Troglitazone up-regulates vascular endothelial argininosuccinate synthase
- 作者：Bonnie L. Goodwin ; Karen D. Corbin ; Laura C. Pendleton ; Monique M. Levy ; Larry P. Solomonson ; Duane C. Eichler
- 关键词：Vascular endothelial cells ; Nitric oxide ; Argininosuccinate synthase ; Troglitazone ; Citrulline– ; nitric oxide cycle
- 刊名：Biochemical and Biophysical Research Communications
- 出版年：2008
- 期刊代码：159_0006291x
- 类别：bio
- 出版时间：30 May 2008
- 卷：370
- 期：2
- 页码：254-258
- 文件大小：212 K
摘要
Vascular endothelial nitric oxide (NO) production via the citrulline–NO cycle not only involves the regulation of endothelial nitric oxide synthase (eNOS), but also regulation of caveolar-localized endothelial argininosuccinate synthase (AS), which catalyzes the rate-limiting step of the cycle. In the present study, we demonstrated that exposure of endothelial cells to troglitazone coordinately induced AS expression and NO production. Western blot analysis demonstrated an increase in AS protein expression. This increased expression was due to transcriptional upregulation of AS mRNA, as determined by quantitative real time RT-PCR and inhibition by 1-d-ribofuranosylbenzimidazole (DRB), a transcriptional inhibitor. Reporter gene assays and EMSA analyses identified a distal PPARb3; response element (PPRE) (−2471 to −2458) that mediated the troglitazone increase in AS expression. Overall, this study defines a novel molecular mechanism through which a thiazolidinedione (TZD) like troglitazone supports endothelial function via the transcriptional up-regulation of AS expression.