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:2.7.11.13 (protein kinase C)
49,245 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Activity-dependent neuronal gene expression is thought to require activation of L-type calcium channels, a view based primarily on studies in which chronic potassium (K(+)) depolarization was used to mimic neuronal activity. However, N-type calcium channels are primarily inactivated during chronic depolarization, and their potential contribution to gene expression induced by physiological patterns of stimulation has not been defined. In the present study, electrical stimulation of dissociated primary sensory neurons at 5 Hz, or treatment with elevated K(+), produced a large increase in the percentage of neurons that express tyrosine hydroxylase (TH) mRNA and protein. However, blockade of L-type channels, which completely inhibited K(+)-induced expression, had no effect on TH expression induced by patterned stimulation. Conversely, blockade of N-type channels completely inhibited TH induction by patterned stimulation, whereas K(+)-induced expression was unaffected. Similar results were obtained for depolarization-induced expression of the immediate early genes Nurr1 and Nur77. In addition, TH induction by patterned stimulation was significantly reduced by inhibitors of PKA and PKC but was unaffected by inhibition of the mitogen-activated protein kinase (MAPK) pathway. On the other hand, K(+)-induced TH expression was significantly reduced by inhibition of the MAPK pathway but was unaffected by inhibitors of PKA or PKC. These results demonstrate that N-type calcium channels can directly link phasic membrane depolarization to gene expression, challenging the view that activation of L-type channels is required for nuclear responses to physiological patterns of activity. Moreover, our data show that phasic and chronic depolarizing stimuli act through distinct mechanisms to induce neuronal gene expression.
...
PMID:Physiological patterns of electrical stimulation can induce neuronal gene expression by activating N-type calcium channels. 1130 10

In neurons, pituitary adenyl cyclase activating peptide (PACAP) stimulates signaling cascades, involving cAMP and calcium. PACAP appears to play a role in up-regulation of tyrosine hydroxylase and dopamine beta-hydroxylase via protein kinase C and/or protein kinase A. Furthermore, the PACAP gene (ADCYAP1) is located in chromosome 18p11, where linkage of bipolar disorders and schizophrenia has been reported. In this study, we scanned the coding region of the PACAP gene for mutations in 24 Japanese patients with schizophrenia and 24 Japanese patients with bipolar disorders. No variant in the coding region was found. One polymorphism, INV3-37A/T, in the third intron was detected. Case-control comparisons revealed no significant association between this polymorphism and schizophrenia or bipolar disorders. This study did not provide evidence for the contribution of the PACAP gene to the etiology of schizophrenia or bipolar disorders in the Japanese population.
...
PMID:Association analysis of the pituitary adenyl cyclase activating peptide gene (PACAP) on chromosome 18p11 with schizophrenia and bipolar disorders. 1151 50

We have previously shown that murine recombinant leptin directly stimulates catecholamine synthesis through the long form of the leptin receptor (Ob-Rb) expressed in cultured porcine chromaffin cells. Additionally, we found that leptin activates IP3 production after PLC activation. It is well established that activation of PLC elicits IP3 production as well as an increase in diacylglycerol, a compound that stimulates PKC. Therefore, we investigated the involvement of PKC in leptin-induced catecholamine synthesis. Leptin was found to induce significant increases in PKC activity in a dose-dependent manner (1, 10, and 100 nM); chelation of extracellular Ca(2+) by EDTA abolished this PKC stimulatory activity. We also confirmed by Western blot analysis that leptin (at 100 nM) induced significant increases in Ca(2+)-dependent PKC alpha, -beta(I), and -gamma expression. The activity of the rate-limiting enzyme tyrosine hydroxylase (TH) in the biosynthesis of catecholamine is regulated at the transcriptional and posttranscriptional levels. TH enzyme activity and TH mRNA levels induced by 100 nM leptin were significantly inhibited by the PKC inhibitor Ro 32-0432 as well as by EDTA. In addition, increases in TH protein and intracellular catecholamine content stimulated by leptin were completely inhibited by Ro 32-0432. Leptin markedly activated ERKs and, to a lesser extent, JNK; these stimulatory effects on ERKs and JNK were completely inhibited by Ro 32-0432 as well as EDTA. In contrast, leptin did not activate P38 MAPK. Similar to leptin, PMA activated ERK and JNK. Nicardipine and omega-conotoxin GVIA, each at 1 microM, were effective at inhibiting leptin-induced TH enzyme activity, TH mRNA accumulation, PKC activity, and ERK activity. Leptin increased activating protein-1 DNA-binding activity, and this was diminished by Ro 32-0432 as well as EDTA, similar to the reduction of TH mRNA levels. In addition, using supershift analysis, we documented the involvement of c-Fos and, to a lesser extent, c-Jun in leptin-induced activating protein-1 activity. These results indicate that leptin stimulates Ca(2+)-dependent PKC isoform-dependent catecholamine synthesis in porcine chromaffin cells. Previously, we had shown that leptin stimulated cAMP. The present study also showed that H89 (a PKA inhibitor) moderately, but significantly, inhibited leptin-induced ERK and TH mRNA. Consistent with this finding, leptin is shown here to activate novel PKC epsilon, which is assumed to stimulate Raf, upstream of ERKs, via cAMP, supporting the suggestion that Ca(2+)-independent novel PKC may also play some physiological role in regulating catecholamine synthesis.
...
PMID:Leptin stimulates catecholamine synthesis in a PKC-dependent manner in cultured porcine adrenal medullary chromaffin cells. 1160 54

We previously showed that CGP 42112 (an angiotensin type 2 [AT(2)] agonist) markedly reduces catecholamine biosynthesis by decreasing cGMP production mediated by AT(2), a subtype of Ang II receptor that is dominantly expressed in cultured porcine chromaffin cells. To elucidate the relationship of the 2 types of Ang II receptors, angiotensin type 1 (AT(1)) and AT(2), in the synthesis of catecholamine in adrenal medullary cells, we have examined the effect of Ang II plus CV-11974 (an AT(1) antagonist that selectively simulates AT(2) stimulation) and the effect of Ang II plus PD 123319 (an AT(2) antagonist that selectively simulates AT(1) stimulation) on catecholamine synthesis. We found that Ang II reduced cGMP production via AT(2), in a similar manner to that found with CGP 42112. Stimulation of AT(1) significantly upregulated protein kinase C activity. Tyrosine hydroxylase (TH) is a rate-limiting enzyme involved in the biosynthesis of catecholamine, and this catecholamine synthesis depends both on TH enzyme activity and on the levels of TH protein after TH gene transcription. We found that AT(2) stimulation significantly inhibited TH enzyme activity, whereas AT(1) stimulation significantly upregulated TH enzyme activity. The stimulatory effect of AT(1) was completely inhibited by Ro-32-0432 (a protein kinase C inhibitor) and PD 98059 (a MAP kinase kinase-1 [MEK-1] inhibitor). Pretreatment of cells with either 8-Br-cGMP (a membrane-permeable cGMP analog) or Zaprinast (a phosphodiesterase inhibitor) abolished the inhibitory effect of AT(2) on TH enzyme activity, indicating that the stimulatory effect of AT(2) may be mediated through a reduction in cGMP concentration. Similar to the effect on TH enzyme activity, AT(2) stimulation significantly reduced TH mRNA and protein levels and net catecholamine content below basal levels, whereas AT(1) stimulation increased them. We confirmed these findings by gel mobility shift assay. Our results show that stimulation of AT(2) reduces catecholamine biosynthesis via a decrease in cGMP levels. In contrast, stimulation of AT(1) stimulates catecholamine biosynthesis through activation of PKC. Thus, we conclude that AT(1) and AT(2) have counter-regulatory roles in the synthesis of catecholamine in adrenal medullary chromaffin cells.
...
PMID:Angiotensin II type 2 receptor counter-regulates type 1 receptor in catecholamine synthesis in cultured porcine adrenal medullary chromaffin cells. 1179 93

We have studied the effects of dopamine and the D2-like agonist quinpirole on calcium currents of neurons isolated from the striatum and the globus pallidus (GP). Experiments were performed in young adult rats, either in control conditions or following lesion of the nigrostriatal pathway by the unilateral injection of 6-hydroxydopamine (6-OHDA) in the substantia nigra. Apomorphine-driven contralateral turning, 15 days after lesioning, assessed the severity of the dopamine denervation. In addition, the loss of tyrosine hydroxylase immunohistochemistry confirmed the extent of the toxin-induced damage. In both striatal medium spiny (MS) and GP neurons of control animals dopamine and quinpirole promoted a very modest inhibition of calcium conductance. Following 6-OHDA, the inhibition was unaltered in MS (from 10 to 12%), but significantly augmented in GP neurons (21% vs. 9%). Interestingly, analogous inhibition was observed in GP neurons dissociated 20 h after reserpine treatment. Further features of the D2 response were thus studied only in neurons isolated from 6-OHDA-lesioned GP. The D2 modulation was G-protein-mediated but not strictly voltage-dependent. omega-Conotoxin-GVIA occluded the response implying the involvement of N-type calcium channels. The effect of quinpirole developed fast and was insensitive to alterations of cytosolic cAMP. The incubation in phorbol esters or OAG blocked the D2 effect, supporting the involvement of PKC. These findings suggest that postsynaptic D2-like receptors are functionally expressed on GP cell bodies and may supersensitize following dopamine-denervation. A direct D2 modulation of calcium conductance in GP may alter GP firing properties and GABA release onto pallidofugal targets.
...
PMID:D2-mediated modulation of N-type calcium currents in rat globus pallidus neurons following dopamine denervation. 1190 23

It has been reported that endothelins (ETs) stimulate catecholamine release from chromaffin cells. However, it is not known whether ETs also affect catecholamine biosynthesis. Thus, using a rat pheochromocytoma cell line, PC12, we examined the effects of ETs on catecholamine biosynthesis. The mRNA level and activity of tyrosine hydroxylase (TH), a rate-limiting enzyme in catecholamine biosynthesis, were increased significantly by endothelin-1 (ET-1) (100nM). These stimulatory effects were inhibited completely by a blocker for the A-type endothelin receptor, BQ-123 [cyclo(D-alpha-aspartyl-L-prolyl-D-valyl-L-leucyl-D-tryptophyl)] (1 microM), but not by a blocker for the B-type endothelin receptor, BQ-788 (N-cis 2,6-dimethylpiperidinocarbonyl-L-gamma-methylleucyl-D-1-methoxycarbonyltryptophanyl-D-norleucine (1 microM). Also, Ro-32-0432 (3-[8-[(dimethylamino)methyl]-6,7,8,9-tetrahydropyrido-[1,2-a]indol-10-yl]-4-(1-methyl-3-indolyl)-H-pyrrole-2,5-dione hydrochloride) (100nM), a protein kinase C inhibitor, completely inhibited ET-1-induced increases in TH activity and mRNA level. Furthermore, ET-1 (100nM) significantly stimulated protein kinase C activity, as well as inositol 1,4,5-triphosphate production; these stimulatory effects were abolished by BQ-123 but not by BQ-788. Moreover, ET-1 (100nM) significantly increased both the TH-protein level and the intracellular catecholamine content. By contrast to ET-1, endothelin-3 did not affect catecholamine synthesis. These results indicate that ET-1, but not ET-3, stimulates catecholamine synthesis through the PKC pathway in PC12 cells. Also, the use of selective ET receptor antagonists suggests that the effects of ET-1 on catecholamine biosynthesis are mediated through ET(A).
...
PMID:Stimulation of catecholamine biosynthesis via the protein kinase C pathway by endothelin-1 in PC12 rat pheochromocytoma cells. 1191 50

Hypoxia and ischemia regulate the expression of several important genes at the level of transcription and of mRNA stability. Two isoforms of a 40-kDa poly(C)-binding protein, previously identified as RNA-binding proteins, bind to a hypoxia-inducible protein-binding site in the 3'-untranslated region of erythropoietin and tyrosine hydroxylase mRNAs and regulate mRNA stability. To determine if poly(C)-binding proteins show changes in expression -- which might regulate mRNA stability -- in hypoxic or ischemic neuronal cells, we examined poly(C)-binding protein 1 and poly(C)-binding protein 2 expression in hypoxic cortical neuron cultures and in rat cerebral cortex after focal ischemia. Reverse transcription-polymerase chain reaction and western blotting showed hypoxic up-regulation of poly(C)-binding protein 1, and down-regulation of poly(C)-binding protein 2, mRNA and protein expression. Hypoxia-inducible expression of poly(C)-binding protein 1 was mediated by p38 mitogen-activated protein kinase, while hypoxia-reducible expression of poly(C)-binding protein 2 was mediated by protein kinase C. Immunostaining showed that poly(C)-binding protein 1, but not poly(C)-binding protein 2, expression was increased in the ischemic boundary zone (penumbra) of the frontal cortex after 90 min of ischemia, and persisted for at least 72 h after reperfusion. These results demonstrate that poly(C)-binding protein 1 and poly(C)-binding protein 2 in cortical neurons are differentially affected by hypoxic/ischemic insults, suggesting that there are functional differences between poly(C)-binding protein isoforms. Since we observed no poly(C)-binding protein expression in astroglia, alternative mRNA stability mechanisms may exist in these cells.
...
PMID:Expression of poly(C)-binding proteins is differentially regulated by hypoxia and ischemia in cortical neurons. 1195 62

Although it is now established that immunocompetent cells produce catecholamines (CA), which in turn may act as autocrine/paracrine mediators, little is known about the mechanisms regulating CA production in these cells. In the present study, evidence is provided that stimulation of human cultured peripheral blood mononuclear cells (PBMCs) with phytohaemagglutinin (PHA) induces the expression of tyrosine hydroxylase (TH) mRNA and subsequently increases intracellular CA levels through protein kinase C (PKC) activation and the contribution of intracellular Ca(++)-dependent mechanisms. Increased production of CA in PHA-stimulated PBMCs suggests a preferential involvement of catecholaminergic pathways in the functional modulation of activated cells. These findings may help to better define the role of immunocompetent cell-derived CA in the neuroimmune network.
...
PMID:Stimulation with phytohaemagglutinin induces the synthesis of catecholamines in human peripheral blood mononuclear cells: role of protein kinase C and contribution of intracellular calcium. 1196 Jun 48

In the retina, somatostatin (SRIF) acts as a neuromodulator by interacting with specific SRIF subtype (sst) receptors. The aim of this study was to detect mRNAs for sst(1-5) receptors by semiquantitative RT-PCR and to determine the cellular localization of either SRIF or individual SRIF receptor immunoreactivities. Size, density and absolute number of immunolabeled somata were measured using computer-assisted image analysis. With RT-PCR we found that all five sst receptor mRNAs were expressed, with highest levels of sst(2) and sst(4) receptors. SRIF immunolabeling was localized to sparse-occurring amacrine cells in the inner nuclear layer (INL) and to displaced amacrine cells in the ganglion cell layer (GCL). sst(2A) receptors were localized to protein kinase- (PKC) immunoreactive (IR) rod bipolar cells, calbindin- (CaBP-) IR horizontal cells, tyrosine hydroxylase- (TH-) IR amacrine cells and glycinergic amacrine cells. None of the sst(2A)-IR amacrine cells were found to express parvalbumin (PV) immunoreactivity. sst(4) receptor immunolabeling was localized to CaBP-IR and CaBP-non-IR cells in the GCL that originated long process bundles in the GC axon layer. These cells were not observed after optic nerve transection and they were therefore interpreted as ganglion cells. Quantitative analysis showed that all of the PKC-IR rod bipolar cells, CaBP-IR horizontal cells, and TH-IR amacrine cells and 5% of the glycinergic amacrine cells expressed sst(2A) receptors. In addition, 4-6% of the putative ganglion cells expressed sst(4) receptors. The localization of SRIF to sparse-occurring retinal neurons, together with the widespread expression of sst(2A) and sst(4) receptors suggests that SRIF acts at multiple levels of retinal circuitry. These results provide a database for investigations of the functional retinal networks in mice with genetic alterations of somatostatinergic transmission.
...
PMID:Somatostatin (SRIF) and SRIF receptors in the mouse retina. 1198 24

The integrative nuclear FGFR1 signaling (INFS) pathway functions in association with cellular growth, differentiation, and regulation of gene expression, and is activated by diverse extracellular signals. Here we show that stimulation of angiotensin II (AII) receptors, depolarization, or activation protein kinase C (PKC) or adenylate cyclase all lead to nuclear accumulation of fibroblast growth factor 2 (FGF-2) and FGFR1, association of FGFR1 with splicing factor-rich domains, and activation of the tyrosine hydroxylase (TH) gene promoter in bovine adrenal medullary cells (BAMC). The up-regulation of endogenous TH protein or a transfected TH promoter-luciferase construct by AII, veratridine, or PMA (but not by forskolin) is abolished by transfection with a dominant negative FGFR1TK-mutant which localizes to the nucleus and plasma membrane, but not by extracellularly acting FGFR1 antagonists suramin and inositolhexakisphosphate (IP6). Mechanism of TH gene activation by FGF-2 and FGFR1 was further investigated in BAMC and human TE671 cultures. TH promoter was activated by co-transfected HMW FGF-2 (which is exclusively nuclear) but not by cytoplasmic FGF-1 or extracellular FGFs. Promoter transactivation by HMWFGF-2 was accompanied by an up-regulation of FGFR1 specifically in the cell nucleus and was prevented FGFR1(TK-) but not by IP6 or suramin. The TH promoter was also transactivated by co-transfected wild-type FGFR1, which localizes to both to the nucleus and the plasma membrane, and by an exclusively nuclear, soluble FGFR1(SP-/NLS) mutant with an inserted nuclear localization signal. Activation of the TH promoter by nuclear FGFR1 and FGF-2 was mediated through the cAMP-responsive element (CRE) and was associated with induction of CREB- and CBP/P-300-containing CRE complexes. We propose a new model for gene regulation in which nuclear FGFR1 acts as a mediator of CRE transactivation by AII, cell depolarization, and PKC.
...
PMID:Integrative nuclear FGFR1 signaling (INFS) pathway mediates activation of the tyrosine hydroxylase gene by angiotensin II, depolarization and protein kinase C. 1206 59


<< Previous 1 2 3 4 5 6 7 8 9 10

---