Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.4.3 (phospholipase C)
 18,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The present studies were carried out to investigate the effect of several growth factors on human endometrial stromal cells. In human endometrial stromal cells, bombesin and bradykinin provoked an increase in intracellular free Ca2+ and in labelled inositol phosphates when pre-incubated with [3H]myoinositol. Some or possibly all of the initial increase in intracellular free Ca2+ represented a mobilization of Ca2+ from intracellular stores and the second phase of the response depended on Ca2+ influx from the extracellular medium. [3H]Thymidine was added to human cultured endometrial stromal cells with bombesin, bradykinin, epidermal growth factor (EGF), prostaglandin F2 alpha, vasopressin and platelet-derived growth factor. Bombesin, bradykinin and EGF stimulated the incorporation of [3H]thymidine into DNA in quiescent cells. In conclusion, bombesin and bradykinin are growth factors which activate phospholipase C in human endometrial stromal cells, while EGF stimulates DNA synthesis without the activation of phospholipase C.
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PMID:Bombesin and bradykinin increase inositol phosphates and cytosolic free Ca2+, and stimulate DNA synthesis in human endometrial stromal cells. 174 75

PGJ2 and delta 12PGJ2 (1 microM to 30 microM) inhibited the growth of human astrocytoma cells (1321N1) in a time-dependent manner within 48 hrs, determined by [3H]thymidine incorporation into acid-insoluble fraction or amounts of protein. The EC50 values for PGJ2 and delta 12PGJ2 were approximately 8 microM and 6 microM, respectively. [3H]Thymidine incorporation to acid insoluble fraction was inhibited by these PGs within 1 hr, indicating that these PGs rapidly affect cell functions. Although it has been reported that an increase in cyclic AMP inhibits cell growth, PGJ2 and delta 12PGJ2, but not PGE1, reduced isoproterenol (10 microM)-induced accumulation of cyclic AMP, suggesting that PGJ2 and delta 12PGJ2 may disturb adenylate cyclase system, which might be independent on cell growth. On the other hand, these PGs inhibited the incorporation of [3H]inositol into phospholipid fraction within 6 hrs. Furthermore, PGJ2 and delta 12PGJ2 inhibited carbachol- and/or histamine-induced accumulation of inositol phosphates with a similar dose-dependency to their inhibitions of cell growth. In membrane preparations, however, PGJ2 and delta 12PGJ2 failed to inhibit GTP gamma S (10 microM)- nor Ca2+ (1 mM)-induced accumulation of inositol phosphates. The site of PGJ2 or delta 12PGJ2 in inhibition of inositol phosphate accumulation would not be phospholipase C nor a putative GTP binding protein involved in activation of phospholipase C. The present results indicate that PGJ2 and delta 12PGJ2 inhibit cell growth in human astrocytoma cells and the inhibition of phosphoinositide turnover by these PGs might be involved in the inhibition of cell growth.
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PMID:PGJ2 and delta 12PGJ2 inhibit cell growth accompanied with inhibition of phosphoinositide turnover in human astrocytoma cells. 217 1

Cultured astrocytes express bradykinin (BK) receptors, which are coupled to phospholipase C (PLC) through G-protein to mediate phosphoinositide (PI) hydrolysis. The regulation of this BK receptor-G protein-PLC pathway by cAMP and endothelin-1 (ET-1) was explored by short-term (20 min) and long-term (24 h) treatment with 100 mu M dibutyryl cyclic AMP (dBcAMP) or 10 nM ET-1. Short-term treatment of cells with dBcAMP had no effect on BK-induced PI hydrolysis; however, long-term treatment resulted in potentiation of the BK response. Similar effects were seen after 10 mu M forskolin pretreatment of the cells. We further explored the site of action of 24 h dBcAMP pretreatment and found that AlF(4)-, ionomycin- or A3187-induced PI hydrolysis was not affected but (3H)BK binding was increased. These results indicate that the site of action of dBcAMP is the BK receptor and Scatchard plot analysis showed that the Bmax was increased but the Kd decreased. Cycloheximide (0.5 mu M) blocked the increase in (3H)BK binding, indicating that new synthesis of receptor protein might occur during 24 h pretreatment with dBcAMP. Twenty minutes pretreatment of cells with ET-1 resulted in desensitization of the ET-1 induced P1 response, while the BK response was unaffected. After 24 h pretreatment with ET-1, desensitization to ET-1 still occurred, while BK-induced PI hydrolysis was markedly potentiated. (3H)BK binding and AlF(4)--induced but not A23187- or ionomycin-induced PI hydrolysis were increased, indicating that the site of action of long-term ET-1 treatment was the BK receptor and G protein; Scatchard analysis showed an increase in Bmax but no effect on Kd. These effects were blocked by cycloheximide, indicating that new synthesis of both receptor protein and G protein might occur during 24 h pretreatment with ET-1. (3H)Thymidine uptake was inhibited or potentiated by dBcAMP and ET-1, respectively. Possible dBcAMP-induced differentiation and ET-1-induced proliferation may contribute to the increased expression of receptor proteins.
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PMID:Potentiation of bradykinin-induced inositol phosphates production by cyclic AMP elevating agents and endothelin-1 in cultured astrocytes. 883 91

We examined the mechanism of action of lysophosphatidylcholine (lyso-PC), which is suggested to be involved in the pathogenesis of atherosclerosis and inflamatory disorders, and its interaction with well-known vasoactive compounds such as hydrogen peroxide (H2O2), thromboxane A2 (TX-A2), serotonin (5-HT), angiotensin II (Ang-II), endothelin-1 (ET-1), or urotensin II (U-II) on VSMC proliferation. Growth-arrested rabbit VSMCs were incubated with given concentrations of lyso-PC with H202, TX-A2, 5-HT, Ang-II, ET-1, or U-II. [3H]Thymidine incorporation into DNA was measured as an index of VSMC proliferation. Lyso-PC induced a maximal effect on [3H]thymidine incorporation at a concentration of 15 microM (156%), and its effect was significantly inhibited by the phospholipase C inhibitor U73122 (10 microM), the intracellular antioxidant NAC (400 microM), and the NADPH oxidase inhibitor diphenylene iodonium (1 microM), but not by the MAPK kinase inhibitor (10 microM). H2O2, TX-A2, 5-HT, Ang-II, ET-1, or U-II also stimulated [3H]thymidine incorporation in a dose-dependent manner. A non-mitogenic concentration of lyso-PC (5 microM) significantly potentiated the effect of low concentrations of H2O2 (0.1 microM, 110 to 222%), TX-A2 (5 microM, 120 to 202%), 5-HT (5 microM, 182 to 259%), Ang-II (0.5 microM, 167 to 304%), ET-1 (0.01 microM, 139 to 297%), or U-II (0.025 microM, 120 to 332%) on [3H]thymidine incorporation. The results suggest that lyso-PC acts synergistically with the vasoactive compounds H2O2, TX-A2, 5-HT, Ang-II, ET-1, or U-II in inducing VSMC proliferation, which may play an important role in the progression of atherosclerosis.
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PMID:Lysophosphatidylcholine potentiates the mitogenic effect of various vasoactive compounds on rabbit aortic smooth muscle cells. 1222 16

We previously reported that phospholipase C-delta1 (PLC-delta1) accumulates in the nucleus at the G1/S transition, which is largely dependent on its binding to phosphatidylinositol 4,5-bisphosphate ( Stallings, J. D., Tall, E. G., Pentyala, S., and Rebecchi, M. J. (2005) J. Biol. Chem. 280, 22060-22069 ). Here, using small interfering RNA (siRNA) that specifically targets rat PLC-delta1, we investigated whether this enzyme plays a role in cell cycle control. Inhibiting expression of PLC-delta1 significantly decreased proliferation of rat C6 glioma cells and altered S phase progression. [3H]Thymidine labeling and fluorescence-activated cell sorting analysis indicated that the rates of G1/S transition and DNA synthesis were enhanced. On the other hand, knockdown cultures released from the G1/S boundary were slower to reach full G2/M DNA content, consistent with a delay in S phase. The levels of cyclin E, a key regulator of the G1/S transition and DNA synthesis, were elevated in asynchronous cultures as well as those blocked at the G1/S boundary. Epifluorescence imaging showed that transient expression of human phospholipase C-delta1, resistant to these siRNA, suppressed expression of cyclin E at the G1/S boundary despite treatment of cultures with rat-specific siRNA. Although whole cell levels of phosphatidylinositol 4,5-bisphosphate were unchanged, suppression of PLC-delta1 led to a significant rise in the nuclear levels of this phospholipid at the G1/S boundary. These results support a role for PLC-delta1 and nuclear phospholipid metabolism in regulating cell cycle progression.
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PMID:Phospholipase C-delta1 expression is linked to proliferation, DNA synthesis, and cyclin E levels. 1835 40

It is well established that histamine modulates cell proliferation through the activation of the histamine H1 receptor (H1R), a G protein-coupled receptor (GPCR) that is known to couple to phospholipase C (PLC) activation via Gq. In the present study, we aimed to determine whether H1R activation modulates Rho GTPases, well-known effectors of Gq/G(11)-coupled receptors, and whether such modulation influences cell proliferation. Experiments were carried out in CHO cells stably expressing H1R (CHO-H1R). By using pull-down assays, we found that both histamine and a selective H1R agonist activated Rac and RhoA in a time- and dose-dependent manner without significant changes in the activation of Cdc42. Histamine response was abolished by the H1R antagonist mepyramine, RGS2 and the PLC inhibitor U73122, suggesting that Rac and RhoA activation is mediated by H1R via Gq coupling to PLC stimulation. Histamine caused a marked activation of serum response factor activity via the H1R, as determined with a serum-responsive element (SRE) luciferase reporter, and this response was inhibited by RhoA inactivation with C3 toxin. Histamine also caused a significant activation of JNK which was inhibited by expression of the Rac-GAP beta2-chimaerin. On the other hand, H1R-induced ERK1/2 activation was inhibited by U73122 but not affected by C3 or beta2-chimaerin, suggesting that ERK1/2 activation was dependent on PLC and independent of RhoA or Rac. [(3)H]-Thymidine incorporation assays showed that both histamine and the H1R agonist inhibited cell proliferation in a dose-dependent manner and that the effect was independent of RhoA but partially dependent on JNK and Rac. Our results reveal that functional coupling of the H1R to Gq-PLC leads to the activation of RhoA and Rac small GTPases and suggest distinct roles for Rho GTPases in the control of cell proliferation by histamine.
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PMID:Histamine acting on H1 receptor promotes inhibition of proliferation via PLC, RAC, and JNK-dependent pathways. 1991 13