Protein kinase C and cyclic AMP modulate thrombin-induced platelet-activating factor synthesis in human endothelial cells
Heller, R. ; Bussolino, F. ; Ghigo, D. ; Garbarino, G. ; Schroder, H. ; Pescarmona, G. ; Till, U. ; Bosia, A.
Amsterdam : Elsevier
Amsterdam : Elsevier
| ISSN: |
0167-4889
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|---|---|
| Keywords: |
Calcium ion ; Endothelium ; PAF synthesis ; Protein kinase C ; Thrombin ; cyclic AMP
|
| Source: |
Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
|
| Topics: |
Biology
Chemistry and Pharmacology
Medicine
Physics
|
| Type of Medium: |
Electronic Resource
|
| URL: |
| _version_ | 1798291649637384193 |
|---|---|
| autor | Heller, R. Bussolino, F. Ghigo, D. Garbarino, G. Schroder, H. Pescarmona, G. Till, U. Bosia, A. |
| autorsonst | Heller, R. Bussolino, F. Ghigo, D. Garbarino, G. Schroder, H. Pescarmona, G. Till, U. Bosia, A. |
| book_url | http://dx.doi.org/10.1016/0167-4889(91)90138-N |
| datenlieferant | nat_lic_papers |
| fussnote | Stimulation of human endothelial cells (EC) by thrombin elicits a rapid increase of intracellular free Ca^2^+ [(Ca^2^+]"i), platelet-activating factor (PAF) production and 1-O-alkyl-2-lyso-sn-glycero-3-phosphocholine (lyso-PAF):acetyl-CoA acetyltransferase (EC 2.3.1.67) activity. The treatment of EC with thrombin leads to a 90% decrease in the cytosolic protein kinase C (PKC) activity; this dramatic decline is accompanied by an increase of the enzymatic activity in the particulate fraction. The role of PKC in thrombin-mediated PAF synthesis has been assessed: (1) by the blockade of PKC activity with partially selective inhibitors (palmitoyl-carnitine, sphingosine and H-7); (2) by chronic exposure of EC to phorbol 12-myristate 13-acetate (PMA), which results in down-regulation of PKC. In both cases, a strong inhibition of thrombin-induced PAF production is observed, suggesting obligatory requirement of PKC activity for PAF synthesis. It is suggested that PKC regulates EC phospholipase A"2 (PLA"2) activity as thrombin-induced arachidonic acid (AA) release is 90% inhibited in PKC-depleted cells. Brief exposure of EC to PMA strongly inhibits thrombin-induced [Ca^2^+]"i rise, acetyltransferase activation and PAF production, suggesting that, in addition to the positive forward action, PKC provides a negative feedback control over membrane signalling pathways involved in the thrombin effect on EC. Forskolin and iloprost, two agents that increase the level of cellular cAMP in EC, are very effective in inhibiting thrombin-evoked cytosolic Ca^2^+ rise, acetyltransferase activation and PAF production; this suggests that endogenously generated prostacyclin (PGI"2) may modulate the synthesis of PAF in human endothelial cells. |
| hauptsatz | hsatz_simple |
| identnr | NLZ187700761 |
| issn | 0167-4889 |
| journal_name | Biochimica et Biophysica Acta (BBA)/Molecular Cell Research |
| materialart | 1 |
| package_name | Elsevier |
| publikationsort | Amsterdam |
| publisher | Elsevier |
| reference | 1093 (1991), S. 55-64 |
| schlagwort | Calcium ion Endothelium PAF synthesis Protein kinase C Thrombin cyclic AMP |
| search_space | articles |
| shingle_author_1 | Heller, R. Bussolino, F. Ghigo, D. Garbarino, G. Schroder, H. Pescarmona, G. Till, U. Bosia, A. |
| shingle_author_2 | Heller, R. Bussolino, F. Ghigo, D. Garbarino, G. Schroder, H. Pescarmona, G. Till, U. Bosia, A. |
| shingle_author_3 | Heller, R. Bussolino, F. Ghigo, D. Garbarino, G. Schroder, H. Pescarmona, G. Till, U. Bosia, A. |
| shingle_author_4 | Heller, R. Bussolino, F. Ghigo, D. Garbarino, G. Schroder, H. Pescarmona, G. Till, U. Bosia, A. |
| shingle_catch_all_1 | Heller, R. Bussolino, F. Ghigo, D. Garbarino, G. Schroder, H. Pescarmona, G. Till, U. Bosia, A. Protein kinase C and cyclic AMP modulate thrombin-induced platelet-activating factor synthesis in human endothelial cells Calcium ion Endothelium PAF synthesis Protein kinase C Thrombin cyclic AMP Calcium ion Endothelium PAF synthesis Protein kinase C Thrombin cyclic AMP 0167-4889 01674889 Elsevier |
| shingle_catch_all_2 | Heller, R. Bussolino, F. Ghigo, D. Garbarino, G. Schroder, H. Pescarmona, G. Till, U. Bosia, A. Protein kinase C and cyclic AMP modulate thrombin-induced platelet-activating factor synthesis in human endothelial cells Calcium ion Endothelium PAF synthesis Protein kinase C Thrombin cyclic AMP Calcium ion Endothelium PAF synthesis Protein kinase C Thrombin cyclic AMP 0167-4889 01674889 Elsevier |
| shingle_catch_all_3 | Heller, R. Bussolino, F. Ghigo, D. Garbarino, G. Schroder, H. Pescarmona, G. Till, U. Bosia, A. Protein kinase C and cyclic AMP modulate thrombin-induced platelet-activating factor synthesis in human endothelial cells Calcium ion Endothelium PAF synthesis Protein kinase C Thrombin cyclic AMP Calcium ion Endothelium PAF synthesis Protein kinase C Thrombin cyclic AMP 0167-4889 01674889 Elsevier |
| shingle_catch_all_4 | Heller, R. Bussolino, F. Ghigo, D. Garbarino, G. Schroder, H. Pescarmona, G. Till, U. Bosia, A. Protein kinase C and cyclic AMP modulate thrombin-induced platelet-activating factor synthesis in human endothelial cells Calcium ion Endothelium PAF synthesis Protein kinase C Thrombin cyclic AMP Calcium ion Endothelium PAF synthesis Protein kinase C Thrombin cyclic AMP 0167-4889 01674889 Elsevier |
| shingle_title_1 | Protein kinase C and cyclic AMP modulate thrombin-induced platelet-activating factor synthesis in human endothelial cells |
| shingle_title_2 | Protein kinase C and cyclic AMP modulate thrombin-induced platelet-activating factor synthesis in human endothelial cells |
| shingle_title_3 | Protein kinase C and cyclic AMP modulate thrombin-induced platelet-activating factor synthesis in human endothelial cells |
| shingle_title_4 | Protein kinase C and cyclic AMP modulate thrombin-induced platelet-activating factor synthesis in human endothelial cells |
| sigel_instance_filter | dkfz geomar wilbert ipn albert fhp |
| source_archive | Elsevier Journal Backfiles on ScienceDirect 1907 - 2002 |
| timestamp | 2024-05-06T08:35:59.608Z |
| titel | Protein kinase C and cyclic AMP modulate thrombin-induced platelet-activating factor synthesis in human endothelial cells |
| titel_suche | Protein kinase C and cyclic AMP modulate thrombin-induced platelet-activating factor synthesis in human endothelial cells Stimulation of human endothelial cells (EC) by thrombin elicits a rapid increase of intracellular free Ca^2^+ [(Ca^2^+]"i), platelet-activating factor (PAF) production and 1-O-alkyl-2-lyso-sn-glycero-3-phosphocholine (lyso-PAF):acetyl-CoA acetyltransferase (EC 2.3.1.67) activity. The treatment of EC with thrombin leads to a 90% decrease in the cytosolic protein kinase C (PKC) activity; this dramatic decline is accompanied by an increase of the enzymatic activity in the particulate fraction. The role of PKC in thrombin-mediated PAF synthesis has been assessed: (1) by the blockade of PKC activity with partially selective inhibitors (palmitoyl-carnitine, sphingosine and H-7); (2) by chronic exposure of EC to phorbol 12-myristate 13-acetate (PMA), which results in down-regulation of PKC. In both cases, a strong inhibition of thrombin-induced PAF production is observed, suggesting obligatory requirement of PKC activity for PAF synthesis. It is suggested that PKC regulates EC phospholipase A"2 (PLA"2) activity as thrombin-induced arachidonic acid (AA) release is 90% inhibited in PKC-depleted cells. Brief exposure of EC to PMA strongly inhibits thrombin-induced [Ca^2^+]"i rise, acetyltransferase activation and PAF production, suggesting that, in addition to the positive forward action, PKC provides a negative feedback control over membrane signalling pathways involved in the thrombin effect on EC. Forskolin and iloprost, two agents that increase the level of cellular cAMP in EC, are very effective in inhibiting thrombin-evoked cytosolic Ca^2^+ rise, acetyltransferase activation and PAF production; this suggests that endogenously generated prostacyclin (PGI"2) may modulate the synthesis of PAF in human endothelial cells. |
| topic | W V WW-YZ U |
| uid | nat_lic_papers_NLZ187700761 |