Heparin down-regulates the phorbol ester-induced protein kinase C gene expression in human endothelial cells: enzyme-mediated autoregulation of protein kinase C-alpha and -delta genes.
FEBS Lett
; 449(2-3): 135-40, 1999 Apr 23.
Article
in En
| MEDLINE
| ID: mdl-10338119
ABSTRACT
Overexpression of protein kinase C-alpha and protein kinase C-delta 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-alpha and -delta 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-alpha and -delta gene expression might represent a possible mechanism by which glycosaminoglycans modulate the cell growth.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Protein Kinase C
/
Tetradecanoylphorbol Acetate
/
Heparin
/
Down-Regulation
/
Gene Expression Regulation, Enzymologic
/
Isoenzymes
Limits:
Humans
Language:
En
Journal:
FEBS Lett
Year:
1999
Document type:
Article
Affiliation country:
Italy