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)

Diabetic mellitus confers a major risk of congenital malformations, and is associated with diabetic embryopathy, affecting multiple organs including the kidney. The DNA paired box-2 (Pax-2) gene is essential in nephrogenesis. We investigated whether high glucose alters Pax-2 gene expression and aimed to delineate its underlying mechanism(s) of action using both in vitro (mouse embryonic mesenchymal epithelial cells (MK4) and ex vivo (kidney explant from Hoxb7-green florescent protein (GFP) mice) approaches. Pax-2 gene expression was determined by reverse transcriptase-polymerase chain reaction, Western blotting, and immunofluorescent staining. A fusion gene containing the full-length 5'-flanking region of the human Pax-2 promoter linked to a luciferase reporter gene, pGL-2/hPax-2, was transfected into MK4 cells with or without dominant negative IkappaBalpha (DN IkappaBalpha) cotransfection. Fusion gene expression level was quantified by cellular luciferase activity. Reactive oxygen species (ROS) generation was measured by lucigenin assay. Embryonic kidneys from Hoxb7-GFP mice were cultured ex vivo. High D(+) glucose (25 mM), compared to normal glucose (5 mM), specifically induced Pax-2 gene expression in MK4 cells and kidney explants. High glucose-induced Pax-2 gene expression is mediated, at least in part, via ROS generation and activation of the nuclear factor kappa B signaling pathway, but not via protein kinase C, p38 mitogen-activated protein kinase (MAPK), and p44/42 MAPK signaling.
 ...
PMID:Reactive oxygen species and nuclear factor-kappa B pathway mediate high glucose-induced Pax-2 gene expression in mouse embryonic mesenchymal epithelial cells and kidney explants. 1698 13

The aim of this study was to test the selectivity, in-vivo effectiveness, and potential mechanism of action of a linomide analogue (N-phenyl-1,2-dihydro-4-hydroxyl-2-oxo-quinoline-3-carboxamide, Lin05) for inhibition of choroidal neovascularization. The selectivity of Lin05 was tested in cell proliferation assays with human umbilical vein endothelial cells (HUVEC) and a retinal pigmented epithelial cell line(ARPE-19). In-vivo anti-angiogenic effect of Lin05 was investigated utilizing an experimental laser-induced choroidal neovascularization (ECNV) model in adult Brown Norway rats. Western blot and/or reverse transcriptase-PCR was used to test the effect of Lin05 on potential targets. Our results indicate that Lin05 is at least an 8-fold more selective inhibitor of endothelial cell proliferation compared to RPE cells. Systemic administration of Lin05 in an ECNV model was associated with a significant decrease in both vascular leakage on fluorescein angiography and lesion size by histopathology (p = 0.02). No systemic toxicity was detected for Lin05 in major organs such as the liver, lung and kidneys. Lin05 did not inhibit VEGF-induced VEGFR2 (KDR) phosphorylation in HUVEC nor was associated with decreased VEGF gene expression. Also it did not inhibit insulin-like growth factor (IGF-1) and Epidermal Growth Factor (EGF) induced activation of p42/p44 MAPK activation. It inhibited both PDGF- and bFGF-induced p42/p44 MAPK phosphorylation. However, the effect on PDGF was variable in different HUVEC cells. In conclusion, Lin05 is a potential anti-angiogenic agent for the treatment of eye diseases associated with pathological neovascularization. The anti-angiogenic effect of Lin05 is likely through inhibition of bFGF but not through inhibition of the VEGF/KDR pathway.
 ...
PMID:Investigation of the potential utility of a linomide analogue for treatment of choroidal neovascularization. 2105

Diabetic peripheral neuropathy (DPN) is one of the most common complications of diabetes mellitus. One contributing factor to DPN is altered neurotrophism due to changes in the synthesis and expression of neurotrophins. Schwann cells (SCs) are the myelin-forming cells of the peripheral nervous system that promote nerve regeneration through the expression and secretion of neurotrophic factors (NTFs). Therefore, in this study, using SCs cultured in the presence of high levels of glucose for 24 h, with and without the p42/p44 mitogen-activated protein kinase (MAPK) inhibitor, PD98059, we investigated the effect of high glucose levels on SCs over a short period of time. The cultured cells were evaluated using 3(4,5-dimethylthiazol-2-yl)2,5-diphenyltetrazolium bromide (MTT) assay, Hoechst staining, immunocytochemistry, reverse transcriptase-polymerase chain reaction and western blot analysis. High glucose levels did not promote morphological abnormalities or decrease the viability of SCs. However, high glucose levels enhanced the expression of nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) and induced the activation of p42/p44 MAPK in cultured SCs in a dose-dependent manner. Additionally, the phosphorylation of p42/p44 MAPK may be associated with the expression of NTFs by SCs exposed to high glucose conditions; the excessive activation of p42/p44 MAPK inhibited the expression of NTFs. These observations demonstrate that exposure to high glucose levels lead to acutely elevated levels of NGF and BDNF in SCs over a short period of time, which may be involved in the p42/p44 MAPK pathway.
 ...
PMID:High glucose levels increase the expression of neurotrophic factors associated with p-p42/p44 MAPK in Schwann cells in vitro. 2255 24


<< Previous 1 2