Search results for "PK"
showing 10 items of 758 documents
Activation of MAP kinase signaling pathway in the mussel Mytilus galloprovincialis as biomarker of environmental pollution
2010
Stimulation of MAP kinase signal transduction pathway by various stressful stimuli was investigated in the marine bivalve Mytilus galloprovincialis. Analyses were performed in animals exposed in laboratory to selected pollutants and in mussels collected in winter and summer along the eastern Adriatic coast (Croatia). Effects of oxidative stress, induced by tributyltin, hydrogen peroxide and water soluble fraction of diesel fuel on the activation/phosphorylation of the three Mitogen-Activated Protein Kinases (MAPKs) p38, JNK and ERK using a newly developed ELISA procedure were evaluated. MAP kinase activation was analyzed 1 h after exposure of mussels to chemical agents, and after recovery p…
P38 MAP Kinase Signaling Is Required for the Conversion of CD4+CD25− T Cells into iTreg
2008
CD4+CD25+ regulatory T cells (Treg) are important mediators of immune tolerance. A subset of Treg can be generated in the periphery by TGF-beta dependent conversion of conventional CD4+CD25− T cells into induced Treg (iTreg). In chronic viral infection or malignancy, such induced iTreg, which limit the depletion of aberrant or infected cells, may be of pathogenic relevance. To identify potential targets for therapeutic intervention, we investigated the TGF-beta signaling in Treg. In contrast to conventional CD4+ T cells, Treg exhibited marked activation of the p38 MAP kinase pathway. Inhibition of p38 MAP kinase activity prevented the TGF-beta-dependent conversion of CD4+CD25− T cells into …
Activation of MAP kinase p38 is critical for the cell-cycle–controlled suppressor function of regulatory T cells
2007
AbstractRegulatory T cells play an essential role in the control of self-tolerance and processes of adaptive immunity. Tolerogenic IL-10–modulated human dendritic cells (IL-10DCs) induce anergic T cells with strong suppressive properties (iTregs) that inhibit the activation of effector T cells. In this study, we evaluated the interaction between cell-cycle regulation and intracellular signaling in these iTregs. Analysis of signal transduction events revealed a down-regulation of the mitogen-activated protein kinases (MAPKs) Jun N-terminal kinase (JNK) and a nonactivation of extracellular-signal–regulated kinase (ERK) in contrast to a marked activation of p38 MAPK and the p38 effector MAPK-a…
Effects of Scrophularia ningpoensis Hemsl. on Inhibition of Proliferation, Apoptosis Induction and NF-κB Signaling of Immortalized and Cancer Cell Li…
2012
Scrophularia ningpoensis has been used in China for centuries as a herbal tea to treat various diseases. Based on the numerous animal studies on its pharmaceutical effects and the long time clinical experiences, we studied the molecular and cellular mechanism underlying the bioactivity of aqueous extract of Scrophularia and its isolated compounds. Seven isolated compounds, unlike Scrophularia extract, failed to induce cytotoxicity on HaCaT cells, but their combination improved the effect of extract. Tumor cell line selectivity was not observed, when we studied its cytotoxic effect on melanoma cell lines. The apoptotic and anti-inflammatory effects of Scrophularia extract have been demonstra…
Evolution of osmosensing signal transduction in Metazoa: stress-activated protein kinases p38 and JNK.
2001
Sponges (Porifera) represent the most basal branch of the Metazoa alive today. We show that two central stress-activated protein kinases involved in the osmosensing pathway, p38 mitogen-activated protein kinase (MAPK) and JNK, can complement for the ancestral MAPK Hog1 in the yeast Saccharomyces cerevisiae. S. cerevisiae mutants lacking Hog1 (hog1-Delta 1) have been complemented with the sponge SDJNK and SDp38 genes. Western blotting has revealed that, after transformation, the hog1-Delta 1+ SDJNK(sense) and hog1-Delta 1+ SDp38(sense) clones express the sponge proteins. Functional studies have demonstrated that the complemented clones grow under hyperosmotic conditions (0.6 M NaCl). Further…
Synergistic Growth Inhibitory Activity of Combined Mek/Mtor Pathway Blockade in Pten-Null Cancers
2014
ABSTRACT Aim: We have recently shown that induction of PTEN expression plays an integral role in MEK inhibitors' antitumor activity. Here we hypothesize that PTEN status critically influences the functional outcome of combined MEK and PI3K/mTOR inhibition. Methods: Single and combined MEK (trametinib, T) and mTOR (everolimus, E) blockade were assessed in a panel of cancer cell lines and in patient-derived lung and colon cancer stem cells (L- or C-CSC). Pharmacologic interactions were analyzed by conservative isobologram analysis. PTEN role was assessed by shRNA-mediated silencing or overexpression by stable transfection. Treatment-induced changes in the phosphoproteome were analyzed by anti…
Apelin treatment increases complete Fatty Acid oxidation, mitochondrial oxidative capacity, and biogenesis in muscle of insulin-resistant mice.
2012
Both acute and chronic apelin treatment have been shown to improve insulin sensitivity in mice. However, the effects of apelin on fatty acid oxidation (FAO) during obesity-related insulin resistance have not yet been addressed. Thus, the aim of the current study was to determine the impact of chronic treatment on lipid use, especially in skeletal muscles. High-fat diet (HFD)-induced obese and insulin-resistant mice treated by an apelin injection (0.1 μmol/kg/day i.p.) during 4 weeks had decreased fat mass, glycemia, and plasma levels of triglycerides and were protected from hyperinsulinemia compared with HFD PBS-treated mice. Indirect calorimetry experiments showed that apelin-treated mice…
Dažādo metālisko elementu noteikšana ķērpjos (Parmelia sulcata) Kupravas apkārtnē
2022
Dažādu metālisko elementu noteikšana ķērpjos (Parmelia sulcata) Kupravas apkārtnē. Freimanis R., zinātniskā darba vadītājs Ķīm. mag. Lazarenko V. Bakalaura darbs, 31 lpp., 7 attēli, 9 tabulas, 28 literatūras avoti, 3 pielikumi. Latviešu valodā. Bakalaura darba izstrādes ietvaros, tika analizēts dažādo metālisko elementu saturs lapu ķērpju sugā (Parmelia sulcata) Kupravas apkārtnē. Tika izvēlētas trīs dažādas Kupravas apkārtnes teritorijas – bijušās Kupravas drenu cauruļu rūpnīcas teritorija, Kupravas dzīvojamais rajons, bijušajā militārās armijas daļa un Strautu mežs, kas atrodas ~6 km attālumā no Kupravas, kā tīrāka teritorija. Metālisko elementu saturs ķērpjos (Parmelia sulcata) tika note…
Colony-stimulating factor-1-induced oscillations in phosphatidylinositol-3 kinase/AKT are required for caspase activation in monocytes undergoing dif…
2009
Abstract The differentiation of human peripheral blood monocytes into resident macrophages is driven by colony-stimulating factor-1 (CSF-1), which upon interaction with CSF-1 receptor (CSF-1R) induces within minutes the phosphorylation of its cytoplasmic tyrosine residues and the activation of multiple signaling complexes. Caspase-8 and -3 are activated at day 2 to 3 and contribute to macrophage differentiation, for example, through cleavage of nucleophosmin. Here, we show that the phosphatidylinositol-3 kinase and the downstream serine/threonine kinase AKT connect CSF-1R activation to caspase-8 cleavage. Most importantly, we demonstrate that successive waves of AKT activation with increasi…
Systematic study of the physicochemical properties of a homologous series of aminobisphosphonates
2012
ABSTRACT: Aminobisphosphonates, e.g., alendronate and neridronate, are a well known class of molecules used as drugs for various bone diseases. Although these molecules have been available for decades, a detailed understanding of their most important physicochemical properties under comparable conditions is lacking. In this study, ten aminobisphosphonates, H2N(CH2)nC(OH)[P(O)(OH)2]2, in which n = 2-5, 7-11 and 15 have been synthesized. Their aqueous solubility as a function of temperature and pH, pKa-values, thermal stability, IR absorptions, and NMR spectral data for both liquid (1H, 13C, 31P-NMR) and solid state (13C, 15N and 31P-CPMAS NMR) were determined. Peer reviewed