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)

We previously reported that protein kinase C (PKC) stimulation through phorbol ester (TPA) treatment enhances the effects of all-trans retinoic acid (RA) on immunophenotypic differentiation and RA nuclear receptor (RAR) activation in the multipotential human teratocarcinoma (TC) cell line NTera-2/clone D1 (abbreviated NT2/D1). This study extends prior work in NT2/D1 cells by demonstrating that PKC pathway activation is an early effect of RA treatment which regulates RAR transcriptional activity. RA activated the PKC pathway prior to induction of RAR-beta expression at 6 h, which is an established early marker of RAR activation in NT2/D1 cells. RA caused a transient 1.3-fold increase in intracellular diacylglycerol (DG) at 2 min and a translocation of the gamma isozyme of PKC (PKC-gamma) within 5 min. Transient co-transfection studies provided evidence that PKC pathway activation plays a role in the regulation of RAR-beta expression. In these studies a constitutively active PKC-gamma augmented the RA-mediated transactivation of a luciferase reporter containing the native RAR-beta promoter which has a retinoic-acid-response element (RARE). These findings reveal that PKC pathway activation is an early step in RA-mediated human TC differentiation and that PKC-gamma can potentiate the effects of RA on RAR transcriptional activation.
 ...
PMID:Retinoic acid stimulates the protein kinase C pathway before activation of its beta-nuclear receptor during human teratocarcinoma differentiation. 821 62

A possible regulatory function of protein kinase C (PKC) isoenzymes in zymosan-stimulated eicosanoid synthesis was studied in mouse peritoneal macrophages in culture. The addition of zymosan to intact cells labelled with [3H]arachidonic acid stimulated a time-dependent and concentration-dependent release of the fatty acid. There was a simultaneous marked increase in the synthesis of prostaglandin E2 and leukotriene C4. The protein-kinase inhibitor K-252a and the selective PKC inhibitor CGP41251 completely blocked zymosan-triggered arachidonic acid release as well as prostaglandin E2 and leukotriene C4 synthesis. In contrast, an inactive staurosporine derivative, CGP42700, failed to inhibit any of the zymosan-induced responses. The down-regulation of PKC by long-term treatment with phorbol 12-myristate 13-acetate eliminated zymosan-stimulated arachidonic acid release and eicosanoid synthesis (after 4-6 h treatment). By using specific antibodies it was observed that mouse macrophages express five PKC isoenzymes, PKC-alpha, -beta, -delta, -epsilon and -zeta. No PKC-gamma isoenzyme was detected. After exposure to phorbol 12-myristate 13-acetate, a complete depletion of PKC-beta was observed within 1 h and the complete depletion of PKC-alpha and PKC-delta isotypes was observed within 4 h. In contrast, PKC-epsilon was only partially down-regulated after a 24-h treatment with phorbol 12-myristate 13-acetate and PKC-zeta was not affected at all. These data indicate that PKC-alpha and PKC-delta isoenzymes are candidates for regulating prostaglandin and leukotriene production. From the potent inhibitory activities of K-252a and CGP41251, two compounds that reportedly display a higher selectivity for PKC-alpha compared to PKC-delta, it is suggested that PKC-alpha triggers arachidonic acid mobilization and eicosanoid synthesis in peritoneal macrophages.
 ...
PMID:A role for protein kinase C-alpha in zymosan-stimulated eicosanoid synthesis in mouse peritoneal macrophages. 822 88

Kindling is an animal model for epilepsy in which repeated application of an electrical stimulus to brain pathways results in an epileptic focus. The animal holds a permanent state of hyperexcitability to the stimulus for the rest of its life. Understanding the cellular and molecular processes underlying hyperexcitability could provide insight into epileptogenesis. Furthermore, it could elucidate cellular and molecular bases of synaptic plasticity in the central nervous system. In the present study the long-term effect of a kindled focus in the amygdala on the gamma-isoform of protein kinase C and the muscarinic cholinergic receptor as cellular messengers was evaluated in the cerebral cortex of rats. Following an average of 10 bilaterally generalized seizures kindling stimulation was terminated and rats were left undisturbed for approximately three months. Brains were processed by immunocytochemistry using monoclonal antibodies against protein kinase C-gamma and muscarinic cholinergic receptor protein. Digital image analysis of sections through the entire forebrain revealed an increase in optical density of both protein kinase C-gamma and the muscarinic cholinergic receptor in the piriform and entorhinal cortex of the hemisphere contralateral to the stimulation site in kindled rats. However, on the ipsilateral side no change was observed in comparison with electrode implanted nonkindled control rats. The observed increase in expression of muscarinic cholinergic receptor protein and a component of the phosphoinositide second messenger system (protein kinase C-gamma) located in specific areas of the cerebral cortex in kindled rats could serve as a basis for the permanent state of hyperexcitability in these rats.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Long-term increase in protein kinase C-gamma and muscarinic acetylcholine receptor expression in the cerebral cortex of amygdala-kindled rats--a quantitative immunocytochemical study. 823 6

Differential changes in the expression of PKC isoenzymes in the RA-induced differentiation were noted. As measured by Western blot analysis, our results indicated the expressions of PKC-alpha, and -beta isoenzymes decreased in the cell membrane but increased in the cytosol during the RA-induced granulocytic differentiation. The amounts of PKC-gamma, on the other hand, decreased in the cell membrane while there was no significant changes in the cytosol. Similarly, the expression of PKC-delta was not altered in the cytosol, but was slightly reduced during the SP enhancement of RA-induced differentiation. In contrast, there were virtually little changes in the expression of PKC-epsilon and -zeta in the cell membrane or in the cytosol during the RA-induced differentiation in the absence or presence of SP. Concomitant with the decreased total PKC activity, there was a decline in the generation of sn-1,2-diacylglycerol (DAG) during the RA-induced differentiation. SP, enhancing the RA-induced differentiation, also potentiated the decrease of DAG content.
 ...
PMID:Differential regulation of protein kinase C isoenzymes during sphinganine potentiation of retinoic acid-induced granulocytic differentiation in human leukemia HL-60 cells. 825 Aug 95

Using isozyme-specific anti-peptide antisera against peptides from the alpha-, beta-, gamma-, delta-, epsilon-, and zeta-isoforms of brain protein kinase C (PKC), we have identified proteins in bovine lens epithelial cells, in culture, that were reactive with these antisera. Western blots of lens epithelial cell homogenates showed that PKC-alpha antisera reacted with a major protein, and PKC-gamma antisera reacted with a minor protein. When the lens epithelial cells were cultured in media supplemented with 40 mM galactose, to model the conditions of sugar cataracts, a decrease in PKC-gamma, but not in PKC-alpha was observed. These were normalized if the cells were cultured in 40 mM galactose media supplemented with an inhibitor of aldose reductase, Tolrestat (10 microM). These results suggest that changes in PKC isoforms occur in the galactosemic diabetic state.
 ...
PMID:Protein kinase C in galactosemic and tolrestat-treated lens epithelial cells. 831 96

The effects of hypoxia on protein kinase C (PKC) isozymes (alpha, beta I, beta II, and gamma) were examined in the hippocampus from rats subjected to hypoxic conditions (5% O2 in 95% N2) for 30 min in a chamber. Western blot analysis revealed that the total amounts of PKC-alpha (-26.0% of control) and -gamma (-32.7% of control) were decreased significantly at the end of hypoxia, which was followed by the reduction of that of PKC-beta II (-23.7% of control at 7 days after hypoxia). Whereas, the PKC activities, which were measured by the incorporation of [gamma-32P] into a specific PKC substrate peptide, in both the cytosolic and the particulate fractions did not change. The reductions of PKC-gamma and -alpha at the end of hypoxia may be related to the following neuronal degeneration.
 ...
PMID:Changes in protein kinase C isozymes in the rat hippocampus following transient hypoxia. 836 41

The regulatory enzyme, protein kinase C (PKC), is characterized by a family of related isozymes. Currently, nucleotide (nt) sequences for seven members of this family have been reported from the bovine, human and rat genomes. Only four of these seven PKC isoforms have been isolated in mouse: alpha, beta II, delta and epsilon. Here, we report the cDNA sequence encoding mouse PKC-gamma isolated from a C57BL/6 brain cDNA library. The mouse and rat PKC-gamma nt and deduced amino acid sequences share 97 and 100% identity, respectively.
 ...
PMID:Isolation and sequence of a mouse brain cDNA coding for protein kinase C-gamma isozyme. 842 69

Monoclonal antibodies to the three isozymes of protein kinase C (PKC) (alpha, beta, and gamma) were applied to postmortem human retina. Immunostaining was done on wholemount, or cryostat-sectioned retina, and visualized after ABC/DAB procedures by light (LM) and electron (EM) microscopy. The PCK-alpha antibody stained rod bipolar cells throughout the retina. EM analysis confirmed they were PKC-alpha-immunoreactive (IR) on their characteristic dendritic and axonal synaptology. Putative blue cone bipolar cells with wide-field axon terminals, stratifying in s5 of the inner plexiform layer (IPL), were also PKC-alpha-IR, and EM showed them to engage in narrow-cleft ribbon junctions in blue cone pedicles. The PKC-beta antibody stained cone bipolar cells, many amacrine cells, and most ganglion cells. Cone bipolar cells were stained all the way into the foveal center: both midget and diffuse varieties were included. The IPL was densely PKC-IR and individual neurons could not be identified on stratification patterns. EM of the outer plexiform layer (OPL) revealed that both flat and invaginating cone bipolar types were IR and that IR axon terminals were presynaptic in all strata of the IPL. The occurrence of PKC-beta-IR bipolar axons in stratum 2 of the IPL suggests that OFF-center as well as ON-center types were included. The PKC-gamma antibody gave inferior staining compared with results from the other two antibodies; however, two varieties of wide-field monostratified amacrine cell and a large-bodied ganglion cell type were discernible. PKC in one form or another appears to be a second messenger used in neurotransmission by both rod and cone systems and ON- and OFF-center systems in the human retina.
 ...
PMID:Differential staining of neurons in the human retina with antibodies to protein kinase C isozymes. 848 96

Deaths from colon cancer number over 60,000 each year in the United States. Because early detection results in a high cure rate, development of noninvasive techniques for detection of colon cancer has received much interest. The ability to detect early changes in colonocyte genes and gene expression would provide valuable information. We have shown previously that alterations in protein kinase C (PKC) isoform expression are associated with changes in colonic cell proliferation, a key intermediate marker for the prediction of tumorigenesis. Here, we describe a method for the quantitative detection of mRNAs for select PKC isoforms isolated from rat feces containing exfoliated colonocytes. After total RNA extraction from fresh fecal material, polyadenylated RNA was selectively purified and quantitated with slot blotting and hybridization to oligodeoxythymidylic acid. Fecal polyadenylated RNA was used for semiquantitative (mimic) RT-PCR to quantitate PKC isoform mRNA expression. We detected mRNA for PKC-alpha, PKC-delta, PKC-epsilon, and PKC-sigma, but not for PKC-beta or PKC-gamma, which is consistent with the profile of isoforms detected previously in scraped colonic mucosa using immunoblot analysis. This noninvasive method, utilizing feces containing exfoliated colonocytes, is a sensitive noninvasive technique for quantitating luminal mRNAs. This provides a means to monitor gene expression of colonic epithelial cells, which may have predictive value in monitoring the neoplastic process.
 ...
PMID:Noninvasive detection of putative biomarkers for colon cancer using fecal messenger RNA. 854 31

This study describes changes in the immunoreactivity for muscarinic acetylcholine receptors (mAChRs) in the hippocampus of mice in relation to spatial discrimination behavior, employing the monoclonal antibody M35 raised against purified bovine mAChR protein. Performance in a hole board in which the animals learned the pattern of 4 baited holes out of 16 holes served as the measure of spatial discrimination learning and memory. Twenty-six adult male house mice were used, divided into four groups. Three groups served as various controls: group N (naive; blank controls); group H (habituated; animals were introduced to the hole board with all holes baited for 5 consecutive days), and group P (pseudo-trained; the animals were admitted to the hole board for 13 consecutive days with all holes baited). The T group (trained) was subjected to the hole board for 5 consecutive habituation days with all holes baited (similar to the H and P groups), followed by 8 successive training days with only four holes baited in a fixed pattern. During the 8 training days, the T group gradually acquired a pattern to visit the baited holes, whereas the P group continued visiting holes in a random fashion. The mice were killed 24 h after the last behavioral session. All principal cells in teh cornu ammonis (CA) and dentate gyrus (DG) of the habituated animals revealed increased levels of mAChR immunoreactivity (mAChR-ir) over the naive mice. A minor increase in mAChR-ir was found in the apical dendrites of the CA1 pyramidal cells. Pseudotraining resulted in a CA1-CA2 region with a low level of mAChR-ir, resembling naive animals, whereas the trained mice showed a further increase in mAChR-ir in the CA1-CA2 pyramidal cell bodies and apical dendrites. Optical density measures of the mAChR-ir in the CA1 region revealed a significant (P < 0.05) increase in the pyramidal cell bodies of the H and T group over the N and P group, and a significant (P < 0.05) increase in the apical dendrites of the T group over all other groups. In contrast to the CA1-CA2 region, both pseudotrained and trained mice revealed high mAChR staining in the CA3-CA4 region and the DG. These results indicate that prolonged exposure to the hole board is sufficient for an enhanced mAChR-ir in the CA3-CA4 and DG, whereas the increase in CA1-CA2 pyramidal cells is a training-specific feature related to spatial orientation. Nonpyramidal neurons within the CA1-CA2 region with enhanced mAChR-ir in the pyramidal cells, however, revealed a decreased level of mAChR-ir. The opposing effect of pyramidal and nonpyramidal cells suggests a shift in the excitability of the hippocampal microcircuitry. Previously we demonstrated an increase and redistribution of hippocampal protein kinase C gamma-immunoreactivity (PKC gamma-ir) induced by hole board learning in mice (Van der Zee et al., 1992, J Neurosci 12:4808-4815). Immunofluorescence double-labeling experiments conducted in the present study in naive and trained animals revealed that the principal cells and DG interneurons co-express mAChRs and PKC gamma, and that the immunoreactivity for both markers increased in relation to spatial orientation within these neurons. The mAChR-positive nonpyramidal cells of the CA1-CA2 region were devoid of PKC gamma and revealed an opposite training-induced effect. These results suggest that the postsynaptic changes in mAChR- and PKC gamma-ir reflect functional alterations of the hippocampal formation induced by spatial learning.
 ...
PMID:Alterations in the immunoreactivity for muscarinic acetylcholine receptors and colocalized PKC gamma in mouse hippocampus induced by spatial discrimination learning. 858 98


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