Endothelin-1 Induces Cyclooxygenase-2 Expression and Generation of Reactive Oxygen Species in Endothelial Cells
2004; Lippincott Williams & Wilkins; Volume: 44; Issue: Supplement 1 Linguagem: Inglês
10.1097/01.fjc.0000166267.17174.0e
ISSN1533-4023
AutoresToru Sugiyama, Takanobu Yoshimoto, Ryuji Sato, Nozomi Fukai, Naoko Ozawa, Masayoshi Shichiri, Yukio Hirata,
Tópico(s)Hormonal Regulation and Hypertension
ResumoSince 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 transcriptasepolymerase chain reaction in aortic endothelial cells. Treatment with ET-1(10-7M) markedly upregulated COX-2 mRNA levels in rat endothelial cells, whereas aldosterone (10-7M) 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 kinasedependent pathway, which may largely contribute to the generation of intracellular reactive oxygen species.
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