Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: EC:3.1.3.16 (calcineurin)
17,112 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Neurons cultured from neonatal rat hypothalamus and brainstem contain many angiotensin II (Ang II) type 2 (AT2) receptors, and we previously determined that activation of these sites elicited a stimulation of serine/threonine phosphatase 2A (PP2A). Here, we have investigated the effects of Ang II on neuronal mitogen-activated protein (MAP) kinases, potential targets for PP2A. Using in-gel kinase assays and immunoprecipitation analyses we have shown that Ang II (10 nM-1 microM) elicits significant increases in p44(MAPK) (Erk1) and p42(MAPK) (Erk2) activities in cultured neurons, mediated via Ang II type 1 (AT1) receptors. This stimulatory effect of Ang II on Erk1 and Erk2 activities was potentiated by blockade of AT2 receptors with (S)-1-[4-(dimethylamino)-3-methylphenyl]methyl-5-(diphenylacetyl)- 4, 5,6,7-tetrahydro-1H-imidazo[4,5-C]pyridine-6-carboxylic acid (PD 123319, 1 microM). Furthermore, the AT2 receptor agonist N-alpha-nicotinoyl-Tyr-Lys-(N-alphaCBZ-Arg)-His-Pro-Ile-OH (CGP42112A) (10-50 nM) caused significant decreases in neuronal Erk1 and Erk2 activities, which were abolished by PD 123319 (1 microM) and by the PP2A inhibitor okadaic acid (3 nM). This indicates that AT1 and AT2 receptors have opposite actions on Erk1 and Erk2 activities in neonatal neurons. Since MAP kinases are involved in the regulation of growth/differentiation and apoptosis, our data may provide an intracellular basis for modulatory effects of Ang II receptors on these processes.
...
PMID:Mitogen-activated protein kinases in rat brain neuronal cultures are activated by angiotensin II type 1 receptors and inhibited by angiotensin II type 2 receptors. 866 75

Recent studies have suggested a role for an inhibitory G protein (Gi) and protein phosphatase 2A (PP2A) in the angiotensin II (Ang II) type 2 (AT2) receptor mediated stimulation of neuronal K+ currents. In the present study we have directly analyzed the effects of Ang II on PP2A activity in neurons cultured from newborn rat hypothalamus and brainstem. Ang II elicited time (30 min-24 h)- and concentration (10 nM -1 microM)-dependent increases in PP2A activity in these cells. This effect of Ang II involved AT2 receptors, since it was inhibited by the AT2 receptor selective ligand PD123319 (1 microM), but not by the Ang II type 1 receptor antagonist losartan (1 microM). Furthermore, the stimulatory effects of Ang II on PP2A activity were inhibited by pretreatment of cultures with pertussis toxin (PTX) (200 ng/ml; 24 h) indicating the involvement of an inhibitory G-protein; and by cycloheximide (CHX) (1 microgram/ml; 30 min) indicating a requirement for protein synthesis. These effects of Ang II appear to be via activation of PP2A, since Western Blot analyses revealed no effects of this peptide on the protein levels of the catalytic subunit of PP2A in cultured neurons. In summary, these data suggest that PP2A is a key component of the intracellular pathways coupled to neuronal AT2 receptors.
...
PMID:Angiotensin II stimulates protein phosphatase 2A activity in cultured neuronal cells via type 2 receptors in a pertussis toxin sensitive fashion. 872 1

Angiotensin II (Ang II) elicits an Ang II type 2 (AT2) receptor-mediated increase in delayed-rectifier K+ current (IK) in neurons cultured from newborn rat hypothalamus and brainstem. This effect involves a pertussis toxin (PTX)-sensitive Gi protein and is abolished by inhibition of serine and threonine phosphatase 2A (PP-2A). Here, we determined that Ang II stimulates [3H]arachidonic acid (AA) release from cultured neurons via AT2 receptors. This effect of Ang II was blocked by inhibition of phospholipase A2 (PLA2) and by PTX. Because AA and its metabolites are powerful modulators of neuronal K+ currents, we investigated the involvement of PLA2 and AA in the AT2 receptor-mediated stimulation of IK by Ang II. Single-cell reverse transcriptase (RT)-PCR analyses revealed the presence of PLA2 mRNA in neurons that responded to Ang II with an increase in IK. The stimulation of neuronal IK by Ang II was attenuated by selective inhibitors of PLA2 and was mimicked by application of AA to neurons. Inhibition of lipoxygenase (LO) enzymes significantly reduced both Ang II- and AA-stimulated IK, and the 12-LO metabolite of AA 12S-hydroxyeicosatetraenoic acid (12S-HETE) stimulated IK. These data indicate the involvement of a PLA2, AA, and LO metabolite intracellular pathway in the AT2 receptor-mediated stimulation of neuronal IK by Ang II. Furthermore, the demonstration that inhibition of PP-2A abolished the stimulatory effects of Ang II, AA, and 12S-HETE on neuronal IK but did not alter Ang II-stimulated [3H]-AA release suggests that PP-2A is a distal event in this pathway.
...
PMID:Angiotensin II type 2 receptor stimulation of neuronal delayed-rectifier potassium current involves phospholipase A2 and arachidonic acid. 942 10

The objectives of the present study were to determine whether angiotensin II (Ang II) modifies beta-adrenoceptor-induced cAMP production in preglomerular microvascular smooth muscle cells (PMVSMCs), to determine whether the Ang II/beta-adrenoceptor interaction on cAMP production differs in PMVSMCs from normotensive Wistar-Kyoto (WKY) rats vs. PMVSMCs from spontaneously hypertensive rats (SHR), and to elucidate the mechanism of Ang II/beta-adrenoceptor interactions on cAMP production in PMVSMCs. In cultured PMVSMCs, isoproterenol increased cAMP levels and this effect was markedly enhanced by Ang II. The Ang II enhancement of isoproterenol-induced cAMP was significantly greater in SHR PMVSMCs compared with WKY PMVSMCs. Neither inhibition of calcineurin with FK506, inhibition of calcium-calmodulin with W-7 and calmidazolium, nor inhibition of Gi proteins with pertussis toxin attenuated Ang II enhancement of isoproterenol-induced cAMP in PMVSMCs from either SHR or WKY rats. Moreover, the effect of Ang II on isoproterenol-induced cAMP was not mimicked by alpha-2 adrenoceptor stimulation. In contrast, chelation of intracellular calcium with BAPTA-AM attenuated, increasing intracellular calcium with A23187 augmented, and inhibition of protein kinase C with either calphostin C or chelerythrine chloride abolished Ang II enhancement of isoproterenol-induced cAMP. We conclude that in cultured PMVSMCs Ang II enhances the cAMP response to beta-adrenoceptor agonists via a mechanism that involves coincident activation of adenylyl cyclase by stimulatory G proteins and protein kinase C. Thus, protein kinase C-mediated activation of adenylyl cyclase may attenuate Ang II-induced vasoconstriction in the renal microcirculation by raising the intracellular levels of cAMP, and this mechanism may be augmented in genetic hypertension.
...
PMID:Modulation by angiotensin II of isoproterenol-induced cAMP production in preglomerular microvascular smooth muscle cells from normotensive and genetically hypertensive rats. 976 41

Ligand binding to the angiotensin II (Ang II) AT1 receptor on vascular smooth muscle cells (VSMCs) activates the Janus-activated kinase (JAK)/signal transducers and activators of transcription (STAT) pathway. We have shown previously that the JAK2 tyrosine kinase and the Src family p59 Fyn tyrosine kinase are required for Ang II-induced STAT1 tyrosine phosphorylation in VSMCs. The mitogen-activated protein kinase phosphatase, MKP-1, is required for STAT1 tyrosine dephosphorylation. In the present study, using specific enzyme inhibitors and antisense oligonucleotides, we show that Ang II-induced tyrosine phosphorylation and nuclear translocation of STAT3 in VSMCs is mediated by p60 c-Src, whereas tyrosine dephosphorylation is mediated by calcineurin. Calcineurin is activated in response to Ang II stimulation of VSMCs and is translocated to the nucleus. In addition, we show that Ang II-induced serine phosphorylation of STAT3 in VSMCs is mediated by mitogen-activated protein kinase and that dephosphorylation is mediated by protein phosphatase 2A (PP2A). PP2A translocates to the nucleus in response to Ang II stimulation of VSMCs and forms a complex with STAT3 in an Ang II-dependent manner.
...
PMID:Regulation of angiotensin II-induced phosphorylation of STAT3 in vascular smooth muscle cells. 1039 29

We are used to thinking of angiotensin (Ang) II as a regulatory hormone that stimulates constriction of vascular smooth muscle cells, aldosterone release from the adrenal gland, and sodium reabsorption in the renal tubule. We have also become accustomed to understanding that Ang II may be formed and may act locally as a chemokine that induces tyrosine phosphorylation, cell growth, hypertrophy, and differentiation. Viewing Ang II as an inflammatory molecule is stranger still. Nevertheless, recent evidence shows that Ang II is important in stimulating the production of reactive oxygen species and the activation of ancient inflammatory mechanisms. The nuclear factor kappaB (NF-kappaB) is pivotal to these processes. Activation of NF-kappaB stimulates the expression of a gene menagerie that is important to chemoattraction, expression of surface adhesion molecules, coagulation, and inflammation. In addition, Ang II has been shown to regulate cellular immune responses. It stimulates the proliferation of lymphocytes and contributes to their activation via calcineurin-related pathways. Knowledge of these mechanisms may provide additional therapeutic avenues.
...
PMID:Angiotensin, inflammation, hypertension, and cardiovascular disease. 1117 10

The present study was undertaken to observe the role of calcineurin (CaN)-dependent signaling pathway in the angiotensin II (Ang II)-induced cardiac myocyte hypertrophy. In cultured myocardial cells of neonatal rats, Ang II was used to stimulate hypertrophy and CaN-pathway blocked by CsA(an inhibitor of CaN). 3H-leucine incorporation, and activities of CaN, mitogen-activated protein kinase (MAPK) and protein kinase C (PKC) were investigated. The results showed that 3H-leucine incorporation of Ang II-stimulated myocardial cells was 46% higher than control (P < 0.01), which could be inhibited by CsA (0.5-5 micrograms/ml) and PD098059(an inhibitor of MAPK). CaN and PKC activities of Ang II-stimulated myocardial cells were 39% and 280% higher than control (P < 0.001) respectively, while no significant increase in MAPK activities was observed. CsA could reverse the increase of CaN activity, but had no effect on PKC. It is concluded that the CaN-dependent signaling pathway may play an important role in the development of the Ang II-induced cardiac myocyte hypertrophy.
...
PMID:[Involvement of calcineurin-dependent signal pathway in the angiotensin II-induced cardiac myocyte hypertrophy]. 1149 61

The present study was undertaken to observe the role of calcineurin (CaN) in the angiotensin II (Ang II) stimulated cardiac fibroblast proliferation. In cultured cardiac fibroblasts of neonatal rats, Ang II was used to stimulate proliferation while CaN was inhibited by CaN CsA inhibitor cyclosporin A (CsA). (3)H-TdR incorporation, activity of CaN and intracellular calcium concentration were measured. (3)H-TdR incorporation of Ang II stimulated fibroblasts was 72% higher than control (P<0.01), which was inhibited by CsA (0.1 10 micromol/L) in a dose dependent manner. Intracellular Ca(2+) level and CaN activity of Ang II stimulated fibroblasts were respectively 112% (P<0.01) and 17%(P<0.05) higher than control. It is concluded that CaN may play an important role in signal transduction of the Ang II induced cardiac fibroblast proliferation.
...
PMID:[Role of calcineurin in cardiac fibroblast proliferation stimulated by angiotensin II]. 1195 Nov 12

Trophoblast implantation depends, in part, on the controlled production of plasmin from plasminogen, a process regulated by plasminogen activators and plasminogen activator inhibitors. We have determined that angiotensin II (Ang II) stimulates plasminogen activator inhibitor-1 (PAI-1) synthesis and secretion in human trophoblasts in a time- and concentration-dependent manner. Our results indicate that Ang II activates PAI-1 gene expression through the AT1 receptor and involves the calcium-dependent activation of calcineurin and the nuclear translocation of NFAT. Increased PAI-1 synthesis and secretion is associated with reduced trophoblast invasion as judged by an in vitro invasion assay. These studies are the first to link the renin-angiotensin system with the fibrinolytic system to regulate trophoblast invasion.
...
PMID:Angiotensin II inhibits human trophoblast invasion through AT1 receptor activation. 1198 98

It is well known that angiotensin II (Ang II) is implicated in the phenotypic modulation and hypertrophy of vascular smooth muscle cells (VSMCs). To study the mechanisms by which Ang II contributes to the pathological changes of VSMCs, we examined whether Ang II stimulated myocyte enhancer factor 2 (MEF2)- and calcineurin/nuclear factor of activated T cell (NFAT)-dependent transcriptional activation of genes in VSMCs. Ang II increased the DNA binding activity of MEF2A and its expression at the protein level. Ang II induced c-jun promoter activity, and this increase was inhibited by dominant-negative mutants of MEF2A and mitogen-activated protein kinase kinase 6 but not by calcineurin inhibitors. Ang II stimulated NFAT DNA binding activity and NFAT-dependent gene transcription, and these effects of Ang II were inhibited by calcineurin inhibitors. Furthermore, Ang II induced the promoter activity of the nonmuscle-type myosin heavy chain B gene, which we used as a marker of the dedifferentiated state of VSMCs, and this increase was inhibited by calcineurin inhibitors but not by the dominant-negative mutants of MEF2A or mitogen-activated protein kinase kinase 6. Finally, Ang II increased protein synthesis, and this increase was inhibited by infection with an adenovirus construct that expresses the dominant-negative mutant of MEF2A but not by calcineurin inhibitors. These results suggest that Ang II stimulates the MEF2- and calcineurin/NFAT-dependent pathways and that these pathways have distinct roles in VSMCs.
...
PMID:Angiotensin II induces myocyte enhancer factor 2- and calcineurin/nuclear factor of activated T cell-dependent transcriptional activation in vascular myocytes. 1201 67


1 2 3 4 5 6 Next >>

---