52,442 research outputs found
Signal transduction pathways of inflammatory gene expressions and therapeutic implications.
No full textIncreased protein kinase C isoform gamma in the hippocampus of pentylenetetrazol-induced chemoshocked mouse.
No full textP2Y receptor linked to phospholipase C: stimulation of Neuro 2A cells by UTP and ATP and possible regulation by PKC subtype epsilon.
No full textATP-evoked inositol phosphates formation through activation of P2U purinergic receptors in cultured astrocytes: Regulation by PKC subtypes alpha, delta and theta
No full textATP-induced arachidonic acid release in cultured astrocytes is mediated by Gi protein-coupled P2Y1 and P2Y2 receptors
No full textSignal transduction of arginine vasopressin-induced arachidonic acid release in H9c2 cardiac myoblasts: Role of Ca2+ and the protein kinase C-dependent activation of p42 mitogen-activated protein kinase.
No full textPole of the Cyclic Amp-Protein Kinase a Pathway in Lipopolysaccharide- Induced Nitric Oxide Synthase Expression in Raw 264.7 Macrophages - Involvement of Cyclooxygenase-2
No full textThe signaling pathway for lipopolysaccharide (LPS)-induced nitric oxide ( NO) release in RAW 264.7 macrophages involves the protein kinase C and p38 activation pathways (Chen, C. C ., Wang, J. K., and Lin, S. B. (1998) J. Immunol. 161, 6206- 6214; Chen, C. C., and Wang, J. K. (1999) Mel. Pharmacol. 55 , 481-488). In this study, the role of the cAMP-dependent protein kinase A (PKA) pathway was investigated. The PEA inhibitors, KT- 5720 and H8, reduced LPS-induced NO release and inducible nitric oxide synthase (iNOS) expression. The direct PHA activator, Bt(2)cAMP, caused concentration- dependent NO release and iNOS expression, as confirmed by immunofluorescence studies. The intracellular cAMP concentration did not increase until after 6 h of LPS treatment. Two cAMP-elevating agents, forskolin and cholera toxin, potentiated the LPS-induced NO release and iNOS expression. Stimulation of cells with LPS or Bt(2)cAMP for periods of 10 min to 24 h caused nuclear factor-kappa B (NF- kappa B) activation in the nuclei, as shown by detection of NF-kappa B-specific DNA-protein binding The PKA inhibitor, H 8, inhibited the NF-kappa B activation induced by 6- or 12-h treatment with LPS but not that induced after 1, 3, or 24 h . The cyclooxygenase-a (COX-2) inhibitors, NS-398 and indomethacin , attenuated LPS-induced NO release, iNOS expression, and NF-kappa B DNA- protein complex formation. LPS induced COX-2 expression in a time- dependent manner, and prostaglandin E-2 production was induced in parallel . These results suggest that 6 h of treatment with LPS increases intracellular cAMP levels via COX-2 induction and prostaglandin E-2 production, resulting in PKA activation, NF-kappa B activation, iNOS expression, and NO production
Protein Kinase C Eta Mediates Lipopolysaccharide-Induced Nitric-Oxide Synthase Expression in Primary Astrocytes
No full textThe signaling pathway involved in protein kinase C (PRC) activation and role of PKC isoforms in lipopolysaccharide ( LPS)-induced nitric oxide (NO ) release were studied in primary cerebellar astrocytes. LPS caused a dose - and time- dependent increase in NO release and inducible NO synthase ( iNOS) expression. The tyrosine kinase inhibitor, genestein, the phosphatidylcholine-phospholipase C inhibitor, D609, and the phosphatidate phosphodrolase inhibitor, propranolol, attenuated the LPS effects, whereas the PI-PLC inhibitor, U 73122, had no effect. The PKC inhibitors ( staurosporine, Po 31-8220, Go 6976, and calphostin C) also inhibited LPS- induced NO release and iNOS expression. However, long term ( 24 h) pretreatment of cells with 12-O-tetradecanoyl phorbol- 13-acetate (TPA) did not affect the LPS response. Previous results have shown that TPA- induced translocation, but not down-regulation, of PKC eta occurs in astrocytes (Chen, C. C ., and Chen, W. C. (1996) Glia 17, 63-71), suggesting possible involvement of PKC eta in LPS-mediated effects. Treatment with antisense oligonucleotides for PKC eta or delta, another isoform abundantly expressed in astrocytes, demonstrated the involvement of PKC eta, but not delta, in LPS-mediated effects. Stimulation of cells for 1 h with LPS caused activation of nuclear factor (NF)-kB in the nuclei as detected by the formation of a NF-kB-specific DNA-protein complex; this effect was inhibited by genestein, D609, propranolol, or Po 31-8220 or by PKC eta antisense oligonucleotides, but not by long term TPA treatment. These data suggest that in astrocytes, LPS might activate phosphatidylcholine-phospholipase C and phosphatidylcholine- phospholipase D through an upstream protein tyrosine kinase to induce PKC activation. Of the PKC isoforms present in these cells, only activation of PKC eta by LPS resulted in the stimulation of NF-kB-specific DNA-protein binding and then initiated the iNOS expression and NO release. This is further evidence demonstrating that different members of the PKC family within a single cell are involved in specific physiological responses
- …
