1,720,981 research outputs found
Nuclear opioid receptors activate opioid peptide gene transcription in isolated myocardial nuclei
No full textOpioid-binding sites were identified in highly purified nuclei isolated from hamster ventricular myocardial cells. A significant increase in the maximal binding capacity for a kappa opioid receptor ligand was observed in myocardial nuclei from BIO 14.6 cardiomyopathic hamsters, as compared with nuclei obtained from normal myocytes of the F1B strain. The exposure of isolated nuclei to dynorphin B, a natural agonist of kappa opioid receptors, markedly increased opioid peptide gene transcription. The transcriptional effect was mediated by nuclear protein kinase C activation and occurred at a higher rate in nuclei from cardiomyopathic myocytes than in nuclei isolated from normal cells. Thus, a nuclear endorphinergic system may play an intracrine role in the regulation of gene transcription under both normal and pathological conditions
The anti-metastatic agent imidazolium trans-imidazoledimethylsulfoxide-tetrachlororuthenate induces endothelial cell apoptosis by inhibiting the mitogen-activated protein kinase/extracellular signal-regulated kinase signaling pathway
No full textImidazolium trans-imidazoledimethylsulfoxide-tetrachlororuthenate (NAMI-A) is a new ruthenium compound active against lung metastasis in vivo and tumor cell invasion in vitro. Since angiogenesis was recognized as a key event in the metastasizing process, the manipulation of neo-vessel formation has been developed as a new therapeutic approach. Within this context, a pivotal role for apoptosis in regulating cellular growth has been proposed. In the present study, we exposed to NAMI-A the spontaneously transformed human endothelial cell line ECV304 and assessed a number of apoptosis-related features, including the DNA degradation rate, the activation of caspase-3 protease, the expression of Hsp27, and the release of cytochrome c. Cell treatment with NAMI-A elicited a significant increment in the apoptotic response, as indicated by DNA fragmentation and caspase-3 activation, two classical hallmarks of cellular suicide. Furthermore, NAMI-A was able to down-regulate Hsp27 protein expression and provoke the release of mitochondrial cytochrome c in the cytosol. Here, we analyze the involvement of the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) signal transduction pathway in the induction of apoptosis elicited by NAMI-A. Such a response was associated with a marked inhibition of MAPK/ERK kinase (MEK) and ERK phosphorylation with a time course and dose dependency overlapping those observed throughout NAMI-A-induced apoptosis. In addition, we report that PD98059, a selective MEK inhibitor, is able to induce apoptosis by itself in the ECV304 cell line. These results suggest that inhibition of MEK/ERK signaling by NAMI-A may have an important role in modulating an apoptotic event in ECV304. (C) 2002 Elsevier Science (USA). All rights reserved
Heparin inhibits phorbol ester-induced ornithine decarboxylase gene expression in endothelial cells
No full textGlycosaminoglycans regulate angiogenesis by affecting the availability of different growth factors for the endothelial cell (EC), However, little is known about the molecular and functional consequences resulting from direct interaction of these polyclectrolytes with the EC, Here me show that heparin markedly inhibited serum-stimulated DNA synthesis and ornithine decarboxylase (ODC) mRNA expression in human endothelial cells (HEC), About 50% of the serum effect on DNA synthesis and ODC gene expression was prevented by the selective protein kinase C (PI(C) inhibitor chelerythrine or by PKC down-regulation, Heparin was ineffective in counteracting that part of the effect of serum that,vas resistant to PKC inhibition or down-regulation. In serum-free cultured HEC, heparin completely abolished the increase in DNA synthesis and ODC mRNA expression elicited by a number of PKC activators, Cell exposure to difluoromethylornithine, an irreversible inhibitor of ODC enzyme, dramatically antagonised both serum- and phorbol 12-myristate 13-acetate (PMA)-stimulated DNA synthesis, These results suggest that inhibition of PKC-mediated ODC gene expression by glycosaminoglycans mag represent an important mechanism in the regulation of HEC proliferation. (C) 1998 Federation of European Biochemical Societies
Phenotypic characterisation and molecular changes induced by gestational diabetes mellitus (GDM) on human umbilical endothelial cells: focus on the KDM2B/miR-101/EZH2 pathway
No full textHeparin inhibits phorbol ester-induced ornithine decarboxylase gene expression in endothelial cells
No full textPKC/Raf/MEK/ERK signaling pathway modulates native-LDL-induced E2F-1 gene expression and endothelial cell proliferation
No full textBackground and objectives: The interactions of low-density lipoprotein (LDL) with the endothelium are thought to play a major role in the development of atherosclerosis. Due to this reason, the molecular sequelae of events resulting from native LDL (N-LDL) interaction with human endothelial cells (HECs) are largely under investigation. Methods and results: Here, we report that the exposure of serum-free HECs to different concentrations of N-LDL-cholesterol (LDL-chol) elicited a time- and dose-dependent induction of DNA synthesis. The exposure of serum-free HECs to N-LDL was able to elicit a time- and dose-dependent increase of protein kinase C (PKC) activity that, along with the activation of the Raf/mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) signaling pathway, leads to an increase in E2F-1 gene expression, In addition, the treatment of HECs with N-LDL was also able to induce both E2F-1 gene transcription and protein expression. These N-LDL-aroused responses were dramatically counteracted by PKC inhibition or down regulation. Similarly to what observed for Raf/MEK/ERK activation and E2F-1 gene expression, the inhibition of PKC as well as its down regulation, significantly lowered the DNA synthesis induced by N-LDL in serum-free HECs. Conclusions: These results suggest that the activation of PKC/Raf/MEK/ERK-mediated events controlling E2F-1 gene expression by N-LDL may represent an important mechanism in the regulation of HECs proliferation during normal and pathological processes. (C) 2003 European Society of Cardiology. Published by Elsevier B.V. All rights reserved
Resveratrol-elicited PKC inhibition counteracts NOX-mediated endothelial to mesenchymal transition in human retinal endothelial cells exposed to high glucose
Full text linkExposure of human pulmonary vascular smooth muscle cells to sera from patients with systemic sclerosis increases intracellular reactive oxygen species levels
No full textNAMI-A inhibits the PMA-induced ODC gene expression in ECV304 cells: Involvement of PKC/Raf/Mek/ERK signalling pathway
No full textImidazolium trans-imidazole dimethyl sulfoxide tetrachlororuthenate (NAMI-A) is a new compound active against lung metastasis of solid metastasizing tumours. While its in vivo effect has been studied, the molecular insights that underlie its action are largely unknown. Among the possible pathways responsible for malignant transformation, PKC arose as one of the most promising targets for new antineoplastic drugs. We demonstrated the capability of NAMI-A of inhibiting PMA induced-PKC activity in ECV304 in a dose-dependent fashion. Furthermore, NAMI-A through modulation of PKC activity has been proved capable of reducing the phorbol ester induced expression of ornithine decarboxilase (ODC) gene and to abrogate the activation of the Raf/MEK/ERK pathway. Taken together these results suggest that many of the in vivo outcomes of NAMI-A treatment may be the result of a direct action on PKC
Heparin down-regulates the phorbol ester-induced protein kinase C gene expression in human endothelial cells: enzyme-mediated autoregulation of protein kinase C-alpha and -delta genes
No full textOverexpression of protein kinase C-delta and protein kinase C-delta has been shown to modulate a number of biological effects, including the cell growth and differentiation. We hypothesized that heparin, a potent antimitogenic drug, could affect the cell proliferation by inhibiting the expression of specific protein kinase C genes. Heparin, markedly but not completely, inhibited the serum-stimulated protein kinase C-delta and -delta mRNA expression. Protein kinase C inhibition or downregulation significantly decreased the serum-induced protein kinase C isoenzyme gene expression. Heparin failed to inhibit the residual effect of serum that was resistant to the above-mentioned treatments. Phorbol 12-myristate 13-acetate elicited an increase of protein kinase C isoenzyme gene expression that was completely prevented by protein kinase C inhibition or downregulation. Heparin dose-dependently counteracted and ultimately abolished the increase in the protein kinase C isoenzyme gene expression elicited by phorbol 12-myristate 13-acetate, These results suggest that the inhibition of an autoregulatory role wielded by protein kinase C on the protein kinase C-delta and -delta gene expression might represent a possible mechanism by which glycosaminoglycans modulate the cell growth. (C) 1999 Federation of European Biochemical Societies
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