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)

A slow freeze/fast thaw tissue preparation gave analogous hippocampal protein kinase C (PKC) activity to a fresh tissue preparation in both C57BL/6 and DBA/2 mice. Both the frozen and fresh preparations demonstrated a 28% reduction in membrane-bound PKC activity in DBA compared to C57 mice which supports our previous findings (14). This DBA-associated reduction was found only in total PKC and not synaptosomal PKC activity suggesting that the PKC difference between C57 and DBA mice may be primarily postsynaptic. This investigation shows that (1) PKC activity obtained from a slow freeze/fast thaw preparation is analogous to activity obtained from fresh tissue and (2) analysis of PKC activity in both a total and synaptosomal preparation may provide additional characterization of PKC differences such as that observed between C57 and DBA mice.
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PMID:Determination of hippocampal protein kinase C using a frozen tissue method: comparison of synaptosomal and total activity in C57BL/6 and DBA/2 mice. 144 14

Previous work from our laboratory demonstrated that 12-O-tetradecanoylphorbol-13-acetate (TPA) or a synthetic diacylglycerol induced significantly higher epidermal ornithine decarboxylase (ODC) activity in C57BL/6 than in DBA/2 mice. To understand further the genetic basis for this strain difference, two tumor promoters were evaluated for their effects on epidermal ODC activity: teleocidin, which activates protein kinase C (PKC); and 1,8-dihydroxyl-3-methyl-9-anthrone (chrysarobin), which does not. In addition, the ODC induction response in B6D2F1 offspring and BXD recombinant inbred (RI) strains was examined following multiple treatments with TPA. A single topical application of teleocidin to mouse dorsal skin led to the hyperinduction of epidermal ODC activity in C57BL/6 mice. In contrast, while chrysarobin induced epidermal ODC activity, no significant differences in the magnitude of this response were observed in SENCAR, DBA/2 or C57BL/6 mice. Consistent with our previous findings, the magnitude of ODC induction by teleocidin in these three mouse lines (C57BL/6 greater than SENCAR greater than DBA/2) did not correlate with their susceptibility to tumor promotion by TPA (SENCAR greater than DBA/2 greater than C57BL/6). ODC activity induced by multiple application of TPA in B6DF1 mice, whose susceptibility to phorbol ester tumor promotion is inherited as an incomplete dominant trait, was comparable to that induced in C57BL/6 mice at all the doses examined. Cluster analysis of TPA-induced ODC activity in BXD RI strains allowed us tentatively to group them into four or five phenotypes and to estimate a minimum of two genetic loci controlling TPA-induced ODC activity. Furthermore, in BXD RI strains, there was no apparent relationship between the magnitude of ODC induction and responsiveness to tumor promotion or sustained hyperplasia. Collectively, these results suggest that hyperinducibility of ODC in response to PKC-activating tumor promoters is inherited as an autosomal dominant trait, and that genetic determinants for ODC induction, at least in C57BL/6 and DBA/2 mice, appear completely independent of those controlling tumor promotion susceptibility.
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PMID:Enhanced induction of epidermal ornithine decarboxylase activity in C57BL/6 compared to DBA/2 mice by protein kinase C-activating skin tumor promoters: relevance to genetically mediated differences in promotion susceptibility. 174 6

The role of second messengers in the response of alloactivated T cells to growth factors (e.g., interleukin-2) is unknown. We have previously found that intracellular calcium may be an important T-cell alloactivation marker. To determine whether protein kinase C (PKC) is also involved in allosensitized T cell function, we studied the effects of the PKC agonists phorbol 12-myristate 13-acetate (PMA), mezerein (MEZ), and 1-oleoyl-2-acetylglycerol (OAG) and the PKC antagonists phloretin and D-sphingosine on the in vitro proliferation and migration of allosensitized cells from a C57BL/6 anti-DBA/2J mixed leukocyte culture (MLC). At 0.01-1.0 microgram/ml, PMA, a potent stimulant of PKC, exerted profound stimulatory effects on secondary MLC supernatant (2 degrees SN)-induced proliferation of allosensitized T cells (132-200% increase, P less than 0.01). Both MEZ and OAG are less potent activators of PKC than PMA but also stimulated T cell proliferation (132-152% of control, P less than 0.01). The PKC antagonists phloretin and D-sphingosine both inhibited proliferation by greater than 50% at 1.0-10.0 microM (P less than 0.01). Further experiments showed that these agents exert similar effects on in vitro T cell locomotion in a Boyden chamber assay. These data indicate that PKC activation may be an important component of allosensitized T cell proliferation and locomotion and may constitute a pathway by which T cell function may be modified in the allograft response.
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PMID:Evidence that protein kinase C regulates allosensitized T lymphocyte function. 205 67

The present study has characterized several aspects of the mouse epidermal protein kinase C (PKC) system and compared phorbol ester-sensitive and -resistant mice. Protein immunoblots of partially purified epidermal PKC preparations from SENCAR and C57BL/6 mice indicated the presence of the gamma-, beta-, and alpha-isozymes of PKC in both strains. Hydroxylapatite chromatography profiles of epidermal PKC isozymes from SENCAR and C57BL/6 mice revealed three major peaks of PKC activity eluting in fractions similar to those observed in chromatograms of brain tissue and corresponding to PKC-gamma, -beta, and -alpha. Further analyses of hydroxylapatite chromatography fractions revealed that PKC-gamma and -beta were present in approximately similar proportions and were much more abundant than PKC-alpha. This distribution of epidermal PKC isozymes was similar in both strains. After a single topical application of 3.4 nmol 12-O-tetradecanoylphorbol-13-acetate (TPA) to SENCAR mouse epidermis, total PKC activity in the cytosol fraction decreased rapidly to about 50% of control within 15 min and was accompanied by an increase (approximately 150% of control) of PKC activity in the membrane fraction. At 4 h, PKC activities were significantly lower than the control levels and remained downregulated through 96 h with a maximal decrease (to approximately 25-30% of the control) in both cytosol and membrane fractions at h. PKC activity returned to control levels by 168 h. Ca++/phospholipid-independent kinase activity was the same as control levels at 15 min, 1 h, and 4 h after TPA treatment but was elevated above control levels at 24 h, 48 h, and 96 h, and by 168 h returned essentially to control levels. No differences were found in the magnitude or kinetics of TPA-induced translocation and downregulation of total PKC or appearance of Ca++/phospholipid-independent kinase activity between SENCAR, DBA/2, and C57BL/6 mice. Scatchard analyses using a two binding site model revealed that the apparent Kd and Bmax values for binding of PDBu to epidermal cytosol and membrane fractions were similar between SSln, SENCAR, DBA/2, and C57BL/6 mice. The present results demonstrate for the first time that mouse epidermis contains significant amounts of the three major PKC isozymes that are present in brain, especially PKC-gamma. In addition, topical application of a promoting dose of TPA did not lead to complete loss of PKC activity in either the membrane or cytosol fractions of mouse epidermis. In conclusion, no differences were observed between phorbol ester-sensitive and -resistant mice in any aspect of epidermal PKC examined.
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PMID:Partial characterization of epidermal protein kinase C in mice sensitive or resistant to phorbol ester. 237 71

1,2-Dioleoyl-rac-glycerol, a potent activator of protein kinase C, was found to enhance the growth-inhibitory effect of triamcinolone acetonide on L5178Y lymphoblasts in adrenalectomized, male DBA/2 mice. On the other hand, in mice without adrenalectomy, it markedly inhibited tumor growth without increasing the plasma level of corticosterone or adrenocorticotropic hormone or reducing the body weight. These results suggest that diacylglycerol enhances the action of endogenous glucocorticoid to a sufficient level to inhibit the growth of lymphoblasts. Of various diacylglycerols with different carbon chain lengths tested, 1,2-dioleoyl-rac-glycerol was the most potent growth inhibitor and was maximally effective at a dose of above 30 micrograms/100 g body weight. This finding suggests that diacylglycerols may be useful for enhancing the antitumor effect of a low dose of glucocorticoid or endogenous glucocorticoid on lymphoblasts without any significant side effect.
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PMID:Diacylglycerols enhance the anti-tumor effect of glucocorticoid on L5178Y lymphoblasts in vivo. 255 70

The purpose of this study was to examine the activity and associated kinetic parameters of epidermal protein kinase C (PKC) following stimulation by sn-1,2-dioctanoylglycerol (DIC8) or 12-O-tetradecanoylphorbol-13-acetate (TPA) and to examine the relationship between levels of epidermal PKC activity and the induction of ornithine decarboxylase by these agents, utilizing various stocks and strains of mice. Importantly, the mouse strains and stock used in this study have known differing susceptibilities to undergo TPA-induced tumor promotion: the CD-1 stock and the DBA/2 strain (both sensitive to TPA-induced tumor promotion) and the C57BL/6 strain (resistant to TPA-induced tumor promotion). TPA-stimulated protein kinase C activity was measured in the 10(5)g supernatant fraction of epidermal homogenates using lysine-rich histone as a phosphate acceptor substrate. The maximal velocities for TPA-stimulated epidermal PKC activity in CD-1, DBA/2 and C57BL/6 were 0.28, 0.29 and 0.27 nmol PO4-histone/mg 10(5)g protein/min, respectively. TPA-stimulated epidermal PKC from CD-1, DBA/2 and C57BL/6 had similar theoretical Vmax values and the apparent concentrations of TPA yielding half-maximal stimulation of PKC were also similar. DiC8-stimulated PKC activity to a greater Vmax; however, the concentration required to yield half-maximal stimulation of PKC was one thousand times greater than that of TPA. There were no strain differences in these parameters when the enzyme was stimulated with DiC8. Thus, the levels of epidermal PKC activity in CD-1, DBA/2 and C57BL/6 mice exhibit no strain differences when stimulated by TPA or DiC8 using lysine-rich histone as a phosphate acceptor substrate. Since sn-1,2-diacylglycerols are known effective inducers of epidermal ornithine decarboxylase (ODC) activity, the induction of epidermal ODC was examined in each mouse strain 5 h after topical application of 2 nmol TPA, 5 nmol TPA or 2.5 mumol DiC8. After topical treatment with TPA, C57BL/6 demonstrated an unexpected 2- and 4-fold increase in ODC activity over CD-1 and DBA/2 mice. After treatment with DiC8, C57BL/6 demonstrated a 6- and 10-fold increase in ODC activity over CD-1 and DBA/2, respectively. Thus, the resistant strain (C57BL/6) demonstrated a 'hyperinducibility' of epidermal ODC activity by TPA or DiC8. The time course for the induction of epidermal ODC was examined in each strain, and at every time point measured (3-15 h), the C57BL/6 strain exhibited this 'hyperinducibility' of ODC relative to the other strains. Epidermal DNA synthesis was stimulated to a similar extent in C57BL/6 and CD-1 mice.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Comparison of epidermal protein kinase C activity, ornithine decarboxylase induction and DNA synthesis stimulated by TPA or dioctanoylglycerol in mouse strains with differing susceptibility to TPA-induced tumor promotion. 270 40

Measures of protein kinase C (PKC) in C57BL/6 and DBA/2 mice using [3H]phorbol 12,13-dibutyrate binding to tissue homogenates and brain slices demonstrated that levels of activated, membrane-bound PKC were greater in C57BL hippocampus than in DBA hippocampus. Western analysis of alpha-, beta I-, beta II-, gamma-, delta-, and epsilon-PKC using isozyme-specific antibodies indicated that the increase observed in C57BL hippocampus was due primarily to the gamma-PKC protein, whose immunoreactivity was greater in the membrane-bound fraction in C57BL mice. Characterization of alpha-, beta I,II-, and gamma-PKC hippocampal mRNA using northern analysis and isozyme-specific nucleic acid probes did not reveal differences between the strains in levels of gene expression. Restriction fragment length polymorphisms (RFLP) were found in the alpha- and gamma-, but not beta-PKC genomic DNA. The RFLPs appeared to be located in noncoding, nonregulatory regions of the gene. These findings suggest that the gamma-PKC isozyme is largely responsible for the PKC activity difference in C57BL and DBA hippocampus that has been reported previously and may be closely associated with differences in learning ability observed in these strains.
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PMID:Protein and molecular characterization of hippocampal protein kinase C in C57BL/6 and DBA/2 mice. 776 54

We have reported that C57BL/6 and DBA/2 mice differ in spatial learning performance and associated hippocampal protein kinase C (PKC) activity (Upchurch and Wehner, 1989, Behav Neurosci 103:1251-1258; Wehner et al., 1990, Brain Res 523:181-187) and that physical activity enhances spatial learning with related alterations in protein kinase C (PKC) (Fordyce and Wehner, 1993b, Brain Res 619:111-119). To assess whether physical activity induces alterations in gene expression that may underlie these changes in PKC and learning performance, we examined the effect of physical activity on expression of zif268, a transcription regulatory factor linked to stimulus-induced neuronal plasticity. C57 and DBA mice, 3 months of age, were subjected to acute (one bout) or chronic (8 weeks) physical activity. The mice were then tested on the Morris water maze task for 6 days with subsequent analysis of PKC activity and zif268 mRNA expression. Control DBA mice, which have poor hippocampal-specific learning performance compared to C57 mice (Wehner et al., 1990, Brain Res 523-181-187; Fordyce and Wehner, 1993b, Brain Res 619:111-119; Paylor et al., 1993, Psychobiology 27:11-26), displayed lower basal levels of zif268 mRNA (P < .05). As observed previously, chronic physical activity produced an enhancement in spatial learning performance accompanied by alterations in hippocampal PKC activity in both strains of mice (P < .05). In addition, the present investigation demonstrated that acute physical activity increased mRNA levels of zif268 in hippocampal regions CA1, CA3 and overlying cortex (P < .005) of both C57 and DBA mice. Chronic physical activity suppressed the basal expression of zif268 in C57 mice in CA1 and overlying cortex below control levels. These findings suggest that genetic and activity-dependent regulation of zif268 may influence learning performance.
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PMID:Genetic and activity-dependent regulation of zif268 expression: association with spatial learning. 788 26

Bryostatin 1 (Bryo) is a potent activator of protein kinase C. When T cells are stimulated with Bryo and the calcium ionophore ionomycin (Io), they expand rapidly in low-dose IL-2 (20 U/ml). We have shown that Bryo/Io-activated T-cells from murine tumor-draining lymph nodes have striking antigen-specific antitumor efficacy in vivo. To account for the specificity despite using a nonspecific T cell activation method, it was postulated that the Bryo/Io combination might preferentially activate antigen-sensitized T cells. To test this hypothesis, an allogeneic response model was used. C57BL/6 mice were primed by intraperitoneal (ip) injection with DBA/2 mouse splenocytes. After 9 days, the C57BL/6 spleens were harvested and H-2d-specific cytolytic T lymphocyte (CTL) precursor frequency (PF) was determined by limiting dilution analysis (LDA). A portion of the same spleen cells was treated for 18 hr with Bryo/Io and expanded for 7 days in IL-2 (20 U/ml); the LDA was then repeated to analyze PF after expansion. The entire experiment was also done with responder and stimulator strains reversed (DBA/2 mice immunized with C57BL/6 cells). The resulting PF values were [table: see text] Normal spleen cells treated with Bryo/Io exhibited < 10% release vs the same targets at any effector:target ratio, ruling out nonspecific cytolysis after Bryo/Io. T lymphocytes or CD8+ T cells were selected from primed splenocytes and the PF values before and after Bryo/Io were analyzed. These data showed that the increase in PF after expansion could not be attributed to T cell or CD8+ cell enrichment alone.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Precursor frequency analysis of bryostatin activated lymphocytes. 804 Nov 53

This study determined the ontogenic changes in learning and hippocampal protein kinase C (PKC) in C57 and DBA mice. Mice were tested on the visible- or hidden-platform versions of the Morris water task starting at 17, 24, 31, or 60 days of age. Both strains learned to locate the visible platform at all ages. C57 mice learned to solve the hidden-platform task when they were 24 days old, whereas DBA mice never learned to solve this task. Using a [3H]-phorbol ester binding assay, the authors found that both strains had similar amounts of hippocampal PKC at 10 and 17 days of age but that C57 mice had significantly more PKC at 24, 31, and 60 days of age. Immunoblotting results revealed that C57 mice had more gamma-PKC, but not alpha-PKC, than DBA mice. Thus, the development of performance differences in spatial learning between C57 and DBA mice parallels the ontogeny of hippocampal PKC.
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PMID:Developmental differences in place-learning performance between C57BL/6 and DBA/2 mice parallel the ontogeny of hippocampal protein kinase C. 898 42


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