UMLS:C0043167 - FACTA Search

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Query: UMLS:C0043167 (pertussis)
19,595 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. The mitogen-activated protein (MAP) kinase signalling pathway can be activated by a variety of heterotrimeric Gi/Go protein-coupled and Gq/G11 protein-coupled receptors. The aims of the current study were: (i) to investigate whether the Gi/Go protein-coupled adenosine A1 receptor activates the MAP kinase pathway in transfected Chinese hamster ovary cells (CHO-A1) and (ii) to determine whether adenosine A1 receptor activation would modulate the MAP kinase response elicited by the endogenous P2Y2 purinoceptor. 2. The selective adenosine A1 receptor agonist N6-cyclopentyladenosine (CPA) stimulated time and concentration-dependent increases in MAP kinase activity in CHO-A1 cells (EC50 7.1+/-0.4 nM). CPA-mediated increases in MAP kinase activity were blocked by PD 98059 (50 microM; 89+/-4% inhibition), an inhibitor of MAP kinase kinase 1 (MEKI) activation, and by pre-treating cells with pertussis toxin (to block Gi/Go-dependent pathways). 3. Adenosine A1 receptor-mediated activation of MAP kinase was abolished by pre-treatment with the protein tyrosine inhibitor, genistein (100 microM; 6+/-10% of control). In contrast, daidzein (100 microM), the inactive analogue of genistein had no significant effect (96+/-12 of control). MAP kinase responses to CPA (1 microM) were also sensitive to the phosphatidylinositol 3-kinase inhibitors wortmannin (100 nM; 55+/-8% inhibition) and LY 294002 (30 microM; 40+/-5% inhibition) but not to the protein kinase C (PKC) inhibitor Ro 31-8220 (10 microM). 4. Activation of the endogenous P2Y2 purinoceptor with UTP also stimulated time and concentration-dependent increases in MAP kinase activity in CHO-A1 cells (EC50=1.6+/-0.3 microM). The MAP kinase response to UTP was partially blocked by pertussis toxin (67+/-3% inhibition) and by the PKC inhibitor Ro 31-8220 (10 microm; 45+/-5% inhibition), indicating the possible involvement of both Gi/Go protein and Gq protein-dependent pathways in the overall response to UTP. 5. CPA and UTP stimulated concentration-dependent increases in the phosphorylation state of the 42 kDa and 44 kDa forms of MAP kinase as demonstrated by Western blotting. 6. Co-activation of CHO-A1 cells with CPA (10 nM) and UTP (1 microM) produced synergistic increases in MAP kinase activity which were not blocked by the PKC inhibitor Ro 31-8220 (10 microM). 7. Adenosine A1 and P2Y2 purinoceptor activation increased the expression of luciferase in CHO cells transfected with a luciferase reporter gene containing the c-fos promoter. However, co-activating these two receptors produced only additive increases in luciferase expression. 8. In conclusion, our studies have shown that the transfected adenosine A1 receptor and the endogenous P2Y2 purinoceptor couple to the MAP kinase signalling pathway in CHO-A1 cells. Furthermore, co-stimulation of the adenosine A1 receptor and the P2Y2 purinoceptor produced synergistic increases in MAP kinase activity but not c-fos mediated luciferase expression.
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PMID:Human adenosine A1 receptor and P2Y2-purinoceptor-mediated activation of the mitogen-activated protein kinase cascade in transfected CHO cells. 972 63

Many of the biological effects of interleukin-8 (IL-8) are realized by binding to the two seven-transmembrane receptors IL-8 R1 and IL-8 R2. IL-8 R1 is activated only by IL-8, while IL-8 R2 is activated by IL-8, GROalpha, and a few other alpha chemokines. In addition to the well-known chemoattractant function, IL-8 is also angiogenic and mitogenic. IL-8 R1 and R2 have been shown to interact with Galphai2 and Galpha16, resulting in the activation of several mitogen-activated protein kinases. We have investigated IL-8 R1 and IL-8 R2 regulated upstream mediators and downstream effects of extracellularly responsive kinase (ERK) signaling pathways by expressing the individual receptors in a heterologous system. Our results demonstrate the following in CHO cells stably expressing either IL-8 R1 or R2 receptors: (a) IL-8 activates ERK and ERK kinases (MEK) through R1. Both IL-8 and GROalpha activate ERK and MEK through R2, whereas MIP-1alpha, a beta chemokine, does not activate these kinases through either of these receptors. (b) ERK activation is inhibited by pertussis toxin and MEK1 inhibitor. (c) ERK activation is independent of the upstream mediators Ras and Raf-1. (d) The downstream effects of ERK activation result in an increase of c-fos mRNA through both R1 and R2 receptors.
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PMID:Interleukin-8 receptors R1 and R2 activate mitogen-activated protein kinases and induce c-fos, independent of Ras and Raf-1 in Chinese hamster ovary cells. 984 97

In C9 (Clone 9) liver cells, angiotensin 11 increased the intracellular Ca2+ content, inositol phosphate production and c-fos mRNA expression. Other angiotensins were also active with the order of potency being angiotensin II = angiotensin III >> angiotensin I > angiotensin IV. Losartan, but not PD 123177 (1-(4-amino-3-methyl)-5-diphenylacetyl-4,5,6,7-tetrahydro-1H-imida zo [4,5c]pyridine-6-carboxylic acid), blocked the effects of angiotensin II. Pertussis toxin did not alter these actions of angiotensin II. These data indicate that the effects were mediated through angiotensin AT1 receptors involving pertussis toxin-insensitive G-proteins. Phorbol myristate acetate was also able to increase c-fos mRNA expression. The action of angiotensin II was consistently greater than that of the active phorbol ester. Staurosporine but not genistein inhibited this effect of angiotensin II. Angiotensin II- and phorbol myristate acetate-induced proto-oncogene mRNA expression was attenuated in cells incubated overnight with the active phorbol ester, which suggests a major role of protein kinase C.
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PMID:Angiotensin AT1 receptors in Clone 9 rat liver cells: Ca2+ signaling and c-fos expression. 987 76

Oligodendroglial cells express ionotropic glutamate receptors of alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid hydrobromide (AMPA) and kainate (KA) subtypes. Recently, we reported that AMPA receptor agonists increased 45Ca2+ uptake and phospholipase C (PLC) activity. To further elucidate the intracellular signaling mechanisms, we examined the effects of AMPA and KA on mitogen-activated protein kinase (MAPK). KA caused a time- and concentration-dependent increase in MAPK activity (predominantly the p42mapk or ERK2) and the effect was blocked by 6-cyano-7-nitro-quinoxaline-2,3-dione (CNQX), a competitive AMPA/KA receptor antagonist. Furthermore, the noncompetitive antagonists of AMPA receptor GYKI 52466 and LY 303070 prevented the actions of the agonists, indicating that the effect of KA on MAPK activation is mediated through AMPA receptors in oligodendrocyte progenitors. Chelation of extracellular Ca2+ by EDTA or inhibition of PLC with U73122 abolished MAPK activation by KA. In addition, KA-stimulated MAPK activation was reduced by the protein kinase C (PKC) inhibitors, H7 and bisindolylmaleimide, as well as downregulation of PKC by prolonged exposure to phorbol esters. The involvement of PKC in the signal transduction pathways was further supported by the ability of KA to induce translocation of PKC measured by [3H]PDBu binding. Interestingly, a wortmannin-sensitive phosphatidylinositol 3-kinase and a pertussis toxin (PTX)-sensitive G protein form part of the molecular pathways mediating MAPK activation by AMPA receptor. A specific inhibitor of MAPK kinase, PD 098059, blocked MAPK activation and reduced KA-induced c-fos gene expression. All together, these results indicate that MAPK is implicated in the transmission of AMPA signaling to the nucleus and requires extracellular Ca2+, and PLC/PKC activation.
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PMID:Molecular pathways mediating activation by kainate of mitogen-activated protein kinase in oligodendrocyte progenitors. 1009 77

Delta opioid receptors (DOR) are G-protein coupled 7-transmembrane receptors (GPCR), expressed by thymic and splenic T cells, that modulate interleukin (IL)-2 production and proliferation in response to concanavalin A or crosslinking the TCR. Mitogen-activated protein kinases (MAPKs) are involved in mediating intracellular responses to TCR crosslinking. In addition, MAPKs can be activated by signaling cascades that are initiated by the release of G-proteins from GPCRs. To determine whether DORs expressed by T cells signal through the MAPKs, extracellular-regulated kinases (ERKs) 1 and 2, two delta opioid peptides, deltorphin and [D-Ala2,D-Leu5]-enkephalin (DADLE), were studied in Jurkat cells that had been stably transfected with DOR (DOR-Ju.1). These peptides rapidly and dose-dependently induced ERK phosphorylation; pretreatment with naltrindole (NTI), a selective DOR antagonist, abolished this. Pertussis toxin (PTX) also inhibited phosphorylation, indicating the involvement of the Gi/o proteins. Herbimycin A, a protein tyrosine kinase (PTK) inhibitor, reduced the DADLE-induced ERK phosphorylation by 68%. ERK phosphorylation was inhibited by Bisindolylmaleimide 1 (GF109203X), an inhibitor of PKC, and by pretreatment with PMA prior to DADLE. A GTP/GDP exchange assay was used to assess the potential role of Ras in the pathway leading to ERK phosphorylation; DADLE failed to stimulate GTP/GDP exchange in comparison to PMA. Additional studies showed that DADLE stimulated an increase in cfos mRNA; this was reduced by the inhibitor of MAPK/ERK kinase (MEK), PD98059. Therefore, in DOR-Ju.1 cells, DOR agonists stimulate ERK phosphorylation in a Ras independent and PKC-dependent manner; PTKs appear to be involved. MAPKs mediate the increase in cfos mRNA induced by DOR agonists.
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PMID:Delta opioid receptors expressed by stably transfected jurkat cells signal through the map kinase pathway in a ras-independent manner. 1037 35

We recently demonstrated that the mitogenic effect of LDL (100 microg/mL) as well as its early intracellular signaling pathway are mediated by a pertussis-toxin (PTX)-sensitive G(i) protein-coupled receptor that is independent from its classical receptor and involves activation of extracellular response kinases (ERK1/2) (also known as p44(mapk)/p42(mapk)). In the present study we examined whether LDL-adherent factors may be responsible for some of the effects of LDL. The term "signaling activity" is used to characterize fractions that cause an increase in intracellular free Ca(2+) concentration or stimulate ERK1/2 and c-fos mRNA expression. LDL, HDL, and VLDL stimulate ERK1/2 with the following order of potency: LDL>HDL>VLDL. After delipidation of LDL with chloroform/methanol/water mixtures a PTX-sensitive signaling activity was found in one fraction arbitrarily called LDL-F. After further analysis of LDL-F compounds by high pressure liquid chromatography, a PTX-sensitive signaling activity was detected only in the fraction with a retention time of 33 minutes (arbitrarily called LDL-F33). Similarly, after separation of sphingosine-1-phosphate (SPP) and sphingosylphosphorylcholine (SPC) by high pressure liquid chromatography, a PTX-sensitive signaling activity was found in the fractions 33 and 33 to 35, respectively. These findings demonstrate that the effects of LDL-F33 are mimicked by similar fractions collected from SPP/SPC, hence suggesting that these LDL-adherent molecules are possibly closely related to SPP/SPC. A PTX-sensitive signaling activity was also detected in HDL and HDL-F33. Therefore, LDL and other lipoproteins may function as carriers for bioactive phospholipids thereby contributing to the development of coronary artery disease. Our findings support a new research concept that may contribute in elucidating cellular mechanisms promoting coronary artery disease.
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PMID:Evidence that lipoproteins are carriers of bioactive factors. 1052 71

In examining the signaling transduction pathway of adrenoceptors in oligodendrocyte progenitors, we have found that stimulation of alpha(1)-adrenoceptors with norepinephrine (NE), in the presence of 3 microM propranolol, increased the activity of mitogen-activated protein kinases (MAPKs). This stimulation was concentration- and time-dependent, with maximal response after 10 min of exposure to 10 microM NE. Pertussis toxin (PTX) blocked NE-mediated MAPK activation, suggesting that alpha(1)-adrenoceptor activates MAPK through a PTX-sensitive G-protein. In the presence of U73122, an inhibitor of phospholipase C (PLC), MAPK activation was blocked. In oligodendrocyte progenitor cultures, chronic treatment with phorbol-12-myristate-13-acetate (PMA) down-regulated protein kinase C (PKC) and blocked NE-mediated MAPK activation. The response to NE was also significantly decreased by the PKC inhibitors H7 and bisindolylmaleimide GF109203X. Similarly, the effect of NE on MAPK activation was not observed in a calcium-free medium. Furthermore, attenuation of MAPK activity was observed when cultures were pretreated with LY294002 and wortmannin, inhibitors of phosphatidylinositol-3 kinase (PI3K). These results suggest that alpha(1)-adrenoceptor-mediated activation of MAPK involves a PTX-sensitive G-protein, PLC, PI3K, and 1,2-diacyl glycerol (DAG)-dependent PKC isozyme. Stimulation of oligodendrocyte progenitors with NE also resulted in an increase in c-fos expression, which was mediated by both alpha(1)- and beta-adrenoceptor and was calcium-, PKC-, and protein kinase A (PKA)-dependent. Interestingly, in the presence of PD 098059, a specific inhibitor of MAPK kinase (MEK), both MAPK activity and c-fos expression were blocked. This suggests that MAPK is implicated in the transmission of the signal from alpha(1)-adrenoceptor to c-fos gene expression.
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PMID:Characterization of the signal transduction pathways mediating noradrenaline-stimulated MAPK activation and c-fos expression in oligodendrocyte progenitors. 1058 8

Sphingosine 1-phosphate (S1P) regulates cell proliferation, apoptosis, motility, and neurite retraction. Contradictory reports propose that S1P acts as either an intracellular second messenger or an extracellular ligand for cell-surface receptors. Hence, the precise signaling mechanisms mediating the diverse cellular effects of S1P remain to be determined. Here, we investigate whether S1P stimulation of cell proliferation, survival, and related signaling events can be mediated by the recently cloned Edg family members of G protein-coupled receptors. We observed that S1P treatment significantly increased proliferation of HTC4 hepatoma cells stably transfected with human S1P receptor Edg3 or Edg5, which was attributable to stimulation of cell growth and inhibition of apoptosis caused by serum starvation. Edg3 and Edg5 transduced S1P-evoked signaling events relevant to cell proliferation and survival, including activation of the ERK/MAP kinases, and immediate-early induction of c-Jun and c-Fos. Trancriptional activation of reporter genes for the c-fos promoter and the serum response element by Edg3 and Edg5 transfected in Jurkat cells was inhibited by pertussis toxin and C3 exoenzyme, implicating G(i/o)- and Rho-dependent pathways. Our data also indicated that Edg3 and Edg5 mediated the serum response element activation through transcriptional factors Elk-1 and serum response factor. Thus, specific G protein-coupled receptors Edg3 and Edg5 account for, at least in part, S1P-induced cell proliferation, survival, and related signaling events.
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PMID:Sphingosine 1-phosphate-induced cell proliferation, survival, and related signaling events mediated by G protein-coupled receptors Edg3 and Edg5. 1061 17

Mastoparan, a widely used tetradecapeptide activator of Gi/Go G proteins, has been reported to be a potent co-mitogen for Swiss 3T3 fibroblasts. However, we have previously shown that the peptide promotes the release of lactate dehydrogenase from Swiss 3T3 cells and evokes only a modest and delayed increase in DNA. We suggested that the ability of the peptide to permeabilise these cells may account for its mitogenic action. Here we show that mastoparan caused a rapid release of fluorescein from cells which had been pre-incubated with fluorescein diacetate, indicating that the peptide increases membrane permeability to small molecules. Furthermore, the release of lactate dehydrogenase evoked by mastoparan was lost after prolonged (24 h) incubation of cells with the peptide. Together, these data indicate that mastoparan-induced cell permeabilisation is both rapid and transient. We have also shown that mastoparan increased c-fos mRNA accumulation and that this response was not influenced by pertussis toxin or indomethacin. Although mastoparan increased the intracellular calcium concentration, the removal of extracellular calcium had no effect on mastoparan stimulated c-fos mRNA accumulation. These data show that mastoparan-induced c-fos mRNA accumulation is not mediated by activation of a G protein and subsequent activation of phospholipase D nor by a non-selective increase in calcium influx. The data have significance for the interpretation of studies in which mastoparan is, or has been, used as an activator of Gi/Go.
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PMID:Mastoparan transiently permeabilizes Swiss 3T3 cells and induces c-fos proto-oncogene expression. Role of calcium and G protein activation. 1078 31

Cholera toxin (CTX) increased c-fos mRNA level whereas it down-regulated the c-jun mRNA level in rat C6 glioma cells. In contrast to the action of CTX, pertussis toxin (PTX) did not affect either c-fos or c-jun mRNA level. The elevated c-fos mRNA level induced by CTX was significantly inhibited by the co-treatment with dexamethasone (DEX). However, DEX did not affect CTX-induced down-regulation of c-jun mRNA level. Cycloheximide (CHX) increased c-fos and c-jun mRNA levels. CHX caused a super-induction of CTX-induced c-fos mRNA level. Our results suggest that CTX-, but not PTX-, sensitive G-proteins may play an important role for c-fos mRNA up-regulation and c-jun mRNA down-regulation. In addition, DEX appears to have a selective inhibitory action against c-fos mRNA expression regulated by CTX. Ongoing protein synthesis inhibition is required for the superinduction of c-fos, but not c-jun, mRNA induced by CTX.
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PMID:Differential effects of cholera toxin and pertussis toxin on the c-fos and c-jun mRNA expression in rat C6 glioma cells. 1090 Nov 71

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