Troglitazone up-regulates vascular endothelial argininosuccinate synthase

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 t...

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Bibliographic Details
Published in:Biochemical and biophysical research communications 2008-05, Vol.370 (2), p.254-258
Main Authors: Goodwin, Bonnie L., Corbin, Karen D., Pendleton, Laura C., Levy, Monique M., Solomonson, Larry P., Eichler, Duane C.
Format: Article
Language:English
Subjects:
Animals
Argininosuccinate synthase
Argininosuccinate Synthase - genetics
Argininosuccinate Synthase - metabolism
Base Sequence
Cattle
Cell Line
Chromans - pharmacology
Citrulline–nitric oxide cycle
Endothelium, Vascular - drug effects
Endothelium, Vascular - enzymology
Gene Expression Regulation - drug effects
Ligands
Nitric oxide
Nitric Oxide - metabolism
PPAR gamma - agonists
PPAR gamma - metabolism
Response Elements - drug effects
Thiazolidinediones - pharmacology
Transcription, Genetic - drug effects
Troglitazone
Up-Regulation
Vascular endothelial cells
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Summary: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 PPARγ 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.
ISSN:0006-291X
1090-2104
DOI:10.1016/j.bbrc.2008.03.089