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

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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)

Total PKC activity in BAEC incubated for 24 hrs in either 10% serum (FBS) or serum-deprived media (SDM) was similar. However, most of the activity (69%) in the FBS group was detected in the particulate fraction, while it was mainly in the cytosolic fraction (66%) in the SDM group. By confocal microscopy, there was diffuse cytoplasmic localization of the antibodies to the alpha and beta PKC isoforms. gamma PKC was not detected. Treatment of FBS or SDM cells with a phorbol ester resulted in an increase in PKC activity with translocation to the particulate fraction. PKC alpha immunofluorescence redistributed to the perinuclear region whereas PKC beta staining remained mostly cytosolic. Calphostin C, a PKC inhibitor, prevented the phorbol ester-induced increase in PKC activity and translocation.
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PMID:Immunocytochemical expression and localization of protein kinase C in bovine aortic endothelial cells. 144 92

The respiratory burst of phagocytes in an important leukocyte function which results in generation of oxygen species that are both microbicidal and potentially damaging to host tissues. We investigated regulation of the respiratory burst of alveolar macrophages in response to lipopolysaccharide (LPS) derived from gram-negative bacteria, serum proteins, and several modulators of signal transduction. When employed as a single stimulus, LPS (E. coli 055:B5, 10 ng/ml-1 microgram/ml) was a weak stimulus for generation of superoxide anion (O2-) as compared to the potent effect of the protein kinase C activator, phorbol 12-myristate 13-acetate (PMA; 500 ng/ml). However, when LPS was combined with fetal bovine serum (FBS; 0.4-1.0% vol/vol, equivalent to 128-320 micrograms protein/ml), O2- generation was enhanced approximately two-fold over LPS alone. A chromatographically-derived bovine serum fraction which contained bovine lipopolysaccharide-binding protein (bLBP; 0.25-1.0 microgram/ml) was an effective substitute for FBS at a much lower protein concentration than whole FBS, and a similar synergistic effect with LPS on O2- generation was observed. Stimulation of macrophages for generation of O2- either with LPS alone or with LPS plus serum/serum fraction was suppressed by the protein tyrosine kinase inhibitor heribimycin A (0.2 ng/ml), and the calcium chelator BAPTA (12 microM), but not by modulators of G-proteins, including pertussis toxin (10 ng/ml) and cholera toxin (5 micrograms/ml protein). Essentially complete inhibition of O2- synthesis by herbimycin A and BAPTA occurred in the presence of LPS and the bLBP-containing serum fraction (1 microgram/ml protein), but only partial inhibition (46.7% and 64.1%, respectively) was observed in the presence of LPS plus FBS (256 micrograms/ml protein). These results indicate that when LPS is used as a sole stimulus it induces modest respiratory burst activity. However, when LPS is combined with appropriate serum components, it stimulates alveolar macrophages to generate larger amounts of O2-. Cellular signaling pathways important in stimulation of macrophages by LPS and serum components are protein tyrosine kinase- and Ca(++)-dependent, but do not relay on G-protein-mediated signaling.
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PMID:Regulation of superoxide anion generation in bovine alveolar macrophages by bacterial lipopolysaccharide, serum proteins, and modulators of signal transduction. 859 31

As an initial step in testing the hypothesis that high oleic acid concentrations contribute to vascular remodeling in obese hypertensive patients by activating protein kinase C (PKC), the effects of oleic acid on primary cultures of rat aortic smooth muscle cells (RASMCs) were studied. Oleic acid, an 18-carbon cis-monounsaturated fatty acid (18:1 [cis]), from 25 to 200 mumol/L significantly increased [3H]thymidine uptake in RASMCs with an EC50 of 41.0 mumol/L and a maximal response of 196 +/- 15% of control (P < .01). Oleic acid from 25 to 200 mumol/L caused a concentration-dependent increase in the number of RASMCs in culture at 6 days, reaching a maximum of 210 +/- 13% of control at 100 mumol/L (P < .001). PKC inhibition with 4 mumol/L bisindolyImaleimide I and PKC depletion (alpha, mu, iota, and zeta) with 24-hour exposure to 200 nmol/L phorbol 12-myristate 13-acetate in RASMCs eliminated the mitogenic effects of oleic acid but did not reduce responses to 10% FBS. Stimulation of intact cells with oleic acid induced a peak increase of cytosolic PKC activity, reaching 328 +/- 8% of control (P < .001), but did not enhance PKC activity in the membrane fraction (105 +/- 4%, P = NS). The oleic acid-induced increase of PKC activity in cell lysates was similar in the presence and absence of Ca2+, phosphatidylserine, and diolein (maximum response, 360 +/- 4% versus 342 +/- 9% of control, P = NS). Unlike phorbol 12-myristate 13-acetate, oleic acid over 24 hours did not downregulate any of the four PKC isoforms detected in RASMCs. Oleic acid treatment activated mitogen-activated protein (MAP) kinase. PKC depletion in RASMCs eliminated the rise in thymidine uptake, activation of PKC, and activation of MAP kinase in response to oleic acid. In contrast to oleic acid, 50 to 200 mumol/L stearic (18:0) and elaidic (18:1 [trans]) acids, which are less effective activators of PKC than oleic acid, did not enhance thymidine uptake. These data suggest that oleic acid induces proliferation of RASMCs by activating PKC, particularly one or more of the Ca(2+)-independent isoforms, and raise the possibility that the higher oleic acid concentrations observed in obese hypertensive patients may contribute to vascular remodeling.
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PMID:Oleic acid-induced mitogenic signaling in vascular smooth muscle cells. A role for protein kinase C. 878 94

To determine what factors regulate gonocyte proliferation in newborn rats, we first examined the expression of several signal transduction molecules by immunocytochemistry in 3-day-old rat testis sections. We found that gonocytes specifically expressed the iota and zeta isoforms of protein kinase (PK) C (PKC) and the phosphatidylinositol 3-kinase (PI3-K). Because both the zeta PKC and PI 3-K have been shown to play a role in platelet-derived growth factor (PDGF)-induced cell proliferation, we examined the effects of PDGF on gonocytes. For this, we developed a method to obtain highly purified and viable gonocytes in culture. After enzymatic digestion, differential adhesion, and two successive gradient fractionations, the gonocyte suspension obtained was over 90% pure, as assessed by light microscopy. The viability of cultured gonocytes exceeded 90% after 48 h in the presence of 2.5% FBS used as a survival factor. Immunodetection studies showed that isolated gonocytes expressed zeta PKC, PI 3-K, and the PDGF receptor. Treatment with 10 ng/ml PDGF induced a 4-fold increase of bromodeoxyuridine incorporation into gonocytes (from 5% proliferative gonocytes under basal conditions to 20% in the presence of PDGF). Because neonatal Sertoli cells secrete high levels of the growth promoting steroid, 17 beta-estradiol, we also tested its effect and found that it induced gonocyte proliferation at a level comparable with that of PDGF and that this effect was blocked by the estrogen receptor antagonist, ICI 164384. The combination of PDGF and estradiol, however, was not additive, suggesting that their effects were mediated by common molecular target(s). These results demonstrate that PDGF and estradiol activate gonocyte proliferation in vitro, suggesting that they may act as the physiological regulators of gonocyte development in vivo.
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PMID:Regulation of rat testis gonocyte proliferation by platelet-derived growth factor and estradiol: identification of signaling mechanisms involved. 904 38

Recent studies indicate that vitamin D metabolites exert rapid effects on growth plate chondrocytes via changes in PG production and protein kinase C (PKC) activity. This suggests that these two products of vitamin D action may be interrelated. To test this hypothesis, we examined the effect of PGE2 on rat costochondral resting zone and growth zone cartilage cells and determined whether the effects of PGE2 are mediated by changes in the level of cAMP and/or PKC activity, whether there is a relationship between cAMP production and PKC activity, and whether cell maturation-specific effects are involved. Confluent, fourth passage resting zone and growth zone cartilage cell cultures were incubated in DMEM containing 10% FBS, 50 microg/ml vitamin C, and 1% antibiotics. The PGE2 concentration was varied from 0.007-15 ng/ml. Low concentrations of PGE2 caused a dose-dependent increase in cell number and [3H]thymidine incorporation and stimulated alkaline phosphatase specific activity. These effects were comparable in resting zone and growth zone cartilage cells at the same PGE2 concentrations. At higher concentrations, PGE2 caused a general increase in the synthesis of collagenase-digestible protein and noncollagenase-digestible protein in resting zone cartilage cells and of collagenase-digestible protein in growth zone cartilage cells, resulting in a net increase in the percent collagen synthesis for both cell types. cAMP production was increased over the entire range of chondrocyte response. Prevention of cAMP metabolism with the protein kinase A inhibitors H-8 and H-89 blocked the PGE2-dependent inhibition of PKC in resting zone cartilage cells in a dose-dependent manner. H-8 alone had no effect on PKC in resting zone cartilage cells, but stimulated PKC activity in growth zone cartilage cells; H-89 alone stimulated PKC activity in resting zone cartilage cells. These results suggest that low levels of PGE2 promote differentiation, whereas high doses promote an anabolic response; PGE2 increases cAMP production and PKC activity in a cell maturation-dependent manner; PGE2 exerts its effects via cAMP production and PKC activity; and regulation of PGE2-dependent PKC is via cAMP.
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PMID:The effect of prostaglandin E2 on costochondral chondrocyte differentiation is mediated by cyclic adenosine 3',5'-monophosphate and protein kinase C. 952 68

Oxytocin (OT) receptors (OTRs) have been demonstrated in a number of human breast tumors and tumor cells, but it was not clear whether the receptors were functional. We examined the regulation and function of OTR in a tumor cell line, Hs578T, derived from human breast. These cells expressed moderate levels of OTR when cultured in 10% FBS, as demonstrated by RT-PCR and binding analyses. Serum deprivation resulted in the loss of OTRs, with no effect on cell viability. Restoration of serum and addition of 1 microM dexamethasone (DEX) increased OTR levels by about 9-fold. Up-regulation was blocked by the addition of phospholipase C and PKC inhibitors. Serum/DEX treatment also increased steady state OTR messenger RNA levels. OT increased intracellular Ca2+ in a time- and dose-responsive manner, and the effects of OT were lost when OTRs were down-regulated by serum starvation. Serum/DEX up-regulation of OTR restored the responsiveness to OT. OT also stimulated ERK-2 (extracellular signal-regulated protein kinase) phosphorylation and PGE2 synthesis in Hs578T cells. In addition to showing that OTRs in the breast tumor cells are functional, these studies show that Hs578T cells can be used to study molecular regulation of OTR gene expression and intracellular signaling pathways stimulated by OT.
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PMID:Demonstration of functional oxytocin receptors in human breast Hs578T cells and their up-regulation through a protein kinase C-dependent pathway. 1021 79

Rat osteoblasts were isolated from the 21-day fetal rat calvarias. The cells were grown in DMEM plus 10% FBS, and were treated for 24 h. with 10 mumol/L TPEN or 10 mumol/L TPEN supplemented with 10 mumol/L Zn2+. Apoptosis of osteoblasts were measured by flow cytometry, electron microscopy and DNA fragmentation analyzed by gel electrophoresis. In addition, IP3 production and PKC activity were measured in order to show whether they are involved in apoptosis in osteoblast induced by zinc deficiency. The results showed that 10 mumol/L TPEN could induce apoptosis in osteoblast in 24 h. But cells treated with 10 mumol/L TPEN supplemented with 10 mumol/L Zn2+ showed no apoptotic changes in 24 h. TPEN significantly reduced the formation of IP3 and PKC activity after 24 h incubation. No differences were observed between the cells treated with TPEN supplemented with Zn2+ simultaneously and the untreated cells. It can be inferred that apoptosis induced by zinc deficiency may be due to the decreased activity of PKC which is impaired by reduced formation of IP3.
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PMID:Apoptosis induced by zinc deficiency in rat osteoblast: possible involvement of protein kinase C. 1067 79

The role of endogenous regucalcin, which is a regulatory protein in calcium signaling, in the regulation of protein kinase activity in the proliferation of the cloned rat hepatoma cells (H4-II-E) was investigated. Hepatoma cells were cultured for 6-72 h in the presence of fetal bovine serum (FBS; 1 or 10%). The number of cells and protein kinase activity in the 5500 g supernatant of cell homogenate was significantly increased 24 and 48 h after the culture with FBS (1 or 10%); the culture with 10% FBS was potent effect as compared with that of 1% FBS. FBS (10%)-increased protein kinase activity preceded a significant elevation of cell number of 6 h after culture. Serum stimulation-induced increase in protein kinase activity was significantly decreased in the presence of trifluoperazine (50 microM), staurosporine (10(-6) M) or genistein (10(-5) M) in the enzyme reaction mixture. The presence of anti-regucalcin monoclonal antibody (40 or 80 ng/ml) in the reaction mixture caused a significant increase in protein kinase activity in the cells cultured with FBS (1 or 10%). This increase was completely blocked by addition of regucalcin (10(-6) M), which can reveal an inhibitory effect on protein kinase activity. Moreover, the effect of antibody in increasing protein kinase activity was significantly inhibited in the presence of trifluoperazine, staurosporine, or genistein, indicating that endogenous regucalcin has an inhibitory effect on Ca(2+)/calmodulin-dependent protein kinase, protein kinase C, and protein tyrosine kinase. The present study suggests that endogenous regucalcin plays a suppressive role in the enhancement of various protein kinase activities associated with a proliferation of the cloned rat hepatoma cells (H4-II-E).
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PMID:Suppressive role of endogenous regucalcin in the enhancement of protein kinase activity with proliferation of cloned rat hepatoma cells (H4-II-E). 1145 66

Proliferation of vascular smooth muscle cells stimulated by reactive oxygen species (ROS) may play a pivotal role in the pathogenesis of atherosclerosis. To clarify mechanisms by which ROS promote vascular atherogenesis, effects of fluvastatin, amlodipine, ozagrel (thromboxane synthetase inhibitor), GF109203X (a protein kinase C inhibitor) and Y27632 (a ROCK inhibitor) on the proliferation of guinea-pig basilar artery smooth muscle cells (GBa-SM3) in a 5% FBS culture medium were studied over 3 d in the presence or absence of a free radical scavenger, edaravone. Viability of cells at the end of incubation was measured by the 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) test. Results demonstrated that fluvastatin and amlodipine by themselves possess antiproliferative effects on the GBa-SM3 cells at 10-100 microM and 0.1-1 microM, respectively. While edaravone possessed no antiproliferative effect by itself at 100 microM, it significantly (p<0.05) augmented the antiproliferative effects of fluvastatin and amlodipine. In addition, ozagrel, GF109203X and Y27632 possessed no appreciable effects on the cell growth by themselves. However, coincubation of edaravone at 100 microM with these agents elicited significant antiproliferative effects for ozagrel, GF109203X and Y27632 at 10-100 microM, 1-10 microM and 0.1-1 microM, respectively. In conclusion, edaravone may have clinically beneficial interactions with fluvastatin, amlodipine and ozagrel regarding the prevention of vascular atherosclerosis. The interactions between edaravone and the inhibitors of protein kinase C and ROCK were suggestive of possible contributions of ROS-triggered intracellular signals associated with these enzymes to vascular atherogenesis, but further studies are required for confirmation.
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PMID:Edaravone, a radical scavenger, may enhance or produce antiproliferative effects of fluvastatin, amlodipine, ozagrel, GF109203X and Y27632 on cultured basilar artery smooth muscle cells. 1464 75

The role of protein kinase C (PKC) in the regulation of contraction has been controversial. Recently, CPI-17, a PKC-potentiated inhibitor protein of PP1, has been cloned and shown to be specifically expressed in SMC. In this study, we over-expressed CPI-17 and its mutants in NIH3T3 cells, which do not express CPI-17, and examined its effect on the contractile property. For the measurement of tension, NIH3T3 cells were collected by trypsinization, mixed with type I collagen and made into a ring preparation (reconstituted ring: RR). The isometric tension developments were measured using this RR and a force transducer. The application of phorbol dibutyrate (PDBu; 0.3 microM) to RR transfected by CPI-17 induced a contraction that reached 2-3 times greater that the 10% FBS-induced contraction, while PDBu relaxed the RR transfected with vector alone (control) or CPI-17 mutants (T38A and T38E). The PDBu-induced contraction of the CPI-17 transfected RR could be inhibited by 3 microM GF109203X (PKC inhibitor) but not by 3 microM Y27632 (rho kinase inhibitor). The application of PDBu during contraction induced by 1 microM bradykinin induced further contraction in CPI-17 transfected RR, while it induced a complete relaxation in control RR. These results indicated that CPI-17 is a molecular switch that reverses the PKC mediated effect on contraction. The limited expression of CPI-17 to SMC may explain the previous observation that the effects of PKC stimulation were quite different in SMC from those of other cell types.
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PMID:[Changes in the contractility of the NIH3T3 fibroblast induced by the over-expression of CPI-17]. 1472 19


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