Search results for "protein kinase C"
showing 10 items of 180 documents
Effects of ouabain on human bronchial muscle in vitro
2003
The effects of ouabain, an inhibitor of the plasmalemmal Na(+)/K(+)-ATPase activity, were examined in human isolated bronchus. Ouabain produced concentration-dependent contraction with -logEC(50)=7.16+/-0.11 and maximal effect of 67+/-4% of the response to acetylcholine (1 mM). Ouabain (10 microM)-induced contraction was epithelium-independent and was not depressed by inhibitors of cyclooxygenase and lipoxygenase, antagonists of muscarinic, histamine H(1)-receptors and alpha-adrenoceptors, or neuronal Na(+) channel blockade. The inhibition of ouabain contraction in tissues bathed in K(+)-free medium, and the inhibition by ouabain of the K(+)-induced relaxation confirm that the contractile a…
Involvement of PKC and NF-κB in Nitric Oxide Induced Apoptosis in Human Coronary Artery Smooth Muscle Cells
2001
Apoptosis of vascular smooth muscle cells is critically involved in progression of atherosclerosis and may prevent intimal hyperplasia in restenosis and vascular remodeling. Nitric oxide (NO) is known to induce apoptosis, but the signaling pathways still remain unclear. We investigated p53 accumulation, protein kinase C (PKC) activation and nuclear transcription factor (NF-kappaB) binding activity as possible signaling mechanisms of NO-induced apoptosis. Apoptosis was induced dose-dependently with the NO-donors sodiumnitroprusside (SNP: 232+/-48%) and SIN-1 (241+/-90% of actinomycin D induced apoptosis; means +/- SEM, *por =0.05 vs. control) in HSMC. Inhibition of PKC significantly attenuat…
Modulation of mutagenicity by phosphorylation of mutagen-metabolizing enzymes.
2004
In this Minireview, we discuss our findings on phosphorylation of cytochromes P450 (CYP) and influence of this modification on metabolic toxification and/or detoxification of a variety of mutagens. We show that phosphorylation drastically interferes with the mutagenicity of several classes of compounds which are of high human relevance (cytostatic drugs of the cyclophosphamide type, aromatic amines/amides, and nitrosamines). We illustrate this by describing the consequences of the stimulation of protein kinase A (with the example of CYP2B1 and CYP2E1), stimulation of protein kinase C, and inhibition of protein phosphatases PP1 and PP2A (with the example of CYP1A1 and CYP1A2). We discuss a p…
Analysis of phosphorylation-dependent modulation of Kv1.1 potassium channels.
2003
The voltage-gated potassium channel Kv1.1 contains phosphorylation sites for protein kinase A (PKA) and protein kinase C (PKC). To study Kv1.1 protein expression and cellular distribution in regard to its level of phosphorylation, the effects of PKA and PKC activation on Kv1.1 were investigated in HEK 293 cells stably transfected with Kv1.1 (HEK 293/1). Without kinase activation, HEK 293/1 cells carry unphosphorylated Kv1.1 protein in the plasma membranes, whereas large amounts of phosphorylated and unphosphorylated Kv1.1 protein were located intracellularly. Activation of PKA resulted in phosphorylation of intracellular Kv1.1 protein, followed by a rapid translocation of Kv1.1 into the pla…
The transport activity of the human cationic amino acid transporter hCAT-1 is downregulated by activation of protein kinase C
2001
1 The human cationic amino acid transporter hCAT-1 contains several consensus sequences for phosphorylation by protein kinase C (PKC). This study investigates the eAect of PKC activation on hCAT-1-mediated transport. 2 When expressed in Xenopus laevis oocytes, hCAT-1-mediated L-arginine transport was reduced to 44+3% after a 30 min treatment of the oocytes with 100 nM phorbol-12-myristate-13-acetate (PMA). 4a-phorbol-12,13-didecanoate (4a-PDD, 100 nM) had no eAect. 3 In EA.hy926 endothelial cells, maximal inhibition of hCAT-1-mediated L-arginine transport (to 3‐11% of control) was observed after treatment of the cells with 100 nM PMA for 4 h. A 20‐30 h exposure of the cells to 100 nM PMA le…
Effects of the prostanoid EP3 -receptor agonists M&B 28767 and GR 63799X on infarct size caused by regional myocardial ischaemia in the anaesthet…
1999
1. This study investigates the effects of two agonists of the prostanoid EP3-receptor (MB PEEP: 1-2 mmHg) and subjected to occlusion of the left anterior descending coronary artery (LAD, for 7.5, 15, 25, 35, 45 or 60 min) followed by reperfusion (2 h). Infarct size was determined by staining of viable myocardium with a tetrazolium stain (NBT), histological evaluation by light and electron microscopy and determination of the plasma levels of cardiac troponin T. 3. MB saline-control, n=8) to 39+/-6 and 38+/-4% of the area at risk, without causing a significant fall in blood pressure. Pretreatment of rats with 5-hydroxydecanoate (5-HD), an inhibitor of ATP-sensitive potassium channels, attenua…
The cAMP Pathway Sensitizes VR1 Expressed in Oocytes from <i>Xenopus laevis</i> and in CHO Cells
2003
The vanilloid receptor 1 (VR1) is a heat-activated cation channel which also responds to capsaicin and other chemical stimuli. Protein kinase C has a stimulatory effect on VR1 activity, either alone or after activation with capsaicin. The influence of the cAMP-signaling pathway on the effects of capsaicin is controversial. To clarify this, the actions of capsaicin and the modulatory effects of forskolin, pCPT-cAMP, and isobutylmethylxanthine were studied in <i>Xenopus laevis</i> oocytes expressing rat VR1 and in CHO cells expressing human VR1. Capsaicin activated the VR1 channel and increased the intracellular calcium concentration. The effects of capsaicin were enhanced by fors…
Prevention of the acute neurotoxic effects of phenytoin on rat peripheral nerve by H7, an inhibitor of protein kinase C.
1992
Abstract The neurotoxic effects of a single dose of phenytoin (150 mg/kg body weight) alone or 30 min after H7 (a protein kinase C inhibitor) injection (20 mg/kg body weight) were investigated in terms of peripheral neuromuscular function and Na + ,K + -ATPase activity of the sciatic nerve. This intraperitoneal injection of phenytoin induced complete blockade of muscle action potentials in the dorsal segmental muscles of the rat tail evoked by electric stimulation of the caudal nerve and a 40% decrease in the Na + ,K + -ATPase activity of the rat sciatic nerve when compared with control values, measured as the difference between total and ouabain-insensitive ATPase activity. Prior administr…
n-3 PUFAs modulate T-cell activation via protein kinase C-α and -ε and the NF-κB signaling pathway
2005
We elucidated the mechanisms of action of two n-3 PUFAs, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), in Jurkat T-cells. Both DHA and EPA were principally incorporated into phospholipids in the following order: phosphatidylcholine < phosphatidylethanolamine < phosphatidylinositol/phosphatidylserine. Furthermore, two isoforms of phospholipase A(2) (i.e., calcium-dependent and calcium-independent) were implicated in the release of DHA and EPA, respectively, during activation of these cells. The two fatty acids inhibited the phorbol 12-myristate 13-acetate (PMA)-induced plasma membrane translocation of protein kinase C (PKC)-alpha and -epsilon. The two n-3 PUFAs also inhibited t…
Modulation of neuronal phospholipase D activity under depolarizing conditions
1999
Neuronal phospholipase D (PLD) activity was hypothesized to be involved in vesicle trafficking and endocytosis and, possibly, transmitter release. We here report that prolonged depolarization of rat hippocampal slices by potassium chloride (KCl) or 4-aminopyridine inhibited PLD activity. Similarly, PLD activity in rat cortical synaptosomes was significantly inhibited by depolarizing agents including veratridine and ouabain. Inhibition of calcium/calmodulin kinase II (CaMKII) which positively modulates synaptosomal PLD activity [Sarri et al. (1998) FEBS Lett. 440, 287-290] by KN-62 caused a further reduction of PLD activity in depolarized synaptosomes. Depolarization-induced inhibition of PL…