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)

The inhibitory action of azelastine hydrochloride (Azeptin) on the respiratory burst in peripheral polymorphonuclear leukocytes (PMN) and pulmonary alveolar macrophages (PAM) has been studied. Azeptin in vitro suppressed chemiluminescence and superoxide (O2-) generation by human PMN in a dose- and time-dependent manner. Phorbol myristyl acetate (PMA) and formyl-methionyl-leucyl-phenylalanine (FMLP)-induced O2- generation were strongly suppressed by 10(-6) M and 10(-5) M Azeptin, respectively. PMN and PAM from rabbits injected with Azeptin 0.2 mg.kg-1 for 5 days showed lower chemiluminescence and O2- generation than cells from untreated rabbits. Nitroblue tetrazolium reduction activity in human PMN was suppressed by treatment of PMN with 10(-6) M Azeptin for 6 h. Inositol trisphosphate, intracellular free calcium, and protein kinase C activity were decreased by 10(-6) M to 10(-5) M Azeptin. The tyrosine phosphorylation of many proteins, especially a 115 kDa protein, was suppressed by 10(-5) M Azeptin. However, superoxide dismutase activity in PMN, PAM, and lung tissue samples was only slightly decreased, even when the rabbits were treated with 1.0 mg.kg-1 Azeptin for 5 days. The results suggest that Azeptin suppresses multiple signal transduction steps in the respiratory burst of PMN. This suppressive action should be very useful in the prevention and treatment of reactive oxygen-associated disorders.
 ...
PMID:Suppression of respiratory burst of polymorphonuclear leukocytes by azelastine hydrochloride (Azeptin). 785

Interaction of Entamoeba histolytica trophozoites with fibronectin (FN) induces reorganization of the actin cytoskeleton and an increase in proteolytic activities that results in the degradation of the bound protein. The binding is mediated by a 37-kDa FN "receptor" localized in the trophozoite surface and associated to the cytoskeleton. The intracellular signals triggered by the ligand-receptor interaction are not well understood but it is plausible that they drive the observed responses. To address this issue, the activation of protein kinase C (PKC) pathways by FN binding was explored. Stimulation with phorbol myristate acetate (PMA) or FN produced a rapid increase in the amebas adhesion to the substrate and local release of proteases. Two PKC inhibitors, H7 and staurosporine, reverted the PMA stimulus and inhibited the response induced by FN. Interaction with FN as well as treatment with PMA produced transient changes of F-actin levels susceptible to inhibition by H7. Furthermore, phosphorylation of amebic proteins was enhanced in response to FN binding and PMA, while the presence of the PKC inhibitor diminished their phosphorylation. Inositol triphosphate production was stimulated by the FN binding, and PKC activation and translation was registered in cell extracts obtained from the stimulated amebas. Our results suggest that PKC pathways are activated in amebas by information transduced as a result of trophozoite binding to FN.
 ...
PMID:Entamoeba histolytica: PKC transduction pathway activation in the trophozoite-fibronectin interaction. 795 62

Female SENCAR mice were pre-fed a control or 40% energy-restricted (ER) diet with energy removed from fat and carbohydrate, or a control, balanced high fat (BHF, with similar energy from fat and carbohydrate), 35% energy restricted from fat (HCR) or 35% energy restricted from carbohydrate (HFR) diet. Epidermal cells were isolated by trypsin digestion for measurement of protein kinase C (PKC) activity, lipid composition or lipid metabolism. Dietary restriction of fat or carbohydrate energy (HFR or HCR group) reduced particulate PKC activity in epidermal cells compared with cells from control mice. The ratio of soluble particulate PKC activity was higher in epidermal cells from mice fed the HCR diet compared with those fed the HFR diet. Diet did not affect soluble PKC activity. Inositol accumulation was measured in the water- or lipid-soluble fractions of prelabeled ([3H]inositol) epidermal cells following a 1-h incubation in media with LiCl. Phosphatidylinositol, inositol biphosphate and inositol triphosphate fractions were more heavily labeled in cells from mice fed the ER diet. Energy restriction did not modify epidermal total lipid or phospholipid composition, but 1,2-diacylglycerol levels were elevated in relation to cell number in epidermal cells from mice fed the ER diet. These data suggest that dietary energy restriction modified PKC activity through a pathway other than alteration in membrane lipid composition or inositol lipid metabolism.
 ...
PMID:Protein kinase C activity is reduced in epidermal cells from energy-restricted SENCAR mice. 814 69

Intracellular Ca2+ responses to extracellular matrix molecules were studied in suspensions of pancreatic acinar cells loaded with Fura-2. Collagen type I, laminin, fibrinogen and fibronectin were unable to raise cytosolic free Ca2+ concentration ([Ca2+]i), whereas collagen type IV, at concentrations from 5 to 50 micrograms/ml, significantly increased it. The effect of collagen type IV was not due to possible contamination with type-I transforming growth factor beta or plasminogen, as neither of these agents was able to increase [Ca2+]i. Using highly specific mass assays, concentrations of inositol lipids, 1,2-diacylglycerol (DAG) and Ins(1,4,5) P3 were measured in pancreatic acinar cells stimulated with collagen type IV. A decrease in the concentrations of PtdIns(4,5) P2 and PtdIns4 P with a concomitant increase in the concentrations of DAG and InsP3 mass were observed, showing that collagen type IV increases [Ca2+]i by activation of phospholipase C. The observed [Ca2+]i signals had two components, the first resulting from Ca2+ release from the intracellular stores, and the second resulting from Ca2+ flux from the extracellular medium through the verapamil-insensitive channels. A tyrosine kinase inhibitor (tyrphostine) was able to block inositol lipid signalling caused by collagen type IV, which together with the insensitivity of this pathway to cholera toxin and pertussis toxin or to preactivation of protein kinase C, the longer duration of the increase in [Ca2+]i and a longer lag period needed for observation of increases in DAG and InsP3 concentration with collagen type IV than with carbachol (50 mM) suggest that activation of phospholipase C by collagen type IV is caused by tyrosine kinase activation. Inositol lipid signalling and increases in [Ca2+]i were also observed with Arg-Gly-Asp (RGD)-containing peptide but not with Arg-Asp-Gly (RDG)-containing peptide. Collagen type IV and RGD-containing peptide, but not carbachol, competed in increasing [Ca2+]i and DAG concentration, suggesting that the binding site of collagen type IV responsible for phospholipase C activation contains the RGD sequence. Together the present results suggest that, in pancreatic acinar cells, RGD sequence(s) within collagen type IV molecules cause activation of tyrosine kinase, probably through one of the integrin receptors, which then stimulates phospholipase C and increases [Ca2+]i.
 ...
PMID:Collagen type IV stimulates an increase in intracellular Ca2+ in pancreatic acinar cells via activation of phospholipase C. 819 49

The influence of oxidative stress on agonist-stimulated changes of intracellular free calcium and inositol trisphosphate in the neurosecretory PC12 cell line was investigated. The oxidant H2O2 modulated the bradykinin-induced calcium signal by decreasing the initial peak and the plateau phase in the same manner as tetraphorbolacetate, an activator of protein kinase C. Inositol trisphosphate formation, induced by bradykinin was also decreased by oxidative stress. Thiol protecting agents were able to restore the altered signal. In contrast to this, radical quenching substances had no influence on calcium signals in stressed cells. Inhibitors of several protein kinases, such as protein kinase C, protein kinase A, or cyclic GMP-dependent protein kinase showed the ability to protect the plateau phase of calcium signals against oxidative stress, but not the peak response. These results indicate that under the influence of oxidative stress multiple targets within the signal transduction cascades are affected.
 ...
PMID:Modulation of bradykinin-induced calcium signals by oxidative stress in PC12 cells. 821 40

Rat C6 glioma cells chronically acclimated to hypertonic media accumulate large quantities of inositol. When returned to isotonic conditions, the cells swell and lose inositol slowly via a four- to fivefold increase in the rate of passive inositol efflux. The inositol efflux pathway is a Na(+)-independent transport mechanism with low affinity for inositol and is inhibited by quinidine, quinine, various anion transport blockers, and cis-unsaturated fatty acids. Ionomycin-induced elevation of intracellular Ca2+ (Ca2+i) had no effect on basal or swelling-induced inositol efflux. Inositol efflux was not inhibited by chelation of Ca2+i with 1,2-bis(2-aminophenoxy)-ethane-N,N,N',N'-tetraacetic acid. In addition, Ca2+i measured with fura 2 did not change during cell swelling, indicating that increases in Ca2+i do not regulate inositol efflux. Exposure of C6 cells to 20 nM phorbol 12-myristate 13-acetate, 0.5 mM adenosine 3',5'-cyclic monophosphate (cAMP), or 50 microM forskolin had no effect on basal inositol efflux but stimulated swelling-induced inositol loss by 2.6-, 2.2-, and 3.4-fold, respectively. Exposure to the protein kinase inhibitors 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine or staurosporine or downregulation of protein kinase C (PKC) activity, however, had no inhibitory effect on inositol efflux, and cellular cAMP levels were not altered by cell swelling. Taken together, these results indicate that stimulation of PKC and protein kinase A modulates the activity of the efflux pathway but is not required for swelling-induced activation. Ketoconazole, cinnamyl-3,4-dihydroxy-alpha-cyanocinnamate, and gossypol, inhibitors of lipoxygenase enzymes, blocked both basal and swelling-induced inositol efflux, suggesting indirectly that lipoxygenase metabolites may be responsible for swelling-induced activation of the efflux mechanism. The characteristics of inositol efflux in C6 cells are similar to those described for volume regulatory sorbitol and taurine efflux in a number of cell types, suggesting the existence of a common transport mechanism.
 ...
PMID:Mechanism and regulation of swelling-activated inositol efflux in brain glial cells. 839 81

Clinical trials demonstrate that up to 70% of neural tube defects (NTDs) can be prevented by folic acid supplementation in early pregnancy, whereas the remaining NTDs are resistant to folate. Here, we show that a second vitamin, myo-inositol, is capable of significantly reducing the incidence of spinal NTDs in curly tail mice, a genetic model of folate-resistant NTDs. Inositol increases flux through the inositol/lipid cycle, stimulating protein kinase C activity and upregulating expression of retinoic acid receptor beta, specifically in the caudal portion of the embryonic hindgut. This reduces the delay in closure of the posterior neuropore, the embryonic defect that is known to lead directly to spina bifida in curly tail embryos. Our findings reveal a molecular pathway of NTD prevention and suggest the possible efficacy of combined treatment with folate and inositol in overcoming the majority of human NTDs.
 ...
PMID:Inositol prevents folate-resistant neural tube defects in the mouse. 898 32

Inositol 3,4,5,6-tetrakisphosphate is a novel intracellular signal that regulates calcium-dependent chloride conductance (Xie, W., Kaetzel, M. A., Bruzik, K. S., Dedman, J. R., Shears, S. B., and Nelson, D. J. (1996) J. Biol. Chem. 271, 14092-14097). The molecular mechanisms that regulate the cellular levels of this signal are not characterized. To pursue this problem we have now studied the 1-kinase that deactivates inositol 3,4,5,6-tetrakisphosphate. The enzyme was purified from rat liver 1600-fold with a 1% yield. The native molecular mass was determined to be 46 kDa by gel filtration. The Km values for inositol 3,4,5,6-tetrakisphosphate and ATP were 0. 3 and 10.6 microM, respectively. The kinase was unaffected by either protein kinase A or protein kinase C. Increases in Ca2+ concentration from 0.1 to 1-2 microM inhibited activity by 10-20%. Most importantly, inositol 1,3,4-trisphosphate was shown to be a potent (Ki = 0.2 microM), specific, and competitive inhibitor of the 1-kinase. Our new kinetic data show that typical receptor-dependent adjustments in cellular levels of inositol 1,3,4-trisphosphate provide a mechanism by which the concentration of inositol 3,4,5,6-tetrakisphosphate is dependent on changes in phospholipase C activity. These conclusions also provide a new perspective to our understanding of the physiological importance of the pathway of inositol phosphate turnover initiated by the inositol 1,4, 5-trisphosphate 3-kinase.
 ...
PMID:Properties of the inositol 3,4,5,6-tetrakisphosphate 1-kinase purified from rat liver. Regulation of enzyme activity by inositol 1,3,4-trisphosphate. 899 35

This study investigated the mechanism of protein kinase C-mediated inhibition of ATP-induced phospholipase C activation in cultured bovine aorta endothelial cells (BAEC). In BAEC labeled with 3H-inositol, phorbol myristate acetate (PMA) prevented ATP-induced inositol bisphosphate and inositol trisphosphate formation. In membranes prepared from these PMA-treated cells, Ca(2+)-, sodium fluoride-, GTP gamma S-, and ATP plus GTP gamma S-stimulated inositol bisphosphate, but not inositol trisphosphate, formation was inhibited. Inositol trisphosphate phosphatase activity was not altered in membranes from PMA-treated BAEC. These results suggest that 1) protein kinase C inhibits ATP-induced phospholipase C activation in BAEC through interference with the coupling of phospholipase C with a G-protein and through an effect on phospholipase C itself, and 2) different mechanisms are responsible for the inhibition by protein kinase C of the phospholipase C-mediated hydrolysis of phosphatidylinositol bisphosphate and phosphatidyl-inositol phosphate.
 ...
PMID:Protein kinase C regulation of ATP-induced phosphoinositide hydrolysis in bovine aorta endothelial cells. 936 31

Keratinocytes produce vitamin D3, metabolize it to its most biologically active form, 1,25-dihydroxyvitamin D3 (1,25[OH]2D3), and respond to the 1,25(OH)2D3 they produce with a decrease in proliferation and an increase in differentiation. 1,25(OH)2D3 production by keratinocytes is tightly controlled and changes as the cells differentiate, increasing during the early stages of differentiation, then decreasing again as terminal differentiation ensues. The 1,25(OH)2D3 produced endogenously or supplied exogenously acts in concert with calcium to stimulate the transition from a proliferating basal cell to a terminally differentiated corneocyte. The mRNA levels for proteins involved in the differentiation process are controlled not only by calcium- and 1,25(OH)2D3-induced increase in gene transcription, but by subsequent calcium- and 1,25(OH)2D3-induced destabilization of the mRNA after adequate levels of the proteins have been produced. 1,25(OH)2D3 increases intracellular calcium in part by inducing phospholipase C, which when activated by hormones, cleaves phosphoinositol bisphosphate into two important signaling molecules inositol tris phosphate and diacylglycerol. Inositol tris phosphate releases intracellular calcium from intracellular stores, and the increase in intracellular calcium opens up the nonspecific cation channel through which calcium enters the cell. Diacylglycerol and intracellular calcium promote protein kinase C activity that can further enhance the differentiation process. These actions of 1,25(OH)2D3 provide the rationale for the effectiveness of 1,25(OH)2D3 and its analogs in psoriasis.
 ...
PMID:1,25(OH)2D3-modulated calcium induced keratinocyte differentiation. 962 87


<< Previous 1 2 3 4 5 6 7 Next >>