15-Deoxy-Δ12,14-prostaglandin J2 and Thiazolidinediones Activate the MEK/ERK Pathway through Phosphatidylinositol 3-Kinase in Vascular Smooth Muscle Cells

Kotaro Takeda, Toshihiro Ichiki, Tomotake Tokunou, Naoko Iino, Akira Takeshita

研究成果: Contribution to journalArticle査読

127 被引用数 (Scopus)

抄録

Peroxisome proliferator-activated receptor (PPAR) γ belongs to the nuclear receptor superfamily of ligand-dependent transcription factors. Recent results have shown that the ligands for nuclear receptors have rapid effects so called "nongenomic" effects, which are observed within minutes after stimulation. We examined whether 15-deoxy-Δ12,14-prostaglandin J2 (15-d-PGJ2) had rapid effects on cultured vascular smooth muscle cells. Phosphorylation of ERK and c-fos mRNA expression were determined by Western and Northern blot analyses, respectively. PPARγ agonists 15-d-PGJ2 and thiazolidinediones such as pioglitazone and troglitazone elicited rapid activation of ERK within 15 min and induced c-fos mRNA expression within 30 min, whereas the PPARα agonist bezafibrate failed to activate ERK. 15-d-PGJ2-induced expression of c-fos mRNA was blocked by PD98059 or U0126, two ERK kinase inhibitors, suggesting that the MEK/ERK pathway mediates 15-d-PGJ2-induced c-fos gene expression. Furthermore, pretreatment with wortmannin, an inhibitor of phosphatidylinositol 3 (PI3)-kinase, inhibited 15-d-PGJ2-induced ERK activation and c-fos mRNA expression, suggesting that PI3-kinase is involved in the process. An electrophoretic mobility shift assay showed that 15-d-PGJ2 enhanced AP-1 binding activity to AP-1 consensus sequence in a time-dependent manner. 15-d-PGJ2 increased thymidine incorporation in a PI3-kinase-dependent manner. Taken together, our findings show that 15-d-PGJ2 and thiazolidinediones activate the MEK/ERK pathway through PI3-kinase and lead to c-fos mRNA expression and DNA synthesis. These findings indicate a novel regulatory mechanism of gene expression by 15-d-PGJ2 and thiazolidinediones.

本文言語英語
ページ(範囲)48950-48955
ページ数6
ジャーナルJournal of Biological Chemistry
276
52
DOI
出版ステータス出版済み - 12 28 2001

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

フィンガープリント 「15-Deoxy-Δ<sup>12,14</sup>-prostaglandin J<sub>2</sub> and Thiazolidinediones Activate the MEK/ERK Pathway through Phosphatidylinositol 3-Kinase in Vascular Smooth Muscle Cells」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。

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