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)

The role of growth hormone (GH) in the differentiation process of Ob1771 mouse preadipocyte cells has been studied under culture conditions that were serum-free and hormone-supplemented and which were previously shown to lead to terminal differentiation. In the absence of GH, a dramatic decrease in the adipogenic activity of the culture medium could be observed, as indicated 12 days after confluence by the low levels of glycerol-3-phosphate dehydrogenase activity and the sharp reduction of the number of triacylglycerol-containing cells. This decrease in adipogenic activity was accompanied by a parallel loss of the mitogenic potency of the culture medium. Determination of the half-maximal and maximal concentrations of GH required for the restoration of growth and differentiation were identical, 0.5 and 2 nM, respectively. Despite the presence of insulin-like growth factor-I (IGF-I) to substitute for supraphysiological concentrations of insulin and to saturate IGF-I receptor, GH was still required to induce terminal differentiation of a maximal number of cells. However, protein kinase C activators such as prostaglandin F2 alpha, phorbol esters and diacylglycerol were able to mimic GH in promoting a maximal mitogenic-adipogenic response, indicating that the ability of GH to induce diacylglycerol production (Doglio et al., 1989; Catalioto et al., 1990) plays a prominent role in this process. Furthermore, in agreement with the fact that the mitoses which precede terminal differentiation of Ob1771 preadipocytes are strictly controlled by cAMP and only modulated by protein kinase C, terminal differentiation of Ob1771 preadipocytes occurred in the absence of GH upon supplementation with high concentrations of carbaprostacyclin, added as a cAMP-elevating agent or with 8-Br-cAMP, added as a cAMP analogue. It is concluded that the control exerted by GH on terminal differentiation of mouse preadipocytes corresponds to a modulating mitogenic effect mediated through protein kinase C activation and leading to a potentiation of the cAMP and IGF-I mitogenic signalling pathways.
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PMID:Terminal differentiation of mouse preadipocyte cells: the mitogenic-adipogenic role of growth hormone is mediated by the protein kinase C signalling pathway. 138 31

Following the differentiation of 3T3-L1 fibroblasts by insulin/dexamethasone/methylisobutylxanthine, marked increases in cAMP levels by isoproterenol but not forskolin and in 2-deoxyglucose uptake by insulin occurred. Pertussis toxin-pretreatment prior to addition of insulin/dexamethasone/methylisobutylxanthine and exposure of cells to pertussis toxin during differentiation attenuated glycerophosphate dehydrogenase activity as a differentiation marker enzyme and the responses to isoproterenol and insulin by approximately 50% of those in pertussis toxin-untreated cells. On the other hand, insulin/dexamethasone/methylisobutylxanthine caused induction of c-fos proto-oncogene in confluent 3T3-L1 fibroblasts. This induction was also reduced in pertussis toxin-pretreated cells. These results suggested that pertussis toxin-sensitive GTP-binding protein(s) is involved in expression of c-fos mRNA accompanied by differentiation. In addition, accumulation of c-fos mRNA by insulin/dexamethasone/methylisobutylxanthine was enhanced in protein kinase C-depleted cells pretreated with phorbol 12-myristate 13-acetate, indicating that protein kinase C may negatively regulate c-fos expression induced by insulin/dexamethasone/methylisobutylxanthine.
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PMID:Possible involvement of pertussis toxin-sensitive GTP-binding protein(s) in c-fos expression during differentiation of 3T3-L1 fibroblasts to adipocytes. 170 43

The tricyclic antidepressant desipramine, when added to culture medium, gave rise in C6 rat glioma cells to a decrease of the activity of the enzyme asialofetuin sialyltransferase. The inhibition was dose and time dependent and was observed in both multiplying cells and cells blocked with 2 mM thymidine or depletion of amino acids. This inhibition was rather specific to the sialyltransferase, as under the conditions where this enzyme was inhibited up to 70%, other enzymes such as dolichol phosphate mannose synthetase, glutamine synthetase, and glycerol phosphate dehydrogenase remained unaffected. This inhibition was not reversed after removal of desipramine from the medium and was not observed by direct addition of desipramine to the sialyltransferase incubation assay. Under the same conditions, W-7 [N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide], which is known to be a potent calmodulin antagonist and an inhibitor of calmodulin-dependent kinases, gave the same concentration-dependent inhibition profile of sialyltransferase as desipramine, whereas H-7 [1-(5-isoquinolinylsulfonyl)-2-methylpiperazine], which is an inhibitor of protein kinase C and cyclic nucleotide-dependent kinases, had no effect. So, it is suggested that desipramine inhibits the sialyltransferase activity in C6 glioma cells through a calmodulin-dependent system.
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PMID:Effect of desipramine on a glycoprotein sialyltransferase activity in C6 cultured glioma cells. 229 42

The terminal adipose differentiation of Ob1771 cells, characterized by glycerol-3-phosphate dehydrogenase activity and triacylglycerol accumulation, was studied in serum-free hormone-supplemented medium containing growth hormone, tri-iodothyronine, insulin, transferrin and fetuin. Arachidonic acid was able to substitute for a crude adipogenic fraction isolated from fetal bovine serum but not for growth hormone or tri-iodothyronine. Arachidonic acid was also able to increase in a rapid and dramatic manner cyclic AMP production; moreover it was able to amplify the adipose conversion promoted by other agents elevating cyclic AMP concentrations and to induce inositol phospholipid breakdown. Both phorbol 12-myristate 13-acetate, a protein kinase C activator and ionomycin, a Ca2+-mobilizing agent, showed potent synergy with agents elevating cyclic AMP concentrations for the promotion of adipose conversion, whereas 8-bromo cyclic GMP and 4 alpha-phorbol 12,13-dibutyrate were ineffective. The triggering of both the cyclic AMP and inositol phospholipid pathways was accompanied by a single round of cell division, and within a few days all the cells became differentiated. Similar results were obtained, after exposure to arachidonic acid, with preadipose 3T3-F442A cells and with rat adipose precursor cells in primary culture. The availability of arachidonic acid from intracellular stores and/or of exogenous origin should play a major role for the onset of critical mitoses leading to terminal differentiation in pre-adipose cells.
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PMID:Requirement and role of arachidonic acid in the differentiation of pre-adipose cells. 253 84

Insulin exposure stimulates an increase in glycerol-3-phosphate dehydrogenase (G3PDH) activity in isolated human lymphocytes that correlates to an increase in G3PDH mRNA and requires new protein synthesis. Synthetic diacylglycerol or phorbol ester can mimic the effect of insulin on G3PDH activity, suggesting that protein kinase C may be involved in regulation of G3PDH levels. In addition, lithium chloride, an inositol phosphate phosphatase inhibitor, and calcium uptake inhibitors can abolish insulin stimulation of G3PDH activity. For obese subjects in whom insulin resistance in vitro can be demonstrated, the extent of insulin stimulation of G3PDH activity is decreased compared to normal weight individuals, and treatment by a very low calorie diet restores insulin stimulation of G3PDH activity. Thus, insulin stimulation of G3PDH activity is dependent upon the metabolic state of the subject from whom the cells are obtained.
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PMID:Glycerol-3-phosphate dehydrogenase activity in human lymphocytes: effects of insulin, obesity and weight loss. 785 62

Insulin/dexamethasone/methylisobutylxanthine (hormones/IBMX) induce 3T3-L1 fibroblasts to differentiate into adipocytes. Our previous study suggested that pertussis toxin (IAP)-sensitive GTP-binding protein(s) (G-protein) is involved in the process of differentiation by hormones/IBMX, accompanied by c-fos induction. Northern blotting indicated that among the IAP-sensitive G-proteins, the levels of Gi2 alpha, Go alpha, and Gi3 alpha mRNA were decreased, increased and unchanged, respectively. Gi1 alpha was undetectable and IAP attenuated the decrease in Gi2 alpha mRNA level but did not affect the change in Go alpha mRNA level during the adipocyte differentiation. These results indicate that IAP-sensitive Gi2 alpha mRNA level is decreased during adipocyte differentiation. A combination of phosphatidylinositol-specific phospholipase C (PI-PLC) and IBMX induced c-fos expression in 3T3-L1 fibroblasts similar to that induced with hormones/IBMX. c-fos induced by both stimulators was also diminished by anti-inositolglycan antibody or anti-PI-PLC antiserum. Insulin stimulated the release of inositolproteoglycan and diacylglycerol from 3T3-L1 fibroblasts, which was suppressed by IAP treatment. These findings suggested that one of the pathways of adipocyte differentiation induced by hormones/IBMX occurs via the inositolglycan-specific PI-PLC cascade coupled to IAP-sensitive G-protein(s). Both activation of glycerophosphate dehydrogenase and stimulation of insulin-dependent 2-deoxyglucose uptake induced by hormones/IBMX were enhanced in protein kinase C-depleted cells exposed to phorbol 12-myristate 13-acetate (PMA), and attenuated in IAP-treated cells. The level of a 32P-labeled 52 kDa protein in plasma membrane fractions immunoprecipitated by anti-PI-PLC antiserum was increased by PMA stimulation, abolished in PMA-treated cells, and increased in IAP-treated cells. These findings suggest that protein kinase C phosphorylates PI-PLC, resulting in a decrease in PI-PLC activity related to the signal transduction pathway of adipocyte differentiation of 3T3-L1 fibroblasts.
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PMID:Possible involvement of phosphatidylinositol-specific phospholipase C related to pertussis toxin-sensitive GTP-binding proteins during adipocyte differentiation of 3T3-L1 fibroblasts: negative regulation of protein kinase C. 798 Dec 46

We studied the effect of endothelin-1 (ET-1) on the differentiation of adipocyte precursor cells obtained from human adipose tissue and cultured in a serum-free hormone-supplemented medium. ET-1 was found to inhibit in a dose-dependent manner the accumulation of lipid droplets and the expression of glycerol-3-phosphate dehydrogenase (GPDH), a marker of adipose differentiation. The half-maximal inhibitory effect was observed in the range of 8.5 x 10(-10) mol/L. Full inhibition required the continuous exposure of the cells to ET-1. The prevention of adipose conversion was not associated with a stimulation of mitogenesis. The presence of staurosporine, an inhibitor of the protein kinase C signaling pathway, completely prevented the inhibitory effect of ET-1 on adipose differentiation. Addition of ET-1 to newly developed fat cells also caused a suppression of GPDH activity without changing adipocyte morphology. Again, the magnitude of this effect was dependent on the exposure time. These findings suggest that ET-1 is a potent modulator of fat cell formation in man, which may act through activation of protein kinase C. Because of the close spatial relationship between fat cell precursors and blood vessels, ET-1 may exert its action in a paracrine manner.
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PMID:Endothelin-1 inhibits the adipose differentiation of cultured human adipocyte precursor cells. 812 7

G protein alpha subunits were compared by immunoblotting in preadipocytes and adipocytes from rat subcutaneous and epididymal adipose tissue at three steps of adipogenesis. The most striking difference concerned the Gq/11 alpha subunits whose expression decreased during preadipocyte differentiation in subcutaneous cells while it remained constant in epididymal cells. The PKC inhibitor CGP 41251 increased glycerol 3-phosphate dehydrogenase activity (EC 1.1.1.8), a late marker of differentiation, in epididymal preadipocytes but not in subcutaneous cells. There was no difference in the proliferation capacities between subcutaneous and epididymal preadipocytes: in both cells, CGP 41251 led to the same decrease in [(3)H]thymidine incorporation and, at confluence, the amounts of Gq/11 alpha subunits were equivalent. No major site-related difference was found in the amounts of Gs and Gi alpha during adipogenesis. Thus, compared to epididymal preadipocytes, the higher capacity of subcutaneous preadipocyte to differentiate seems to be correlated with the decrease in Gq/11 alpha expression and the decreased Gq/11 mediated PKC activation.
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PMID:Site-related differences in G-protein alpha subunit expression during adipogenesis in vitro: possible key role for Gq/11 alpha in the control of preadipocyte differentiation. 864 24

Lead exerts significant toxic effects on the nervous system, the hematopoietic system and the kidney. Specific cellular sites of action of this environmental pollutant have not been elucidated in the central nervous system. The present investigations were conducted to test the hypothesis that lead exposure perturbs glucocorticoid-mediated events in central nervous system hormonal target tissues. Utilizing the C6 glioma cell culture model in these studies, glucocorticoid receptor binding to its cytosolic receptor was investigated. Receptor binding studies yielded a Kd= 10.5 +/- 0.5 nM and a Bmax = 486 +/- 27 fmol/mg protein in untreated cells versus a Kd = 23.1 +/- 2.6 nM and Bmax = 472 +/- 35 fmol/mg protein in cells exposed to 10 microM lead acetate for 24 h. Presence of lead in these glial cells may decrease affinity of the glucocorticoid for its receptor without affecting receptor number. Treatment with 10 microM lead acetate for 48 h, resulted in a significant reduction in glucocorticoid-regulated glycerol phosphate dehydrogenase (GPDH) specific activity. These effects were not due to cell cytotoxicity assessed as cell number growth curves, [3H]thymidine incorporation or trypan blue exclusion. In protein kinase C (PKC) activity assays, treatment of cells with sodium or lead acetate and dexamethasone indicated that both lead and dexamethasone affect the distribution of PKC. In lead-treated cells cytosolic PKC activity was reduced 48% when compared to sodium acetate treated controls. Taken together, these results suggest that acute exposure of C6 cells to lead may inhibit processes involved in glucocorticoid-mediated signal transduction events within central nervous system hormonal target cells. Lead may perturb initial glucocorticoid binding events possibly by affecting PKC-mediated phosphorylations in the glucocorticoid signal transduction system.
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PMID:The acute effect of lead acetate on glucocorticoid receptor binding in C6 glioma cells. 902 May 12

Successful zygote formation during yeast mating requires cell fusion of the two haploid mating partners. To ensure that cells do not lyse as they remodel their cell wall, the fusion event is both temporally and spatially regulated: the cell wall is degraded only after cell-cell contact and only in the region of cell-cell contact. To understand how cell fusion is regulated, we identified mutants defective in cell fusion based upon their defect in mating to a fus1 fus2 strain (Chenevert, J., N. Valtz, and I. Herskowitz. 1994. Genetics 136:1287-1297). Two of these cell fusion mutants are defective in the FPS1 gene, which codes for a glycerol facilitator (Luyten, K., J. Albertyn, W.F. Skibbe, B.A. Prior, J. Ramos, J.M. Thevelein, and S. Hohmann. 1995. EMBO [Eur. Mol. Biol. Organ.] J. 14:1360-1371). To determine whether inability to maintain osmotic balance accounts for the defect in cell fusion in these mutants, we analyzed the behavior of an fps1Delta mutant with reduced intracellular glycerol levels because of a defect in the glycerol-3-phosphate dehydrogenase (GPD1) gene (Albertyn, J., S. Hohmann, J.M. Thevelein, and B.A. Prior. 1994. Mol. Cell. Biol. 14:4135-4144): deletion of GPD1 partially suppressed the cell fusion defect of fps1 mutants. In contrast, overexpression of GPD1 exacerbated the defect. The fusion defect could also be partially suppressed by 1 M sorbitol. These observations indicate that the fusion defect of fps1 mutants results from inability to regulate osmotic balance and provide evidence that the osmotic state of the cell can regulate fusion. We have also observed that mutants expressing hyperactive protein kinase C exhibit a cell fusion defect similar to that of fps1 mutants. We propose that Pkc1p regulates cell fusion in response to osmotic disequilibrium. Unlike fps1 mutants, fus1 and fus2 mutants are not influenced by expression of GPD1 or by 1 M sorbitol. Their fusion defect is thus unlikely to result from altered osmotic balance.
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PMID:Osmotic balance regulates cell fusion during mating in Saccharomyces cerevisiae. 928 76


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