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 have studied the effect of protein kinase C inhibitors 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H7) and calphostin C on the cycle of Neuro-2a cells. Both compounds inhibited cell proliferation and DNA synthesis. Transition from G2 to M phase was not altered by these compounds. Calphostin C blocked the cells in G0/G1, while H7 did not at any specific point in the cell cycle. We also show that the antiproliferative effect induced by both inhibitors is reversible.
 ...
PMID:Differential effects of the protein kinase C inhibitors H7 and calphostin C on the cell cycle of neuroblastoma cells. 128 43

DJM-1 cells (a human squamous cell carcinoma cell line) grown in low Ca2+ medium did not form cell-cell junctions of desmosome-keratin intermediate filament (KIF). When they were shifted to normal (high) Ca2+ medium, rapid translocation of desmoplakins from the cytosol to the plasma membrane to form desmosomes and reorganization of 180 kd-hemidesmosome proteins were induced almost simultaneously. In correlation with these morphological responses, the Ca2+ shift caused a breakdown of inositol phospholipids, a formation of diacylglycerol (DAG) and inositol trisphosphate (IP3), protein kinase C (PKC) activation, and Ca2+ influx. 12-0-tetradecanoylphorbol-13-acetate (TPA)-treatment of low Ca(2+)-grown DJM-1 cells also caused desmosome formation in association with PKC activation. These TPA effects were cancelled with PKC inhibitors, 1-(5-isoquinolinylsulfomyl)-2-methylpiperazine (H7) and staurosporine. Treatment with other PKC-activating agents, phorbol-12,13-butyrate (PDBu) and diaoctanoylglycerol (DOG), also induced desmosome formation. TPA-treatment of normal Ca(2+)-grown cells collapsed the organized distribution of the 180 kd-hemidesmosome protein and appeared to detach this protein from the cell-matrix adhering sites. This effect was also inhibited by H7. These results suggest that PKC activation plays important roles in upregulation of cell-cell junctions and downregulation of cell-matrix junctions in association with differentiation of keratinocytes.
 ...
PMID:Control of the distribution of hemidesmosome components in cultured keratinocytes: Ca2+ and phorbol esters. 128 69

[Met5]-Enkephalin (ME) secretion and the expression of proenkephalin A (proENK) mRNA were studied following long-term exposure of bovine adrenal medullary chromaffin (BAMC) cells to pertussis toxin. Treatment with pertussis toxin for 24 h increased the secretion of ME in a concentration- and time-dependent manner. The magnitude of ME secretion continued to increase with time in the presence of pertussis toxin. The intracellular concentration of ME in the pertussis toxin-treated group was not significantly different from controls, suggesting that elevated levels of ME secretion result from increased biosynthesis of ME rather than from release of stored ME. Prolonged (24 h) stimulation of BAMC cells with pertussis toxin also increased proENK gene expression. Pretreatment with nimodipine (a calcium channel blocker) and calmidazolium (a calmodulin antagonist) inhibited both the secretion of ME and the increase in proENK mRNA levels induced by pertussis toxin, while the intracellular calcium antagonist dantrolene and the protein kinase C inhibitors sphingosine and H7 [1-(5-isoquinolinylsulfonyl)-2-methylpiperazine] were ineffective in blocking pertussis toxin-induced responses. Forskolin (an adenyl cyclase activator) and isobutyl methyl xanthine (a phosphodiesterase inhibitor) increased both ME secretion and proENK mRNA levels; pertussis toxin synergistically increased the secretion of ME with these cyclic AMP-elevating agents but had only an additive effect with these agents on the level of proENK mRNA. Our results suggest that a pertussis toxin-sensitive G protein may tonically regulate the secretion of ME as well as the level of proENK mRNA.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Pertussis toxin stimulates the secretion of [Met5]-enkephalin and the expression of proenkephalin A mRNA in bovine adrenal medullary chromaffin cells. 128 24

The normal mouse mammary epithelial cells, NOG-8, respond to the mitogenic signal of prolactin with a 2.5-fold increase in cell number within 3 days in vitro. When prolactin is added to subconfluent cells for 5-15 min, there is a 5-fold increase in protein kinase C activity. Upon longer exposure (24 h) to the hormone, the enzyme activity returns to that of control. The potent protein kinase C inhibitor, 1-(5-isoquinolinesulfonyl)-2-methylpiperazine dihydrochloride (H7), blocks both the prolactin-induced enzyme activity and subsequent increase in cell number. Prior to prolactin treatment, 90% of the protein kinase C activity resides in the cytosol with only 10% associated with the membranes. After only 5 min of prolactin treatment, 70% of the enzyme activity is now localized to the membranes. These data suggest that prolactin uses the protein kinase C pathway for signal transduction in NOG-8 cells thus leading to enhanced cell growth.
 ...
PMID:Prolactin-induced protein kinase C activity in a mouse mammary cell line (NOG-8). 130 98

We have investigated phospholipase D activity in rat brain cortical slices prelabeled with [32P]orthophosphoric acid. In the presence of ethanol (170 mM), norepinephrine stimulated, in a dose-dependent manner (EC50 = 2.2 microM), the accumulation of [32P]phosphatidylethanol as a result of phospholipase D activity. Norepinephrine-stimulated phospholipase D activity was completely inhibited by prazosin, a specific alpha 1-adrenergic antagonist (Ki = 2.8 nM). However, no accumulation of phosphatidylethanol was observed in the presence of the muscarinic agonist carbachol. The Ca2+ ionophore ionomycin and the protein kinase C activator phorbol 12-myristate 13-acetate (PMA) also stimulated [32P]phosphatidylethanol accumulation in cortical slices, in a dose- and time-dependent manner, whereas the inactive phorbol, 4 alpha-phorbol 12,13-didecanoate, did not stimulate phospholipase D activity. Staurosporine and 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine, two potent inhibitors of protein kinase C, inhibited PMA and ionomycin stimulation of phospholipase D activity, but did not affect the response to norepinephrine. Furthermore, the effects of PMA and norepinephrine were additive. Differences between PMA and norepinephrine stimulation of phospholipase D activity were also found with regard to the extracellular Ca2+ requirement and time course of phosphatidylethanol accumulation. No stimulation of phospholipase D activity by norepinephrine was observed in slices from cerebellum, a brain area with a low density of alpha 1-adrenergic receptors, while the effect of PMA was greater in the cerebellum than in cortical or hippocampal slices. These results strongly suggest that activation of phospholipase D in cortical slices by norepinephrine and PMA involve different mechanisms.
 ...
PMID:Alpha 1-adrenergic receptor-mediated activation of phospholipase D in rat cerebral cortex. 131 Sep 79

We have tested if inhibition of protein kinase C is able to prevent and/or to restore the decrease of Na+,K(+)-ATPase activity in the sciatic nerve of alloxan-induced diabetic mice. Mice were made diabetic by subcutaneous injection of 200 mg of alloxan/kg of body weight. The activity of Na+,K(+)-ATPase decreased rapidly (43% after 3 days) and slightly thereafter (58% at 11 days). We show that intraperitoneal injection of 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H7), an inhibitor of protein kinase C, prevents completely the loss of Na+,K(+)-ATPase activity produced by alloxan. Also, H7 injected into diabetic mice, 4-9 days after the injection of alloxan, restores the activity of the enzyme. The amount of activity recovered depends on the dose of H7 administered; complete recovery was reached with injection of 15 mg of H7/kg of body weight. The effect of H7 is transient, with a half-life of approximately 1 h.
 ...
PMID:Inhibition of protein kinase C restores Na+,K(+)-ATPase activity in sciatic nerve of diabetic mice. 131 72

Using the human hepatoma cell line Hep G2, we have studied a possible role of protein kinase C (PKC) activity for regulation of erythropoietin (EPO) production. During a 72-h incubation, EPO production by the cells was stimulated sevenfold by exposure to low oxygen tension (1%) and threefold by exposure to cobaltous chloride (100 microM). The phorbol ester phorbol 12-myristate-13 acetate (PMA) led to a concentration-dependent inhibition of basal and stimulated EPO formation (ED50 10 nM). This decrease of EPO production, which was apparent already after 1 h of incubation with PMA, reached its maximal effect after 24 h and held on for 72 h. It was paralleled by an inhibition of the increase of EPO mRNA levels in response to stimulation. A 24-h preincubation of the cells with PMA (100 nM) virtually blunted the effect of hypoxia on EPO formation. Recovery of EPO synthesis after removal of PMA took 48-72 h. The effect of PMA on EPO production was mimicked by phorbol 12,13-dibutyrate (ED50 1 microM) but not by 4 alpha-phorbol 12,13-didecanoate. The synthetic diacylglycerol analogues oleolyl-acetylglycerol and dioctanoylglycerol (2-200 microM) also had no effect on either basal or stimulated EPO production. Treatment with PMA caused a translocation of the alpha-isoenzyme of PKC from the cytosol to the membrane after 1 h and a disappearance of the membrane-bound form after 24 h of incubation. Staurosporine and 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine, two structurally different inhibitors of PKC activity, inhibited basal and stimulated EPO production with ED50 values of 9 nM and 50 microM, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Phorbol ester inhibits erythropoietin production in human hepatoma cells (Hep G2). 131 1

At concentrations between 2 and 32 mM, ethanol is shown to depress human platelet cAMP levels. The effect is biphasic, maximal at 30 sec, with platelet concentrations of cAMP returning to baseline values at higher ethanol concentrations and at longer incubation times. The cAMP lowering effect of ethanol can be blocked by a phosphodiesterase (PPDE) inhibitor, 3-isobutyl-1-methyl-xanthine (IBMX), at a concentration of 2 mM, suggesting that an increase in PPDE activity may be responsible for this effect. Exposure of platelets to 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H7), a protein kinase C (PKC) inhibitor, blocks the ethanol-induced decrease in platelet cAMP, suggesting ethanol may be acting through activation of PKC.
 ...
PMID:Ethanol exposure results in a transient decrease in human platelet cAMP levels: evidence for a protein kinase C mediated process. 131 34

To evaluate the influence of protein kinase C (PKC) activation on Na/K-ATPase activity in MDCK cells, we studied the effect of phorbol myristate acetate (PMA) and two diacylglycerol analogues, oleoylacetylglycerol and dioctanoylglycerol, on the enzyme activity. Na/K-ATPase activity was determined by cytochemistry. PMA induced a time- and dose-dependent inhibition of Na/K-ATPase activity and at 100 ng/ml decreased the enzyme activity by 55% of the initial value. These effects were mimicked by oleoylacetylglycerol and dioctanoylglycerol, and were abolished by two inhibitors of PKC, 1-(5-isoquinolinylsulphonyl)-2-methylpiperazine (H7) and sphingosine. A phorbol ester that does not activate PKC, 4 alpha-phorbol 12,13-didecanoate, did not inhibit Na/K-ATPase activity. PMA inhibition persisted in the presence of cycloheximide and actinomycin D but not in the presence of amiloride. Dopamine (10 microM) inhibition of Na/K-ATPase activity was abolished in a dose-dependent manner by sphingosine. Results suggest that in MDCK cells Na/K-ATPase is an effector protein for PKC and that dopamine inhibition of its activity may be mediated by PKC.
 ...
PMID:Protein kinase C activation causes inhibition of Na/K-ATPase activity in Madin-Darby canine kidney epithelial (MDCK) cells. 131 49

The receptor for gp70 envelope glycoprotein of murine ecotropic leukemia virus is essential for virus entry into the host cell and has been recently demonstrated to function as a cationic amino acid transporter. In the experiments reported herein, we compared the gene expression of the murine ecotropic retroviral receptor (ERR) and its human homolog (H13) in rapidly proliferating cells versus resting cells using four different systems. (i) The expression of ERR gene is enhanced during activation of T and B lymphocytes by concanavalin A and lipopolysaccharide, respectively. Similar enhancement is observed by adding phorbol 12-myristate 13-acetate (PMA) or calcium ionophore (A23187). These phenomena appear to involve protein kinase C; two PMA analogs, 4 alpha-phorbol and 4 alpha-PMA, lacking the ability to activate protein kinase C fail to induce elevated levels of gene expression, and the protein kinase C inhibitor, H7 [1-(5-isoquinolinylsulfonyl)-2-methylpiperazine dihydrochloride[, inhibits the enhancement induced by PMA. (ii) Friend murine leukemia virus induces rapid splenomegaly, and acute erythroleukemia in sensitive mice. Concomitantly with splenomegaly, ERR gene expression in spleen cells increases dramatically. (iii) The level of expression of the ERR or H13 gene in a variety of tumor cells is highly elevated compared with the level in noncancerous cells. (iv) H13 gene expression decreases upon terminal differentiation of the human promyelocytic leukemia cell line HL-60 into granulocytes or macrophages by dimethyl sulfoxide or PMA, respectively. These results suggest that ERR and H13 genes play an important role in cellular proliferation.
 ...
PMID:Enhanced gene expression of the murine ecotropic retroviral receptor and its human homolog in proliferating cells. 131 7


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