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

Myristoylated alanine-rich C-kinase substrate (MARCKS) and F1/GAP-43 (B-50/neuromodulin) are both major specific substrates for protein kinase C (PKC) and appear to play an important role in the regulation of neuroplastic events during development and in the adult brain. Since PKC isozymes are differentially expressed in brain and the expression of F1/GAP-43 and MARCKS are differentially regulated by PKC through posttranslational mechanisms, the present study examined the relative distribution of both mRNAs in the adult brain by using in situ hybridization histochemistry. MARCKS hybridization was most pronounced in the olfactory bulb, piriform cortex (layer II), medial habenular nucleus, subregions of the amygdala, specific hypothalamic nuclei, hippocampal granule cells, neocortex, and cerebellar cortex, intermediate in the superior colliculus, hippocampal CA1, and certain brainstem nuclei including the locus coeruleus, and low-absent in regions of the caudate-putamen, geniculate, thalamic nuclei, lateral habenular nucleus, and hippocampal CA3 pyramidal and hilar neurons. Consistent with previous reports, prominent F1/GAP-43 hybridization was observed in neocortex, medial geniculate, piriform cortex (layer II), substantia nigra pars compacta, hippocampal CA3 pyramidal cells, thalamic and hypothalamic nuclei, lateral habenular nucleus, locus coeruleus, raphe nuclei, and cerebellar granule cells, intermediate in regions of the thalamus, hypothalamus, and amygdala, and low-absent in regions of the olfactory bulb, caudate-putamen, medial habenular nucleus, hippocampal granule cells, and superior colliculus. Overall, F1/GAP-43 was highly expressed in a greater number of regions compared to MARCKS and, in a number of regions, including the hippocampus, habenular complex, ventral tegmentum, geniculate, and certain brain stem nuclei, a striking inverse pattern of expression was observed. These results indicate that MARCKS gene expression, like that of F1/GAP-43, remains elevated in select regions of the adult rat brain which are associated with a high degree of retained plasticity. The potential role of PKC in the regulation of MARCKS and F1/GAP-43 gene expression in brain is assessed.
 ...
PMID:Comparative distribution of myristoylated alanine-rich C kinase substrate (MARCKS) and F1/GAP-43 gene expression in the adult rat brain. 905 12

We investigated the effects of age and nitric oxide synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME), on protein kinase C (PKC), adenylyl cyclase, calcium/calmodulin-independent cyclic-AMP phosphodiesterase (cyclic-AMP PDE) and voltage-dependent L-type calcium channels in Fischer rat brain using autoradiography. [3H]Phorbol 12,13-dibutyrate (PDBu), [3H]forskolin, [3H]rolipram and [3H]PN200-110 were used to label PKC, adenylyl cyclase, cyclic-AMP PDE and calcium channels, respectively. [3H]Forskolin binding significantly decreased in the striatum, hippocampal CA3 sector, dentate gyrus, hilus, thalamus, substantia nigra and cerebellum of 24-month-old (aged) rats, as compared with 6-month-old (adult) animals. [3H]Rolipram binding also showed an age-related reduction in the thalamus and cerebellum in rats. In contrast, no age-related changes were observed in [3H]PDBu and [3H]PN200-110 binding in the rat brain. Chronic treatment with L-NAME (5 mg/kg, once a day for 4 weeks) showed no significant changes in [3H]PDBu, [3H]rolipram and [3H]PN200-110 binding in aged rat brains. However, this treatment significantly increased age-related decreases in [3H]forskolin binding in the frontal cortex; striatum and hippocampal CA1 sector in rats. The results demonstrate that [3H]forskolin binding in the rat brain is more susceptible to aging processes than [3H]PDBu, [3H]rolipram and [3H]PN200-110 binding. Furthermore, our study shows that chronic treatment with NO inhibitor increases the age associated changes in [3H]forskolin binding in most brain areas of aged rats. These findings suggest that NO may play a key role in the regulation of adenylyl cyclase system during aging processes.
 ...
PMID:Effect of nitric oxide synthase inhibitor on age-related changes in second messenger systems and calcium channels in rats. 910 40

The modulation of high-threshold Ca current (I(Ca)) by adenosine receptors was studied using the voltage clamp method on acutely dissociated guinea pig hippocampal CA3 pyramidal neurons. When these neurons were exposed to adenosine in the presence of A1, A2a and A2b receptor antagonists, I(Ca) potentiation occurred at test potentials of -10 mV, but not at -40 mV. Similar potentiation also occurred using the A3 agonist N6-2-(4-aminophenyl)ethyl-adenosine (APNEA), either alone or in the presence of A1 and A2 antagonists. The putative A4 agonist 2-phenylaminoadenosine (CV-1808; Cornfield et al., 1992) did not potentiate I(Ca) at four concentrations tested between 25 nM and 2500 nM. K0.5 for the APNEA-induced potentiation was 25.4 nM, comparable to that determined in binding studies for the cloned receptor (15.5 nM; Zhou et al., 1992). I(Ca) potentiation by APNEA was blocked by intracellular application of WIPTIDE, a PKA inhibitor (p < 0.001), but was not affected by protein kinase C (PKC) inhibitor peptide (19-36). These results indicate that: (1) A3 receptor activation can significantly potentiate I(Ca), and (2) because the A3 receptor has been linked to down-regulation of adenylyl cyclase (Zhou et al., 1992), PKA appears to be negatively coupled to I(Ca).
 ...
PMID:Adenosine A3 receptors potentiate hippocampal calcium current by a PKA-dependent/PKC-independent pathway. 917 14

The present study demonstrates cell-specific and developmental regulation of 5' and 3' splicing of the N-methyl-D-aspartate receptor NR1 subunit within specific neuronal populations of the hippocampus. At birth, NR1 transcripts lacking exon 5 (encoding the amino-terminal splice cassette N1) exhibit mature patterns of labelling within the hippocampus, with high levels of expression in the CA1, CA3, and dentate gyrus. In contrast, exon 5-containing (NR1(1XX)) transcripts are expressed at low levels until P8, at which time expression is prominent and essentially uniform in the CA1, CA3, and dentate gyrus. Exon 5 expression increases at a faster rate in CA3 than in CA1 or dentate gyrus. By the third week postnatal (postnatal day P21), exon 5-containing transcripts exhibit a distinct gradient of labelling, with more intense expression in CA3, than in CA1 or dentate gyrus. By P21 pyramidal neurons of the CA1 and granule cells of the dentate gyrus express mainly NR1(0XX) receptor messenger RNAs (lacking exon 5). Because splicing in of the N1 splice cassette confers greater current amplitude and enhanced potentiation by protein kinase C, these observations predict elevated levels of synaptic activity in the CA1 early in postnatal life, a time at which synaptic plasticity is enhanced. The carboxy-terminal splice cassettes C1 and C2 are regulated independently within the hippocampus. Whereas NR1(X11) (C1-, C2-containing) and NR1(X01) (C2 only) receptors exhibit high levels of expression in CA1, CA3, and dentate gyrus, NR1(X00) receptors are expressed more intensely in pyramidal neurons of CA3. NR1(X10) receptor expression is very low in all cells and at all times examined, even in adults. Because splicing in of the C1 cassette is thought to regulate receptor targeting, clustering, and cytoskeletal interactions, N-methyl-D-aspartate receptors in the two hippocampal subfields may play differing roles in synaptogenesis and the formation of new neuronal contacts. Moreover, cell-specific patterns of NR1(X11) receptor messenger RNAs parallel those of NR1(0XX) receptor messenger RNAs; and cell-specific patterns of NR1(1XX) (N1-containing) receptor messenger RNAs parallels those of NR1(X00) (C1-, C2-lacking) receptor messenger RNAs throughout development. These observations suggest that NR1(100) receptors, which exhibits the greatest potentiation by protein kinase C, are likely to be important in CA1 during the second and third weeks postnatal. Cell-specific expression of NR1 splice variants undoubtedly contributes to functional diversity of N-methyl-D-aspartate receptor properties in neuronal populations within the hippocampus. Developmental regulation of NR1 splicing is likely to influence synaptic plasticity and the formation of new synaptic contacts. Moreover, findings from this study suggest that a change in NR1 splicing following a neurological injury could significantly alter glutamate pathogenicity in a particular population of cells.
 ...
PMID:Developmental regulation and cell-specific expression of N-methyl-D-aspartate receptor splice variants in rat hippocampus. 920 Jul 24

An immunocytochemical examination of the rabbit hippocampus was done to determine which of the Ca(2+)-dependent protein kinase C (PKC) isoforms (PKC alpha, -beta I, -beta II, or -gamma) are involved in associative learning. The hippocampally dependent trace eyeblink conditioning task was used for behavioral training, and pseudoconditioned and naive animals served as controls. Significant increases (P < 0.05) in staining intensity were found with antibodies reactive with the catalytic or the regulatory domain of PKC gamma in conditioned animals compared with naive and pseudoconditioned subjects at a 24-h post-conditioning time point. The increase was found in CA1 and CA3 pyramidal cell bodies, in apical dendrites and the proximal part of the basilar dendrites, and in cell bodies of dentate granule cells. In contrast, no conditioning-specific changes were found for PKC alpha, -beta I, or -beta II in in hippocampal neurons. The increase in PKC gamma immunoreactivity (ir) was significantly less (P < 0.05) in poor learners than in good learners. The correlation between the degree of PKC gamma-ir and the total number of conditioned responses across training sessions was both positive and significant. These results suggest that PKC gamma is the major Ca(2+)-dependent PKC isoform involved in hippocampal neurons during acquisition of associative memories. Immunoblots revealed no conditioning-induced increase in the total amount or translocation of PKC gamma at the 24-h time point, and no proteolytic PKC fragments were observed. In agreement with the Western blot data, PKC activity did not differ among naive, pseudoconditioned, and trace conditioned animals. The conditioning-induced increase in antibody binding to the gamma-isoform must therefore be due to an increased access to the antigenic site(s) as a result of alteration in the tertiary structure of PKC gamma or in quaternary interactions of PKC gamma in situ.
 ...
PMID:gamma Isoform-selective changes in PKC immunoreactivity after trace eyeblink conditioning in the rabbit hippocampus. 922 25

Selective activation of second messenger pathways were tested on presynaptic metabotropic glutamate receptor action at mossy fibre-CA3 synapses, using a rat hippocampal slice preparation. Application of the protein kinase C activator, phorbol 12,13-diacetate, or the adenylate cyclase activator, forskolin, markedly enhanced the mossy fibre field excitatory postsynaptic potentials, and suppressed the relative magnitude of the synaptic depression induced by (2S,1'R,2'R,3'R)-2-(2,3-dicarboxycyclopropyl)glycine, an agonist at group-II metabotropic glutamate receptors. These effects were also observed in a low Ca2+ solution, suggesting that they were not due to saturation of transmitter release process. Inactive analogues of the respective activators (4alpha-phorbol 12,13-didecanoate and 1,9-dideoxyforskolin) neither enhanced the mossy fibre responses nor suppressed (2S,1'R,2'R,3'R)-2-(2,3-dicarboxycyclopropyl)glycine-induced synaptic depression. These results suggest that the presynaptic inhibitory action of group-II metabotropic glutamate receptors at mossy fibre-CA3 synapses could be negatively regulated by protein kinase C- and cyclic AMP-dependent mechanisms.
 ...
PMID:Phorbol ester and forskolin suppress the presynaptic inhibitory action of group-II metabotropic glutamate receptor at rat hippocampal mossy fibre synapse. 925 23

Previous reports have demonstrated a striking increase of the immunoreactivity of the gamma-isoform of protein kinase C (PKCgamma-ir) in Ammon's horn and dentate gyrus (DG) of rodent hippocampus after training in a spatial orientation task. In the present study, we investigated how 8 days of psychosocial stress affects spatial discrimination learning in a hole board and influences PKCgamma-ir in the hippocampal formation. The acquisition of both reference memory and working memory was significantly delayed in the stressed animals during the entire training period. With respect to cellular plasticity, the training experience in both nonstressed and stressed groups yielded enhanced PKCgamma-ir in the CA1 and CA3 regions of the posterior hippocampus but not in subfields of the anterior hippocampus. Stress enhanced PKCgamma-ir in the DG and CA3 pyramidal cells of the anterior hippocampus. In stressed animals that were subsequently trained, the PKCgamma-ir was increased in the posterior CA1 region to the same level as that found in nonstressed trained animals. Stress apparently abrogated the PKCgamma-ir training response in the CA3 region. In a second experiment, the elevation of plasma corticosterone levels to values that are found during stress did not significantly influence reference memory scores but slightly and temporarily affected working memory. The training-induced enhancement of PKCgamma-ir in the CA1 region was similar in trained and corticosterone-treated trained animals, but the learning-induced PKCgamma-ir response in the posterior CA3 area was absent after corticosterone pretreatment. These results reveal that prolonged psychosocial stress causes spatial learning deficits, whereas artificial elevation of corticosterone levels to the levels that occur during stress only mildly affects spatial memory performance. The spatial learning deficits following stress are reflected only in part in the redistribution of hippocampal PKCgamma-ir following training.
 ...
PMID:Exposure to chronic psychosocial stress and corticosterone in the rat: effects on spatial discrimination learning and hippocampal protein kinase Cgamma immunoreactivity. 928 82

Kainate-induced seizure activity causes persistent changes in the hippocampus that include synaptic reorganization and functional changes in the mossy fibers. Using in situ hybridization histochemistry, the expression of PKC alpha, PKC beta, PKC gamma, PKC delta and PKC epsilon mRNAs was investigated in the hippocampus of adult rats following seizures induced by a s.c. injection of kainic acid. In CA1 and CA3, we found a significant decrease in PKC gamma mRNA 1 day after kainic acid which persisted for a 2nd day in CA1. None of the other PKC isoform mRNAs were altered in CA1 or CA3. In granule cells, a significant up-regulation specific to PKC epsilon mRNA was observed. One week after kainic acid administration, a marked increase in PKC epsilon immunoreactivity was found that persisted 2 months after kainic acid administration. PKC epsilon immunoreactivity was found associated with mossy fibers projecting to the hilus of the dentate gyrus and to the stratum lucidum of the CA3 field and presumably with the newly sprouted mossy fibers projecting to the supragranular layer. These data provide the first evidence for a long-lasting increase of the PKC epsilon in the axons of granule cells caused by kainate-induced seizures and suggest that PKC epsilon may be involved in the functional and/or structural modifications of granule cells that occur after limbic seizures.
 ...
PMID:Selective up-regulation of protein kinase C epsilon in granule cells after kainic acid-induced seizures in rat. 938 78

These studies were designed to examine the effect of chronic administration of pentobarbital on activity of adenylate cyclase (AC) and protein kinase C (PKC) in the rat brain by autoradiography. Recently, it has been suggested that the phosphorylation of specific proteins may be involved in the development of physical dependence. An experimental model of barbiturate tolerance and dependence was developed using i.c.v. infusion of pentobarbital (300 microg/10 microl/hr for 7 days) by osmotic minipumps and abrupt withdrawal from pentobarbital. The levels of [3H]forskolin binding were elevated (28-67%) in cortex, thalamus, dentate gyrus, hippocampal CA3 and cerebellum of the pentobarbital withdrawal animals, while these changes were not observed in tolerant rats. The levels of [3H]phorbol dibutyrate binding were highly elevated (38-65%) in the region of cortex, caudate putamen, septum, thalamus, dentate gyrus, and cerebellum of rats withdrawal from pentobarbital. These results show that the levels of AC and PKC were significantly elevated in pentobarbital withdrawal rats, and suggest that the levels of AC and PKC are altered in a region-specific manner during pentobarbital withdrawal.
 ...
PMID:Changes in [3H]forskolin binding to adenylate cyclase and [3H]phorbol dibutyrate binding to protein kinase C in pentobarbital tolerant/dependent rats. 956 79

The myristoylated alanine-rich C kinase substrate (MARCKS) and MARCKS-related protein (MRP) are both membrane-associated phosphoproteins that interact with calmodulin and filamentous actin in a protein kinase C phosphorylation-dependent manner. In the present study, we examined MARCKS and MRP gene expression in the postnatal (P) rat brain (1, 7, 14, 21, and 90 days after birth) by using quantitative in situ hybridization. At P1, MRP expression was high in neocortex, striatum, thalamus, cerebellar cortex, and hippocampus (CA1-CA3, hilus, and granule cell layer) but low in brainstem and, between P7 and P14, exhibited a dramatic decline in each of these regions except hippocampal CA1 and granule cell layers. Between P14 and P21, MRP expression increased in white matter regions including the corpus callosum, fimbria/fornix, and cerebellar deep white matter. At P90 (adult), MRP remained strongly expressed in the olfactory bulb, medial habenula, hippocampal CA1, and the inner two-thirds of granule cell layer, temporal, and entorhinal cortices, the corpus callosum and fimbria/fornix, and cerebellar white matter. At P1, MARCKS was strongly expressed in the majority of brain regions except the brainstem, which subsequently declined gradually to approximate adult levels by P14. Between P14 and P21, MARCKS expression declined gradually in the hilus, remained elevated in hippocampal CA1, CA3, and granule cell layers, and increased dramatically in the corpus callosum and fimbria/fornix. At P90, MARCKS expression declined in hippocampal CA3 and hilus and remained strongly expressed in hippocampal CA1 and granule cell layers, regions of the olfactory bulb, the medial habenula, temporal cortex, and cerebellar granule and Purkinje cells. Expression of both MARCKS and MRP in regions undergoing neuronal proliferation, migration, and neurite outgrowth suggest a common role in these developmental events, whereas differences in expression during development and in the adult brain provide evidence of differential regulation.
 ...
PMID:Distribution of the protein kinase C substrates MARCKS and MRP in the postnatal developing rat brain. 967 61


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