Induction of angiotensin I-converting enzyme transcription by a protein kinase C-dependent mechanism in human endothelial cells
| Autor: | Florent Soubrier, Monique Agrapart, M. Challah, Amalia Alonso, Eric Villard |
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| Rok vydání: | 1998 |
| Předmět: |
Transcription
Genetic Biology Peptidyl-Dipeptidase A Biochemistry Gene Expression Regulation Enzymologic chemistry.chemical_compound Renin–angiotensin system Gene expression Humans RNA Messenger Enzyme Inhibitors Molecular Biology Protein kinase C Cells Cultured Protein Kinase C DNA Primers Messenger RNA Base Sequence Kinase Activator (genetics) Angiotensin-converting enzyme Cell Biology Molecular biology chemistry Phorbol biology.protein Tetradecanoylphorbol Acetate Endothelium Vascular |
| Zdroj: | The Journal of biological chemistry. 273(39) |
| ISSN: | 0021-9258 |
| Popis: | Angiotensin I-converting enzyme (ACE) has been implicated in various cardiovascular diseases; however, little is known about the ACE gene regulation in endothelial cells. We have investigated the effect of the protein kinase C activator phorbol 12-myristate 13-acetate (PMA) on ACE activity and gene expression in human umbilical vein endothelial cells (HUVEC). Our results showed a 3- and 5-fold increase in ACE activity in the medium and in the cells, respectively, after 24-h stimulation by PMA. We also observed an increase in the cellular ACE mRNA content starting after 6 h and reaching a 10-fold increase at 24 h in response to 100 ng/ml PMA as measured by ribonuclease protection assay. This effect was mediated by an increased transcription of the ACE gene as demonstrated by nuclear run-on experiments and nearly abolished by the specific PKC inhibitor GF 109203X. Our results indicate that PMA-activated PKC strongly increases ACE mRNA level and ACE gene transcription in HUVEC, an effect associated with an increased ACE secretion. A role for early growth response factor-1 (Egr-1) as a factor regulating ACE gene expression is suggested by both the presence of an Egr-1-responsive element in the proximal portion of the ACE promoter and the kinetics of the Egr-1 mRNA increase in HUVEC treated with PMA. |
| Databáze: | OpenAIRE |
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