Protein Kinase C-Mediated Inhibition of Cyclin A Expression in Human Vascular Endothelial Cells
| Autor: | Kentaro Shimokado, Katsuhiro Zen, Jun Ogata, Chiya Kosaka, Toshiyuki Sasaguri, Junichi Masuda, Tasuku Yokota |
|---|---|
| Rok vydání: | 1993 |
| Předmět: |
DNA Replication
Umbilical Veins medicine.medical_specialty Time Factors Cyclin D Blotting Western Cyclin A Biophysics Gene Expression Biochemistry Diglycerides Cyclins Internal medicine medicine Humans RNA Messenger Molecular Biology Cells Cultured Protein Kinase C Protein kinase C Cyclin Cell Nucleus biology Cell growth Cyclin-dependent kinase 2 Cell Biology Cell cycle Cell biology Endothelial stem cell Kinetics Endocrinology biology.protein Tetradecanoylphorbol Acetate Fibroblast Growth Factor 2 Endothelium Vascular |
| Zdroj: | Biochemical and Biophysical Research Communications. 193:991-998 |
| ISSN: | 0006-291X |
| Popis: | Proliferation of cultured human vascular endothelial cells may be negatively regulated by the protein kinase C (PKC) pathway, because phorbol 12-myristate, 13-acetate (PMA) inhibits DNA synthesis and cell population doubling in PKC-retaining cells, but not in cells depleted of PKC by a long-term exposure to PMA. We investigated the mechanism through which PKC arrests the cell cycle with regard to cyclin A, which has been reported to play a key role in G1/S progression activating CDK2. Cyclin A mRNA was elevated from late G1 in accordance with the protein expression, which reached the maximal level during the S phase. PMA added at late G1 potently reduced the levels of cyclin A mRNA and the protein in concentration-dependent manners parallel to its effect on the proliferation. However, it failed to inhibit the expression in PKC-depleted cells. The mRNA reduction by PMA was due to inhibition of the transcription. The PMA effects were mimicked by multiple doses of 1,2-dioctanoylglycerol. These findings suggest that PKC inhibits G1/S progression through suppression of cyclin A gene transcription in endothelial cells. |
| Databáze: | OpenAIRE |
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