechanisms underlying the regulation of MUC4 by bile acids are unknown. Since total bile is a complex mixture, we undertook to identify which bile acids are responsible for MUC4 up-regulation by using a wide panel of bile acids and their conjugates. MUC4 apomucin expression was studied by immunohistochemistry both in patient biopsies and OE33 oesophageal cancer cell line. MUC4 mRNA levels and promoter regulation were studied by reverse transcriptase-PCR and transient transfection assays respectively. We show that among the bile acids tested, taurocholic, taurodeoxycholic, taurochenodeoxycholic and glycocholic acids and sodium glycocholate are strong activators of MUC4 expression and that this regulation occurs at the transcriptional level. By using specific pharmacological inhibitors of mitogen-activated protein kinase, phosphatidylinositol 3-kinase, protein kinase A and protein kinase C, we demonstrate that bile acid-mediated up-regulation of MUC4 is promoter-specific and mainly involves activation of phosphatidylinositol 3-kinase. This new mechanism of regulation of MUC4 mucin gene points out an important role for bile acids as key molecules in targeting MUC4 overexpression in early stages of oesophageal carcinogenesis.
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PMID:Transcriptional regulation of human mucin MUC4 by bile acids in oesophageal cancer cells is promoter-dependent and involves activation of the phosphatidylinositol 3-kinase signalling pathway. 1458 90

Vascular endothelial growth factor (VEGF) is highly expressed in the airway of patients with asthma. Whether VEGF affects eosinophil function in vitro and if VEGF receptors are involved was tested. Eosinophils were from venous blood of healthy donors. Cell migration was studied by micropore filter assays. Signaling mechanisms required for VEGF-dependent migration were tested using signaling enzyme blockers. Expression of flt-1 and KDR/flk-1 mRNA in eosinophils was demonstrated in reverse transcriptase-polymerase chain reaction, and receptor expression was investigated by fluorescence-activated cell sorting analysis. Eosinophil cationic protein release was measured in eosinophil supernatants by enzyme-linked immunosorbent assay. VEGF significantly stimulated eosinophil chemotaxis via activation of protein kinase C and phosphatidylinositol 3'-kinase. The effect on migration was reversed by an antibody against VEGF receptor flt-1, but not by an antibody against KDR/flk-1. Expression of VEGF receptor flt-1 mRNA was shown and synthesis of VEGF receptor in eosinophils is suggested by detection of VEGF receptor immunoreactivity on the cell surface. Data suggest that VEGF receptor flt-1 is expressed by eosinophils whose activation with VEGF stimulates directed migration and release of eosinophil cationic protein. Thus, VEGF may play an important role in the modulation of eosinophilic inflammation.
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PMID:Expression and function of the vascular endothelial growth factor receptor FLT-1 in human eosinophils. 1460 15

To elucidate the underlying mechanisms involved in AIDS therapy-induced peripheral neuropathy, we have developed a model of nucleoside analog reverse transcriptase inhibitor-induced painful peripheral neuropathy in the rat, using 2',3'-dideoxycytidine (ddC), 2',3'-dideoxyinosine (ddI) and 2',3'-didehydro-3'-deoxythymidine (d4T), AIDS chemotherapeutic drugs that are also components of AIDS highly active anti-retroviral therapy. Administration of ddC, ddI and d4T produced dose-dependent mechanical hypersensitivity and allodynia. Peripheral administration of inhibitors of protein kinase A, protein kinase C, protein kinase G, p42/p44-mitogen-activated protein kinase (ERK1/2) and nitric oxide synthase, which have demonstrated anti-hyperalgesic effects in other models of metabolic and toxic painful peripheral neuropathies, had no effect on ddC-, ddI- and d4T-induced hypersensitivity. Since suramin, an anti-parasitic and anti-cancer drug, which shares with the anti-retroviral nucleoside analogs, mitochondrial toxicity, altered regulation of intracellular calcium, and a sensory neuropathy in humans, also produced mechanical hypersensitivity that was not sensitive to the above second messenger inhibitors we evaluated the role of intracellular calcium. Intradermal or spinal injection of intracellular calcium modulators (TMB-8 and Quin-2), which had no effect on nociception in control rats, significantly attenuated and together eliminated ddC and suramin-induced mechanical hypersensitivity. In electrophysiology experiments in ddC-treated rats, C-fibers demonstrated alterations in pattern of firing as indicated by changes in the distribution of interspike intervals to sustained suprathreshold stimuli without change in mechanical activation thresholds or in number of action potentials in response to threshold and suprathreshold stimulation. This study provides evidence for a novel, calcium-dependent, mechanism for neuropathic pain in a model of AIDS therapy-induced painful peripheral neuropathy.
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PMID:Novel mechanism of enhanced nociception in a model of AIDS therapy-induced painful peripheral neuropathy in the rat. 1471 1

Antimicrobial peptides of the beta-defensin family are expressed in all human epithelial tissues tested to date and have recently been the subject of vigorous investigation. Their localization and characteristics support the hypothesis that these peptides play a role in mucosal and skin defense. The lipophilic yeast Malassezia furfur is a saprophyte found in normal human cutaneous flora. Malassezia furfur is not only a saprophyte, but is also associated with several diseases such as Malassezia folliculitis, seborrheic dermatitis and some forms of atopic dermatitis, psoriasis and confluent and reticulate papillomatosis. Little is known about the mechanism by which M. furfur overcomes the natural barrier of the skin. To further define the role of the beta-defensins in the innate human skin immune response, we analyzed the mRNA expression of two human beta-defensins HBD-1 and HBD-2 in human keratinocytes treated with M. furfur. In addition, we looked into how M. furfur of TGF-beta1 and IL-10, cytokines that interfere with the development of protective cell immunity, regulate their expression. Finally, we examined the signal transduction mechanisms involved during M. furfur uptake. Cultured human keratinocytes were treated with M. furfur. The mRNA and protein expression were analyzed, respectively, by reverse transcriptase polymerase chain reaction (RT-PCR) and Western blotting. Our data demonstrate that M. furfur does not modify HBD-1 expression, whereas it up-regulates, via protein kinase C (PKC), the expression of HBD-2, TGFbeta-1 and IL-10 48 h after treatment. Our results suggest that beta-defensins are integral components of innate host defenses. They play an essential part in the resistance of the human skin surfaces against M. furfur uptake and other microbial invasion.
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PMID:Malassezia furfur induces the expression of beta-defensin-2 in human keratinocytes in a protein kinase C-dependent manner. 1496 22

The purpose of this study was to determine the effects of a novel aldose reductase inhibitor on lens protein kinase Cgamma (PKCgamma) levels in galactosemic dogs. Six-month old Beagles (12 total; 6 male and 6 female) were made galactosemic by feeding a diet of 40% galactose for 6 weeks. Three dogs per group were fed either control, normal diet, 40% galactose diet, 40% galactose diet with aldose reductase inhibitor at 100 mg/kg body weight per day given orally, or a control diet with aldose reductase inhibitor alone (1-H,7-H-5alpha,6,8,9-tetrahydro-1-oxopyran[4,3-beta](1) benzopyran, referred to herein as HAR-1). Lenses were removed and analyzed for toxicity by pathological examination. Lens polyol concentrations were determined by GC/MS. PKCgamma levels were determined by Western blot and by reverse transcriptase-polymerase chain reaction (RT-PCR). No toxicity was observed from the aldose reductase inhibitor when given at 100 mg/kg body weight per day for 6 weeks. Galactosemic dogs showed deterioration of lens cells. Deterioration included vacuole formation in the lens, cell lysis, and loss of cell nuclei. Galactosemic dogs given the HAR-1 appeared identical to control dogs. Polyol concentrations in the lenses were reduced by 50% in dogs fed the 40% galactose diet with the aldose reductase inhibitor, HAR-1. PKCgamma protein levels were reduced in the galactosemic dog lenses, but synthesis of PKCgamma was not affected, as measured by RT-PCR. The PKCgamma protein levels were similar to controls in dogs given the aldose reductase inhibitor, HAR-1, even when polyol concentrations remained 50% elevated above control levels. HAR-1, when given to control dogs, caused a reduction in the synthesis of PKCgamma mRNA but not in total PKCgamma protein levels. This study demonstrates the use of a novel aldose reductase inhibitor to control changes in PKCgamma in dog lens, a PKC that is known to control gap junction activity.
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PMID:Normalization of lens protein kinase Cgamma in galactosemic dogs by a novel aldose reductase inhibitor. 1509 23

Genes induced or suppressed by oxidized low-density lipoproteins (oxLDL) in human monocytic THP-1 cells were searched using the differential display reverse transcriptase polymerase chain reaction. One of the differentially expressed (up-regulated) cDNA fragments was found to contain sequences corresponding to monocyte chemotactic protein-3 (MCP-3). The stimulatory effect of the oxLDL on the expression of MCP-3 mRNA was both time- and dose-dependent. Treatment with GF109203X and genistein, inhibitors of protein kinase C and tyrosine kinase, respectively, had no effect on the induction of MCP-3 mRNA by oxLDL, while treatment with cycloheximide inhibited the induction. The induction was reproduced by the lipid components in oxLDL such as 9-HODE and 13-HODE, which are known to activate the peroxisome proliferator-activated receptor gamma (PPARgamma). Introduction of an endogenous PPARgamma ligand, 15d-PGJ2, in the culture of THP-1 cells resulted in the induction of MCP-3 gene expression. Furthermore, analyses of human atherosclerotic plaques revealed that the expressional pattern of MCP-3 in the regions of neointimal and necrotic core overlapped with that of PPARgamma. These results suggest that oxLDL delivers its signal for MCP-3 expression via PPARgamma, which may be further related to the atherogenesis.
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PMID:Oxidized low-density lipoproteins may induce expression of monocyte chemotactic protein-3 in atherosclerotic plaques. 1538 Oct 85

We reported previously that insulin inhibits the stimulatory effect of high glucose on the expression of angiotensinogen (ANG) gene in both rat immortalized renal proximal tubular cells (IRPTCs) and non-diabetic rat renal proximal tubular cells (RPTCs), but has no effect in diabetic rat RPTCs. In the present study we investigated whether hyperglycaemia-induced resistance to the insulin-induced inhibition of expression of the ANG gene is mediated via the generation of reactive oxygen species (ROS) in RPTCs. Rat IRPTCs were cultured for 2 weeks in high-glucose (25 mM) or normal-glucose (5 mM) medium plus angiotensin II (Ang II) with or without a superoxide scavenger (tiron), or inhibitors of: NADPH oxidase (diphenylene iodinium, DPI), Ang II type 1 and 2 receptors (losartan and PD123319), angiotensin-converting enzyme (perindopril), protein kinase C (GF 109203X), or glutamine:fructose-6-phosphate amino-transferase (azaserine). Cellular generation of ROS, and ANG and renin mRNA levels were assessed by lucigenin assay and specific reverse transcriptase-PCR respectively. Phosphorylation of p44/42 mitogen-activated protein kinase (p44/42 MAPK) was evaluated by western blotting. Prolonged exposure of IRPTCs to high concentrations of glucose or Ang II evoked generation of ROS and resistance to the insulin-induced inhibition of expression of the ANG gene and of p44/42 MAPK phosphorylation. Co-incubation of IRPTCs with tiron, DPI, losartan, PD123319, perindopril, GF 109203X or azaserine prevented ROS generation, restoring the inhibitory action of insulin on ANG gene expression and on p44/42 MAPK phosphorylation. In conclusion, our studies demonstrate that blockade of both ROS generation and activation of the intrarenal renin-angiotensin system improves the inhibitory action of insulin on ANG gene expression in IRPTCs in conditions of high glucose.
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PMID:Reactive oxygen species blockade and action of insulin on expression of angiotensinogen gene in proximal tubular cells. 1559 Sep 80

Hypericin is a naturally occurring substance found in the common St. John's Wort (Hypericum species) and can also be synthesized from the anthraquinone derivative emodin. As the main component of Hypericum perforatum, it has traditionally been used throughout the history of folk medicine. In the last three decades, hypericin has also become the subject of intensive biochemical research and is proving to be a multifunctional agent in drug and medicinal applications. Recent studies report antidepressive, antineoplastic, antitumor and antiviral (human immunodeficiency and hepatitis C virus) activities of hypericin; intriguing information even if confirmation of data is incomplete and mechanisms of these activities still remain largely unexplained. In other contemporary studies, screening hypericin for inhibitory effects on various pharmaceutically important enzymes such as MAO (monoaminoxidase), PKC (protein kinase C), dopamine-beta-hydroxylase, reverse transcriptase, telomerase and CYP (cytochrome P450), has yielded results supporting therapeutic potential. Research of hypericin and its effect on GABA-activated (gamma amino butyric acid) currents and NMDA (N-methyl-D-aspartat) receptors also indicate the therapeutic potential of this substance whereby new insights in stroke research (apoplexy) are expected. Also in the relatively newly established fields of medical photochemistry and photobiology, intensive research reveals hypericin to be a promising novel therapeutic and diagnostic agent in treatment and detection of cancer (photodynamic activation of free radical production). Hypericin is not new to the research community, but it is achieving a new and promising status as an effective agent in medical diagnostic and therapeutic applications. New, although controversial data, over the recent years dictate further research, re-evaluation and discussion of this substance. Our up-to-date summary of hypericin, its activities and potentials, is aimed to contribute to this process.
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PMID:Hypericin--the facts about a controversial agent. 1563 60

A 1.3 kb satellite DNA from a size defined genomic library of mammal Bubalus bubalis was cloned and sequenced. The clone pSB1 is AT rich with 447 A (33.6%), 262 C (19.7%), 240 G (19.0%) and 383 T (28.8%). There were about 1400 copies of contig in the bubaline genome but it did not uncover allele length variation when used as probe in conjunction with a number of restriction enzymes. The contig pSB1 is not conserved evolutionarily and cross hybridizes only with the Bovideae family. A set of primers from 5' (nt 422 to 441) and 3' (nt 962 to 947) deduced from the clone used for PCR amplification with four members of the Bovideae family gave the expected 530 bp band of equal intensity indicating a similar number of copies in all the four species namely Bos indicus, Capra hircus, Ovis aries and Bubalus bubalis. Expression studies with pSB1 following slot-blot hybridization with total RNA isolated from ovary, testes, kidney, lung and spleen revealed varying signal intensities in all the tissues with a most prominent signal in spleen but a faint one in ovary. Further sequence analysis revealed the presence of several eukaryotic transcriptional elements such as NF-E1, Poly-A signal, lariat consensus sequences, and CTF/NF1 binding sites. Blast search showed 90% sequence similarity with the reverse transcriptase gene of Bos taurus and sequences from nt 283 to 636 within the contig showed highly conserved reverse transcriptase like signatures along with N-glycosylation and protein kinase C phosphorylation sites. From the data we conclude that the pSB1 representing satellite DNA is associated with transcribing sequences. The prospect of identifying functional genes linked with the satellite fraction in higher vertebrates is discussed.
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PMID:A 1.3 kb satellite DNA from Bubalus bubalis not conserved evolutionarily is transcribed. 1566 49


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