Heparin down‐regulates the phorbol ester‐induced protein kinase C gene expression in human endothelial cells: enzyme‐mediated autoregulation of protein kinase C‐α and ‐δ genes1
- 23 April 1999
- journal article
- Published by Wiley in FEBS Letters
- Vol. 449 (2-3), 135-140
- https://doi.org/10.1016/s0014-5793(99)00438-x
Abstract
Overexpression of protein kinase C‐α and protein kinase C‐δ has been shown to modulate a number of biological effects, including the cell growth and differentiation. We hypothesized that heparin, a potent antimitogenic drug, could affect the cell proliferation by inhibiting the expression of specific protein kinase C genes. Heparin, markedly but not completely, inhibited the serum‐stimulated protein kinase C‐α and ‐δ mRNA expression. Protein kinase C inhibition or down‐regulation significantly decreased the serum‐induced protein kinase C isoenzyme gene expression. Heparin failed to inhibit the residual effect of serum that was resistant to the above‐mentioned treatments. Phorbol 12‐myristate 13‐acetate elicited an increase of protein kinase C isoenzyme gene expression that was completely prevented by protein kinase C inhibition or down‐regulation. Heparin dose‐dependently counteracted and ultimately abolished the increase in the protein kinase C isoenzyme gene expression elicited by phorbol 12‐myristate 13‐acetate. These results suggest that the inhibition of an autoregulatory role wielded by protein kinase C on the protein kinase C‐α and ‐δ gene expression might represent a possible mechanism by which glycosaminoglycans modulate the cell growth.Keywords
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