Open AccessEndothelin-1 Induces Cyclooxygenase-2 Expression and Generation of Reactive Oxygen Species in Endothelial Cells
Author(s) -
Toru Sugiyama,
Takanobu Yoshimoto,
Ryuji Sakakibara,
Nozomi Fukai,
Naoko Ozawa,
Masayoshi Shichiri,
Yukio Hirata
Publication year - 2004
Publication title -
journal of cardiovascular pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.762
H-Index - 100
eISSN - 1533-4023
pISSN - 0160-2446
DOI - 10.1097/01.fjc.0000166267.17174.0e
Subject(s) - downregulation and upregulation , endothelin 1 , dichlorofluorescein , protein kinase c , aldosterone , cyclooxygenase , reactive oxygen species , endocrinology , extracellular , intracellular , endothelin receptor , chemistry , medicine , biology , signal transduction , microbiology and biotechnology , pharmacology , receptor , biochemistry , enzyme , gene
Since both endothelin-1 (ET-1) and aldosterone have been shown to induce expression of several pro-inflammatory genes, including cyclooxygenase-2 (COX-2), in the vasculature as a cardiovascular risk hormone, the present study was undertaken to examine the effects of ET-1 and aldosterone on COX-2 gene expression as measured by a real-time reverse transcriptase-polymerase chain reaction in aortic endothelial cells. Treatment with ET-1(10 M) markedly upregulated COX-2 mRNA levels in rat endothelial cells, whereas aldosterone (10 M) did not show any effect. The ET-1-induced COX-2 upregulation was inhibited by pretreatment with a non-selective endothelin receptor antagonist (TAK044), a protein kinase C inhibitor (GF109203X), and a MEK inhibitor (PD98059). Furthermore, ET-1 increased intracellular reactive oxygen species generation as estimated by the measurement of dichlorofluorescein fluorescence, whose effect was blocked by a COX-2 inhibitor (NS398). Our data show that ET-1 induces COX-2 upregulation in rat endothelial cells via a protein kinase C-dependent and extracellular signal-regulated kinase-dependent pathway, which may largely contribute to the generation of intracellular reactive oxygen species.