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)

Tissue-type plasminogen activator (tPA) is secreted by rat granulosa cells in response to treatment with activators of protein kinase A (follitropin, FSH), protein kinase C (gonadotropin-releasing hormone, GnRH) and tyrosine kinase (epidermal growth factor, EGF). Because steroid hormones have been shown to enhance the gonadotropin stimulation of ovarian differentiation, we investigated the effects of steroid hormones, alone or together with various kinase activators, on tPA activities and mRNA levels in cultured rat granulosa cells. Treatment of cells with dexamethasone (DEX; a glucocorticoid agonist) or R1881 (an androgen agonist) caused an increase in tPA secretion and mRNA levels. In addition, the stimulation of tPA activity and mRNA levels by FSH (50 ng/ml) was synergistically enhanced by cotreatment with DEX or R1881 in a time-dependent manner with 2.8- and 1.6-fold increase at 9 h after incubation as compared to cells treated with FSH alone. In contrast, treatment with diethylstilbestrol had no effect on tPA levels. Furthermore, tPA activity and mRNA levels induced by GnRH and EGF were also increased by cotreatment with DEX or R1881 as compared with cells treated with GnRH or EGF alone. Likewise, the stimulation of tPA mRNA levels by dibutyryl cAMP, a protein kinase A activator, and phorbol myristate acetate (PMA), a protein kinase C activator, was enhanced by cotreatment with DEX or R1881. These results demonstrate that glucocorticoid and androgen enhance tPA secretion and mRNA levels stimulated by FSH, GnRH and EGF in granulosa cells. The rat granulosa cells provide a useful model for studying the mechanism of regulation of tPA gene expression by steroid hormones.
 ...
PMID:Synergistic effect of glucocorticoids and androgens on the hormonal induction of tissue plasminogen activator activity and messenger ribonucleic acid levels in granulosa cells. 210 7

The effect of increasing intracellular free calcium and activating protein kinase C on glucocorticoid receptor (GR) expression was investigated in AtT-20 cells, a mouse corticotrope tumor cell line. Treatment of AtT-20 cells with the calcium ionophore A23187 induced a rapid time- and dose-dependent decrease in [3H]dexamethasone ([3H]DEX) binding when measured in intact cells. Binding fell to 16% of control following 3 h of treatment with 10 microM A23187. In contrast, A23187 did not acutely effect steady state levels of GR mRNA, although levels fell to 76 +/- 1% of control after 8-15 h of treatment. Scatchard analysis of A23187 treated cultures demonstrated a decrease in GR binding capacity but no change in affinity for [3H]DEX. Acute inhibition of protein synthesis with cycloheximide had no effect on [3H]DEX binding, suggesting that the calcium-dependent decrease was not simply due to inhibition of GR protein synthesis. In contrast to the A23187 induced decrease in [3H]DEX binding in intact cells, when binding was measured in cytosol extract from A23187 treated cultures there was no decrease. These data suggest that the A23187 induced decrease in GR binding in whole cells is not due to a decrease in GR protein but reversible conversion of the receptor to a non-binding form. Inducing calcium influx only through L-type voltage-dependent calcium channels with BAY K8644 also decreased [3H]DEX binding at AtT-20 cells, though the effect was less than that induced by A23187. Although activation of protein kinase C with phorbol ester transiently increases intracellular free calcium in AtT-20 cells, when cells were treated for 0.5 to 22 h with phorbol 12-myristate 13-acetate, there was no acute fall in [3H]DEX binding, and only a small decrease following 16 h of treatment. These data demonstrate that sustained increases in intracellular calcium in corticotropes can induce a rapid and marked decrease in GR binding. The mechanism is post-translational and involves the reversible conversion of the receptor to a non-binding form. In addition, the cellular milieu is clearly important in conferring non-binding status on GR since once the cell is disrupted GR binding is restored.
 ...
PMID:Calcium and protein kinase C regulation of the glucocorticoid receptor in mouse corticotrope tumor cells. 751 9

The respective roles of protein kinase C (PKC) and intracellular calcium concentration ([Ca2+]i) in glucocorticoid (GC) action on prostacyclin (PGl2) production by bovine aortic endothelial cells (BAEC) were investigated. Twenty-four hours' pretreatment with dexamethasone (DEX, 10(-6) diminished the response of BAEC to calcium ionophore A23187 (0.001-1 micrograms/ml) and ionomycin (3 microM) by about 50%, as assessed by both PGl2 release and [Ca2+]i elevation. Contrary to control cells, in DEX-penetrated cells short treatment with 12-O-tetradecanoyl phorbol 13-acetate (100 nM) significantly decreased PGl2 production without affecting cyclooxygenase activity. The data suggest that the mechanism of action of GC involves both pathways of intracellular signal transduction, namely the rises in both [Ca2+]i and PKC activity. These actions of DEX may be attributed to a phospholipase A2-inhibiting protein, such as lipocortin, which accumulates during exposure to DEX. Binding of a sufficient fraction of calcium ions and phosphorylation by PKC might be the events needed fro lipocortin activation.
 ...
PMID:Glucocorticoids regulate both phorbol ester and calcium ionophore-induced endothelial prostacyclin synthesis. 904 29

We tested the relative efficacy of free dexamethasone, dexamethasone containing liposomes and free liposomes in preventing superoxide anion, O-2 generation by neutrophils. O-2 production by 5 x 10(5) neutrophils, whether primed or not with lipopolysaccharide, was stimulated by phorbol 12-myristate 13-acetate (PMA) to 13.4 +/- 1.3 nmoles after 15 minutes compared to 1.2 +/- 0.3 nmoles with nonstimulated cells. Free liposomes but not dexamethasone (dexa) decreased non-stimulated as well as PMA-induced O-2 generation. Dexa-containing phosphatidylcholine from egg yolk: phosphatidylserine from bovine brain (PC:PS 7:3) liposomes, unlike free dexa, diminished PMA-stimulated O-2 production in a dose-dependent manner with a maximal effect at 37.5 micrograms/ml phospholipid (6.6 +/- 1.6 nmoles). The kinetics of cytochrome-c reduction revealed that decreased O-2 production resulted from an extended lag-time of release to almost 8 minutes with PMA induction and consequently led to the conclusion that liposomes modified the activity of NADPH oxidase as well as that of protein kinase C. Liposomes prepared with PC and PS of natural origin had a greater inhibitory effect on O-2 generation by neutrophils than dipalmitoylphosphatidylcholine (DPPC) and phosphatidylethanolamine from egg yolk (PE):PC (3:1) liposomes. When 100 microM of Ca2+ was added to the medium, the inhibitory action of liposomes prepared with egg yolK PC and DPPC was increased by 30 and 60% respectively, while that of PS and PE:PC was prevented. We also verified that liposomes by themselves, even if phagocytized, did not induce O-2 generation or its concentration was too low to be detected by this technique. From the clinical point of view, some formulations delayed non-induced and PMA-induced O-2 generation, thus adding to the anti-inflammatory effect of the glucocorticoid they transported.
 ...
PMID:Modulation of noninduced and phorbol ester-induced generation of superoxide anion by free liposomes and liposomes containing dexamethasone. 904 63

The signaling pathways involved in the regulation of glucocorticoid on Pi uptake were examined in primary cultured rabbit renal proximal tubule cells (PTCs). Dexamethasone (DEX, 10(-9) M) inhibited Pi uptake, although aldosterone, a mineralocorticoid, did not affect Pi uptake. Its effect was due to a 23% decrease in the V(max) value. DEX-induced inhibition of Pi uptake was prevented by actinomycin D, cycloheximide, and the glucocorticoid receptor antagonists, progesterone and cortexolone. SQ 22536 (adenylate cyclase inhibitor) and the myristoylated protein kinase A inhibitor amide 14-22 (PKI) did not block the DEX-induced inhibition of Pi uptake. Indeed, DEX did not affect cAMP production. However, neomycin and U 73122 (PLC inhibitors), staurosporine and bisindolylmaleimide I (PKC inhibitors) blocked the DEX-induced inhibition of Pi uptake. In addition, DEX increased the membrane-bound PKC activity from 2. 82+/-0.21 to 4.16+/-0.34 pmol/mg protein/min. These findings demonstrate that glucocorticoid inhibits Pi uptake and its effect is genomic and receptor-mediated and the activation of the PLC/PKC pathway is involved in its effect on the PTCs.
 ...
PMID:Regulatory mechanisms of Na/Pi cotransporter by glucocorticoid in renal proximal tubule cells: involvement of cAMP and PKC. 1056 47

In rat astrocytes, forskolin (FSK; 5 microM) and phorbol-12-myristic-13-acetate (PMA; 2.5 microM) increase the proenkephalin (proENK) mRNA level via different pathways. FSK-induced proENK mRNA expression is independent of protein de novo synthesis, and well correlated with CREB phosphorylation. This is in contrast to PMA-induced proENK mRNA expression that is dependent on protein de novo synthesis and is well correlated with the increase of AP-1 DNA binding activity rather than CREB phosphorylation. Differential regulation of AP-1 proteins by PMA and FSK was also observed. While c-Fos, Fra-2 and JunB were increased in response to either stimuli, only Fra-1, c-Jun and JunD were increased by PMA. The combined treatment with FSK and PMA additively increased the proENK mRNA level, which was correlated with AP-1 or ENKCRE-2 DNA binding activity, and CREB phosphorylation. Dexamethasone (DEX; 1 microM) further enhanced FSK- or PMA-induced proENK mRNA expression, which was not correlated with the activation of AP-1 expression and CREB phosphorylation, suggesting that synergistic interaction of glucocorticoid with PKA or PKC pathway for the regulation of proENK mRNA expression appears to be mediated by other pathways rather than CREB and AP-1 families.
 ...
PMID:The differential molecular mechanisms underlying proenkephalin mRNA expression induced by forskolin and phorbol-12-myristic-13-acetate in primary cultured astrocytes. 1111 30