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Heparin inhibits phorbol ester‐induced ornithine decarboxylase gene expression in endothelial cells
Author(s) -
Pintus Gianfranco,
Tadolini Bruna,
Maioli Margherita,
Posadino Anna M.,
Bennardini Federico,
Bettuzzi Saverio,
Ventura Carlo
Publication year - 1998
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(98)00073-8
Subject(s) - ornithine decarboxylase , protein kinase c , dna synthesis , chelerythrine , microbiology and biotechnology , gene expression , phorbol , heparin , cell growth , biology , chemistry , biochemistry , dna , kinase , enzyme , gene
Glycosaminoglycans regulate angiogenesis by affecting the availability of different growth factors for the endothelial cell (EC). However, little is known about the molecular and functional consequences resulting from direct interaction of these polyelectrolytes with the EC. Here we show that heparin markedly inhibited serum‐stimulated DNA synthesis and ornithine decarboxylase (ODC) mRNA expression in human endothelial cells (HEC). About 50% of the serum effect on DNA synthesis and ODC gene expression was prevented by the selective protein kinase C (PKC) inhibitor chelerythrine or by PKC down‐regulation. Heparin was ineffective in counteracting that part of the effect of serum that was resistant to PKC inhibition or down‐regulation. In serum‐free cultured HEC, heparin completely abolished the increase in DNA synthesis and ODC mRNA expression elicited by a number of PKC activators. Cell exposure to difluoromethylornithine, an irreversible inhibitor of ODC enzyme, dramatically antagonised both serum‐ and phorbol 12‐myristate 13‐acetate (PMA)‐stimulated DNA synthesis. These results suggest that inhibition of PKC‐mediated ODC gene expression by glycosaminoglycans may represent an important mechanism in the regulation of HEC proliferation.