title: Regulation of type I plasminogen activator inhibitor synthesis by protein kinase C and cAMP in bovine aortic endothelial cells.
abstract: The second messengers and protein kinases involved in the induction of type I plasminogen activator inhibitor (PAI-1) synthesis by various agents were evaluated in cultured bovine aortic endothelial cells. Phorbol myristate acetate (PMA) induced PAI-1 in these cells implicating the protein kinase C (PK-C) pathway. However, bradykinin, which also activates PK-C in bovine aortic endothelial cells, did not induce PAI-1. Moreover, when PK-C was down-regulated by PMA pretreatment, subsequent induction of PAI-1 by transforming growth factor beta (TGF beta) and tumor necrosis factor alpha (TNF alpha) was unaltered, and induction by lipopolysaccharide (LPS) was decreased by only 50%. LPS increased phospholipid second messengers which can activate PK-C but TGF beta and TNF alpha did not. Agents which increase cAMP, (e.g., forskolin and isobutylmethylxanthine) blocked the induction of PAI-1 synthesis by PMA, LPS, TGF beta and TNF alpha suggesting that induction may occur by lowering cAMP. This possibility seems unlikely since cAMP levels did not change in response to any of these agents. Moreover, somatostatin lowered cAMP but did not induce PAI-1. PAI-1 was not induced by treating the cells with cGMP, Na+/H+ ionophore and calcium ionophore or arachidonic acid.
authors.affiliation: Committee on Vascular Biology, Research Institute of Scripps Clinic, La Jolla, CA 92037.
authors.forename: S R
authors.initials: SR
authors.lastname: Slivka
authors.forename: D J
authors.initials: DJ
authors.lastname: Loskutoff
mesh_terms: D000818:Animals; D001011:Aorta; D002417:Cattle; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000502:physiology*; D015536:Down-Regulation; D004730:Endothelium, Vascular / Q000378:metabolism; D006868:Hydrolysis; D015151:Immunoblotting; D010743:Phospholipids / Q000378:metabolism; D015849:Plasminogen Inactivators / Q000378:metabolism*; D011493:Protein Kinase C / Q000502:physiology*
chemical_list: D010743:Phospholipids; D015849:Plasminogen Inactivators; D000242:Cyclic AMP; D011493:Protein Kinase C