Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.11.13 (protein kinase C)
 49,245 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Angiotensin II (AII, 0.1 nM) increased concentration dependently the sensitivity of rabbit aortic rings to low concentrations of noradrenaline. This was not associated with increases in noradrenaline-induced 45Ca2+ uptake or efflux and was prevented by the protein kinase C (PKC) inhibitors staurosporine (0.01 microM) and calphostin C (0.1 microM). Pretreatment of the rings with PMA (phorbol-12-myristate-13-acetate, 0.1 and 1 microM, 24 h at 4 degrees C) abolished the potentiation phenomenon. We conclude that AII potentiation of noradrenaline-induced vascular tone may be due to a PKC-mediated increase in intracellular sensitivity of the contractile apparatus to Ca2+.
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PMID:Further evidence from an elastic artery that angiotensin II amplifies noradrenaline-induced contraction through activation of protein kinase C. 128 May 95

The actin cytoskeleton of mesangial cells (MC) plays an important role in the contractile response to agonists as well as in the endocytosis of macromolecules. A quantitative study of the F-actin content of MC by the rhodamine-phalloidin binding assay was carried out. Angiotensin II (ANG II) (10(-6) M) significantly increased the F-actin content of MC by 30 min and at later time periods, with increases ranging from 31 to 46%. Arginine vasopressin (10(-8) M) produced a transient decrease of F-actin content of MC at 30 s but then significantly enhanced the F-actin content at later time periods. There was no change in total actin and protein content of MC at 30 min in the presence of either agent. Thus, the increase in F-actin is related to a shift in the G- to F-actin ratio and not to the synthesis of new F-actin. Because the incubation of MC with 1 (5-isoquinolinylsulfonyl)-2-methylpiperazine, an inhibitor of protein kinase C, did not attenuate the ANG II-induced increase in the F-actin content of MC, the shift does not appear to be mediated by the activation of protein kinase C. The removal of external calcium did not prevent the increase in F-actin. Dibutyryl cAMP (5 x 10(-4) M), a smooth muscle cell and MC relaxant, did not alter the F-actin content in MC, and 10(-5) M cytochalasin B significantly lowered F-actin content.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of angiotensin II and arginine vasopressin on F-actin content of cultured mesangial cells. 132 58

Angiotensin II (ANG II) was shown to modulate transport in the renal proximal tubule through both inhibition of adenylate cyclase and protein kinase C (PKC) activation. We evaluated the effects of ANG II on adenosine 3',5'-cyclic monophosphate (cAMP) content and Na-H exchange activity (amiloride-sensitive Na influx) in two strains of opossum kidney (OK) cells originating from different sources, OK-VD and OK-RR cells. In OK-VD cells, ANG II inhibited basal and parathyroid hormone (PTH)-induced cAMP generation in a pertussis toxin-sensitive manner and reversed PTH inhibition of Na-H exchange. These effects of ANG II were prevented by PD 123319, a selective nonpeptide antagonist of AT2 receptors. In contrast, DuP 753, which antagonizes selectively AT1 receptors, had no effect. In OK-RR cells, ANG II had no effect on cAMP content and decreased Na-H exchange activity. The effect of ANG II persisted in the presence of PTH but was abolished by PKC downregulation and by DuP 753, but not by PD 123319. In conclusion, two types of ANG II receptors, coupled to distinct signaling pathways, were expressed independently in OK cells originating from two different sources and mediated opposite effects of ANG II on Na-H exchange activity. Those models provide a powerful tool for studying the intracellular steps involved in the tubular effects of ANG II and to evaluate the effect of pharmacological inhibitors of ANG II binding to its receptors.
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PMID:Modulation of Na-H exchange activity by angiotensin II in opossum kidney cells. 133 86

Angiotensin II (AII) is a major regulator of cardiovascular function and fluid homeostasis. Recently, the cDNA for an AII receptor (AT1) was cloned from rat smooth muscle and bovine adrenal. To search for AII receptor subtypes, we amplified rat adrenal cortex cDNA by PCR using primers based on the AT1 receptor. The product was distinct from the AT1 receptor as indicated by restriction enzyme analysis and DNA sequencing. A full-length cDNA clone (2.2 kilobase pairs) encoding a novel AII receptor (AT3) was obtained by screening an adrenal cortex library. The AT3 cDNA encodes a Mr 40,959 protein with 95% amino acid identity to the rat smooth muscle receptor, but the overall nucleotide similarity is 71% due to low homology in the 5'- (58%) and 3'- (62%) untranslated regions. Expressed AT3 receptors in Xenopus oocytes and COS-7 cells mediate agonist-induced Ca2+ mobilization but are pharmacologically distinct from the AT1 receptors. AT3 mRNA is most abundant in the adrenal cortex and pituitary and differs from AT1 mRNA in its tissue distribution. The structural features of the AT3 receptor, including two additional potential phosphorylation sites for protein kinase C, could be related to the distinctive binding properties of the adrenal and vascular receptors and to their differential regulation during altered sodium intake.
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PMID:Cloning and expression of a novel angiotensin II receptor subtype. 137 2

We investigated whether the enhanced contractile response to norepinephrine caused by a subthreshold concentration of angiotensin II was associated with an increased 45Ca++ influx or net uptake. Rabbit facial artery segments were mounted isometrically to measure the 45Ca++ influx and net uptake in response to norepinephrine. The contractile response to norepinephrine (3 microM) in the presence of angiotensin II (0.1 nM) was 149.5 +/- 7.4% of control. This response amplification was not associated with changes in norepinephrine-induced 45Ca++ influx or net uptake. Angiotensin II also potentiated the contractile response to caffeine obtained in a Ca(++)-free buffer containing ethylene glycol bis(beta-aminoethyl ether)N,N'-tetraacetic acid (2 mM) to 148.0 +/- 4.8% of control. In both cases, the amplification was prevented by pretreatment with either staurosporine (10 nM) or calphostin C (100 nM), two inhibitors of protein kinase C. We conclude that angiotensin II potentiation of norepinephrine-induced vascular tone occurs in the absence of changes in stimulated Ca++ entry. This potentiation may be due to an increase in intracellular sensitivity to Ca++, possibly mediated by protein kinase C.
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PMID:Angiotensin II amplifies arterial contractile response to norepinephrine without increasing Ca++ influx: role of protein kinase C. 137 60

We recently reported that nitrogen dioxide (NO2), an environmental oxidant, alters the dynamics of the plasma membrane lipid bilayer structure, resulting in increased phosphatidylserine content and angiotensin II (Ang II) receptor binding. Angiotensin II is known to elicit receptor-mediated stimulation of diacylglycerol (DAG) production in pulmonary artery endothelial cells. Because protein kinase C (PKC) is a phosphatidylserine-dependent enzyme and is activated by DAG, we examined whether NO2 resulted in activation and/or translocation of PKC from predominantly cytosolic to membrane fractions of these cells. We also evaluated whether NO2 exposure resulted in increased production of DAG in pulmonary artery endothelial cells. Exposure to 5 ppm NO2 for 1-24 hr resulted in significant increases in PKC activity in the cytosolic and membrane fractions (p less than 0.05 for both fractions) compared to activities in control fractions. Exposure to Ang II resulted in translocation of PKC activity from cytosol to membrane fractions of both control and NO2-exposed cells. This translocation of PKC from cytosolic to membrane fraction was prevented by the specific receptor antagonist [Sar1 Ile8] Ang II. Exposure of 5 ppm NO2 for 1-24 hr provoked rapid increases in [3H]glycerol labeling of DAG in pulmonary artery endothelial cells. These results demonstrate that exposure to NO2 increases the production of second messenger DAG and activates PKC in both the cytosolic and membrane fractions, whereas Ang II stimulates the redistribution of PKC from cytosolic to membrane fractions of pulmonary artery endothelial cells.
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PMID:Oxidant and angiotensin II-induced subcellular translocation of protein kinase C in pulmonary artery endothelial cells. 140 42

Angiotensin II-induced phosphorylation of proteins was examined in isolated myocytes from hearts of Dahl rats. A high salt diet induced cardiac hypertrophy in Dahl salt-sensitive rats. Angiotensin II-induced phosphorylation of a 42-kd protein (pp42) was detected by two-dimensional electrophoresis in hypertrophic but not normal ventricular myocytes. Angiotensin II stimulation was time-dependent, with a peak effect at 30 minutes. The half-maximal and maximal concentrations of angiotensin II that stimulated pp42 phosphorylation were 1 and 10 nM, respectively. Phosphorylation of pp42 was a function of cardiac hypertrophy. Phorbol 12-myristate 13-acetate-induced phosphorylation of pp42 indicates the possibility of an association between protein kinase C and the signal transduction pathway of angiotensin II-induced pp42 phosphorylation. Ionomycin and A23187 (both at 1 microM) did not stimulate phosphorylation of pp42. Angiotensin II produced a small increase in the synthesis of myocyte proteins in both normal and hypertrophic cells as shown by [35S]methionine incorporation. However, this increase could not account for the increase in the phosphate content of pp42. This protein was not an isoform of actin nor was it of platelet origin. These results raise the possibility that angiotensin II may play a role in the activation of factors in hypertrophic myocytes; however, further study is required to define a link between phosphorylation of pp42 and the hypertrophic process.
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PMID:Angiotensin II-induced protein phosphorylation in the hypertrophic heart of the Dahl rat. 142 15

Phorbol 12-myristate 13-acetate (PMA), norepinephrine (NE), and contraction stimulate cardiomyocyte growth (increased protein content). Differences exist in the time course and extent of protein and RNA accumulation. Cells plated at 4 x 10(6) cells/60-mm dish and arrested with 50 mM KCl demonstrated no significant growth. Treatment with PMA stimulated growth to a maximum of 17% at 48 h. In contrast, maximal stimulation of growth was 36% at 48 h and 31% at 72 h for contracting and NE-treated cells, respectively. Maximal stimulation of the capacity for protein synthesis (RNA content) was 32% for PMA-treated cells at 24 h compared with 59% and 77% for NE-treated and contracting cells, respectively, at 72 h. In support of a primary role for altered capacity in the regulation of protein synthesis, there was a significant correlation (r = 0.84) between RNA and protein contents that was independent of the stimulus used. Angiotensin II increased RNA content by 28% at 48 h but had no effect on growth up to 72 h. Growth stimulation and increased nuclear protein kinase C (PKC) activity were induced by contraction, NE, and PMA treatment and were inhibited by staurosporine (a PKC inhibitor), suggestive of a central role for PKC.
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PMID:Acceleration of growth of cultured cardiomyocytes and translocation of protein kinase C. 151 80

Angiotensin II (Ang II) belongs to the family of the calcium-mobilizing hormones which includes other vasoactive hormones such as vasopressin, endothelin, serotonin. Angiotensin can be considered as an archetype for ligands activating the calcium messenger system. Observation of the changes occurring in the two branches of the calcium messenger system--the inositol 1, 4, 5-trisphosphate/calcium branch and the diacylglycerol/protein kinase branch--upon activation by Ang II in various target cells (adrenal zona glomerulosa cells, vascular smooth muscle cells and cardiomyocytes) emphasized common features but also revealed variation in the responses and in the interaction between the two branches (so-called cross-talk). For example, the use of single cell microfluorometry with fura-2 shows that, in adrenal glomerulosa cells, Ang II induces sinusoidal oscillations of cytosolic free calcium concentration which are typical of excitable cells; by contrast in vascular smooth muscle cells, one observes transient oscillations indicative of a mechanism of calcium-induced calcium release. Furthermore, the activation of protein kinase C by angiotensin II leads to negative feed-back mechanisms on the final biological response in adrenal cells and cardiomyocytes, whereas it has a potentiating effect in vascular smooth muscle cells. On-line video microscopy allows one to follow in real time the changes in cytosolic free calcium concentration in vascular smooth muscle cells and spontaneous beating cultured cardiomyocytes thereby revealing the spatial origin of the calcium "tide" spreading throughout the cytosol. The task is now to superimpose these calcium signals, these biochemical triggers and the framework of the cytoskeleton and intracellular organelles forming the stage of this play.
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PMID:[Transmembrane signal. Respective role of free cytosol calcium and of protein kinase C]. 182 87

We have previously shown that recombinant interleukin 1 (IL-1) and recombinant tumour necrosis factor (TNF) synergistically stimulate phospholipase A2 release from mesangial cells. We now report that treatment of mesangial cells with the beta-agonist salbutamol, prostaglandin E2 (PGE2), cholera toxin or forskolin, which all activate adenylate cyclase, increased release of phospholipase A2 activity. Likewise, addition of a membrane-permeant cyclic AMP (cAMP) analogue or the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine enhanced release of phospholipase A2 activity from mesangial cells. There was a lag period of about 8 h before a significantly enhanced secretion could be detected. Furthermore, actinomycin D or cycloheximide completely suppressed cAMP-stimulated secretion of phospholipase A2. Angiotensin II, the phorbol ester phorbol 12-myristate 13-acetate, the Ca2+ ionophore A23187 and a membrane-permeant cGMP analogue did not stimulate phospholipase A2 release from the cells. Treatment with indomethacin completely inhibited IL-1 beta- and TNF-stimulated PGE2 synthesis, without having any effect on phospholipase A2 secretion, thus excluding cytokine-induced PGE2 synthesis as the mediator of phospholipase A2 release. Neither IL-1 beta nor TNF induced any increase in intracellular cAMP in mesangial cells. Furthermore, incubation of the cells with 2',5'-dideoxyadenosine, an inhibitor of adenylate cyclase, did not block cytokine-stimulated phospholipase A2 secretion. In addition, IL-1 beta and TNF synergistically interacted with forskolin to stimulate phospholipase A2 release from the cells. The protein kinase inhibitors H-8, staurosporine, K252a and amiloride inhibited IL-1 beta- and TNF-stimulated phospholipase A2 secretion. However, high concentrations that inhibit other protein kinases were needed. These observations suggest that IL-1 beta and TNF cause secretion of phospholipase A2 by a mechanism independent of cAMP. The signalling pathways used by IL-1 beta and TNF may involve a protein kinase that is probably different from protein kinase A or protein kinase C.
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PMID:Cyclic AMP mimics, but does not mediate, interleukin-1- and tumour-necrosis-factor-stimulated phospholipase A2 secretion from rat renal mesangial cells. 184 28


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