{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,27]],"date-time":"2025-10-27T04:57:31Z","timestamp":1761541051153},"reference-count":0,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arterioscler Thromb"],"published-print":{"date-parts":[[1991,7]]},"abstract":"<jats:p>Activation of protein kinase C leads to a strong induction of tissue-type plasminogen activator (t-PA) expression in endothelial cells. Using endothelial cells from human umbilical vein (HUVECs) and human aorta (HAECs), we have studied this regulation of t-PA and its inhibitor, plasminogen activator inhibitor-1 (PAI-1), at the mRNA level and have compared their induction with the expression of platelet-derived growth factors A and B (PDGF-A and PDGF-B) and the proto-oncogenes c-jun and c-fos. Treatment of HUVECs with exogenous bacterial phospholipase C or the synthetic diacylglycerol 1-oleoyl-2-acetylglycerol led to a threefold and a twofold increase, respectively, in t-PA concentrations in 24-hour-conditioned medium. Similarly, the more stable protein kinase C activator 4 beta-phorbol-12-myristate-13-acetate (PMA) caused about a 10-fold increase in t-PA antigen levels. This effect of PMA is maximal between 8 and 16 hours at a concentration of 10 nM and is fully accounted for by parallel increases in t-PA mRNA levels. An increase in intracellular cyclic adenosine monophosphate levels by forskolin (10 microM) slightly diminished t-PA expression but further enhanced the PMA-induced increases in t-PA synthesis and mRNA levels by at least twofold. PMA also enhanced the mRNA levels of two other important endothelium-expressed genes, PDGF-A and PDGF-B, with a time profile similar to that of t-PA, with peak values about fivefold higher than control values. Forskolin did not further stimulate this PMA-induced PDGF expression in HUVECs, which suggests a regulatory mechanism different from that of t-PA. Qualitatively very similar induction patterns of t-PA, PDGF-A, and PDGF-B were seen with HAECs. In contrast to t-PA and PDGF, PAI-1 mRNA and antigen levels increased only slightly after PMA treatment of HUVECs or HAECs; forskolin alone or in combination with PMA diminished the expression of PAI-1. The induction of t-PA mRNA by PMA was dependent on protein synthesis and was preceded by a strong transient increase in c-jun and c-fos mRNA levels; the induction of c-fos but not of c-jun was potentiated by forskolin. Because the products of these two proto-oncogenes form dimeric complexes for which specific binding sites are present in the t-PA promoter region, they may mediate the protein kinase C-dependent increase in t-PA gene expression, including the stimulating action of cyclic adenosine monophosphate.<\/jats:p>","DOI":"10.1161\/01.atv.11.4.1042","type":"journal-article","created":{"date-parts":[[2011,6,17]],"date-time":"2011-06-17T19:44:19Z","timestamp":1308339859000},"page":"1042-1052","source":"Crossref","is-referenced-by-count":36,"title":["Role of protein kinase C and cyclic adenosine monophosphate in the regulation of tissue-type plasminogen activator, plasminogen activator inhibitor-1, and platelet-derived growth factor mRNA levels in human endothelial cells. Possible involvement of proto-oncogenes c-jun and c-fos."],"prefix":"10.1161","volume":"11","author":[{"given":"T","family":"Kooistra","sequence":"first","affiliation":[{"name":"Gaubius Laboratory IVVO-TNO, Leiden, The Netherlands."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P J","family":"Bosma","sequence":"additional","affiliation":[{"name":"Gaubius Laboratory IVVO-TNO, Leiden, The Netherlands."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K","family":"Toet","sequence":"additional","affiliation":[{"name":"Gaubius Laboratory IVVO-TNO, Leiden, The Netherlands."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"L H","family":"Cohen","sequence":"additional","affiliation":[{"name":"Gaubius Laboratory IVVO-TNO, Leiden, The Netherlands."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M","family":"Griffioen","sequence":"additional","affiliation":[{"name":"Gaubius Laboratory IVVO-TNO, Leiden, The Netherlands."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"E","family":"van den Berg","sequence":"additional","affiliation":[{"name":"Gaubius Laboratory IVVO-TNO, Leiden, The Netherlands."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"L","family":"le Clercq","sequence":"additional","affiliation":[{"name":"Gaubius Laboratory IVVO-TNO, Leiden, The Netherlands."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"V W","family":"van Hinsbergh","sequence":"additional","affiliation":[{"name":"Gaubius Laboratory IVVO-TNO, Leiden, The Netherlands."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","container-title":["Arteriosclerosis and Thrombosis: A Journal of Vascular Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/pdf\/10.1161\/01.ATV.11.4.1042","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,3,17]],"date-time":"2022-03-17T17:50:54Z","timestamp":1647539454000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/01.ATV.11.4.1042"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1991,7]]},"references-count":0,"journal-issue":{"issue":"4","published-print":{"date-parts":[[1991,7]]}},"alternative-id":["10.1161\/01.ATV.11.4.1042"],"URL":"https:\/\/doi.org\/10.1161\/01.atv.11.4.1042","relation":{},"ISSN":["1049-8834"],"issn-type":[{"value":"1049-8834","type":"print"}],"subject":[],"published":{"date-parts":[[1991,7]]}}}