Search results for "Phorbol 12"
showing 9 items of 9 documents
Macrophage MerTK promotes profibrogenic cross-talk with hepatic stellate cells via soluble mediators
2022
Background & aims: Activation of Kupffer cells and recruitment of monocytes are key events in fibrogenesis. These cells release soluble mediators which induce the activation of hepatic stellate cells (HSCs), the main fibrogenic cell type within the liver. Mer tyrosine kinase (MerTK) signaling regulates multiple processes in macrophages and has been implicated in the pathogenesis of non-alcoholic steatohepatitis-related fibrosis. In this study, we explored if MerTK activation in macrophages influences the profibrogenic phenotype of HSCs. Methods: Macrophages were derived from THP-1 cells or differentiated from peripheral blood monocytes towards MerTK+/CD206+/CD163+/CD209- macrophages. Th…
Inhibition of astroglial cell proliferation by alcohols: interference with the protein kinase C-phospholipase D signaling pathway.
2000
Abstract Ethanol inhibits astroglial cell proliferation, an effect that may contribute to the development of alcoholic embryopathy in humans. In the present study, we investigated inhibitory effects of ethanol and butanol isomers (1-, 2- and t -butanol) on astroglial cell proliferation induced by the strongly mitogenic phorbol ester, 4s-phorbol-12α,13s-dibutyrate (PDB). 4s-Phorbol-12α,13s-dibutyrate (PDB) induced a 10-fold increase of [3H]thymidine incorporation in cortical astrocytes prepared from newborn rats (EC 50 : 70 nM) which was blocked by Ro 31-8220, a cell-permeable protein kinase C (PKC) inhibitor. Ethanol blocked PDB-induced astroglial proliferation in a concentration-dependent …
Phospholipase D in rat myocardium: formation of lipid messengers and synergistic activation by G-protein and protein kinase C.
1998
Activation of phospholipase D (PLD) and phosphoinositide-specific phospholipase C (PI-PLC) by fluoride, to stimulate heterotrimeric G-proteins, and by phorbol esters, to stimulate protein kinase C (PKC), was studied in rat atria. Fluoride and 4beta-phorbol-12beta,13alpha-dibutyrate (PDB), in contrast to 4beta-phorbol-13alpha-acetate (PAc), activated PLD, catalyzing the formation of [3H]-phosphatidylethanol ([3H]-PETH), [3H]-phosphatidic acid ([3H]-PA), choline and sn-1,2-diacylglycerol (DAG). Basal PLD activity was resistant to drastic changes in Ca2+ and to Ro 31-8220, a PKC inhibitor, but was decreased by genistein, an inhibitor of tyrosine kinase, and increased by vanadate, a tyrosine ph…
The effects of phorbol esters on choline phospholipid hydrolysis in heart and brain
1990
The efflux of choline was determined in rat striatal slices, incubated chicken atria and perfused chicken hearts. 4 beta-Phorbol-12 beta,13 alpha-dibutyrate (PDB) and 4 beta-phorbol-12 beta-myristate, 13 alpha-acetate (PMA) were used to stimulate protein kinase C. The other phorbol esters, 4 beta-phorbol-13 alpha-acetate (PAc) and 4 alpha-phorbol-12 beta,13 alpha-didecanoate (4 alpha PDD), known to be inactive, were tested to evaluate the specificity of the responses. PDB markedly enhanced the efflux of choline in all of the three preparations. The PDB-evoked efflux of choline in incubated chicken atria was equal to the net production of choline and, therefore, was not caused by translocati…
An approach to predictive testing of contact sensitizers in vitro by monitoring their influence on endocytotic mechanisms.
1996
Endocytotic activation of epidermal Langerhans cells (LC) by immunogenic haptens is an early event during development of allergic contact dermatitis. In this work a fast and objective flow-cytometric assay for predictive in vitro testing of contact sensitizers by monitoring their influence on endocytotic mechanisms in murine LC was developed. Epidermal cell suspensions were labelled with a monoclonal antibody directed to MHC class II molecules and pH-sensitive fluorochrome-coupled second-step reagents. For untreated LC a significant quenching of fluorescence intensity by internalization of the MHC-antibody complexes into acidic compartments was noticed. Similar results were obtained in the …
Frequency-dependent effects of activation and inhibition of protein kinase C on neurohypophysial release of oxytocin and vasopressin
1989
Isolated rat neurohypophyses were superfused in vitro and the release of vasopressin and oxytocin into the medium was determined by specific radioimmunoassays. Hormone secretion was increased by electrical stimulation of the pituitary stalk at different frequencies. The effects of several phorbol esters, known to activate (phorbol 12,13-dibutyrate, PDB) or not to affect (4a-phorbol 12,13-dideconate and phorbol 12-monoacetate) protein kinase C, and of the direct protein kinase C inhibitor 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H7) were tested. Electrical stimulation with 450 pulses caused the release of about 45 μU vasopressin and 55 μU oxytocin, when a frequency of 3 Hz was applied…
Freezing without surrounding cryomedium preserves the endothelium and its function in human internal mammary arteries
2005
Abstract Purpose Cryopreserved human blood vessels may become important tools in bypass surgery. Optimal cryopreservation of an arterial graft should, therefore, preserve both histological and physiological characteristics of smooth muscle and endothelium comparable to the unfrozen artery. Methods Rings from human internal mammary arteries (IMA) were investigated in vitro either unfrozen or after immersion into a cryomedium (RPMI 1640 containing 1.8 M Me2SO and 0.1 M sucrose) and cryostorage with and without surrounding medium. Results In unfrozen IMA, neither contractile responses to noradrenaline (NA) nor endothelium-dependent relaxant responses to acetylcholine (ACH) was modified after e…
Stability of phospholipase D in primary astrocytes.
2002
Induction of expression and proteolytic breakdown of phospholipase D (PLD) isoforms in primary astrocyte cultures have been investigated. Astrocytes express both PLD1 and 2 and are dependent on PLD activity for cell proliferation [K. Kotter, J. Klein, J. Neurochem. 73 (1999) 2517]. Competitive RT-PCR analysis demonstrated a higher level of PLD1 mRNA than PLD2 mRNA (8.9 vs. 0.9amol/microg RNA, respectively). Treatment of astroglial cultures with the phorbol ester, 4beta-phorbol-12beta,13alpha-dibutyrate (0.1 microM), for 24-48h selectively induced PLD1b but not PLD1a or 2 expression as shown by PCR and Western blot; the effect was sensitive to Go 6976. In cells transiently permeabilized with…
Differential roles of PKCα and PKCɛ in controlling the gene expression of Nox4 in human endothelial cells
2007
NADPH oxidases are major sources of superoxide in the vascular wall. This study investigates the role of protein kinase C (PKC) in regulating gene expression of NADPH oxidases. Treatment of human umbilical vein endothelial cells (HUVEC) and HUVEC-derived EA.hy 926 endothelial cells with phorbol 12-myristate 13-acetate (PMA) or phorbol 12,13-dibutyrate led to a PKC-dependent biphasic expression of the gp91phox homolog Nox4. A downregulation of Nox4 was observed at 6 h and an upregulation at 48 h after phorbol ester treatment. The early Nox4 downregulation was associated with a reduced superoxide production, whereas the late Nox4 upregulation was accompanied by a clear enhancement of superoxi…