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Resveratrol inhibits angiotensin II-induced endothelin-1 gene expression and subsequent proliferation in rat aortic smooth muscle cells
- Source :
- European journal of pharmacology. 515(1-3)
- Publication Year :
- 2005
-
Abstract
- Resveratrol is a phytoestrogen naturally found in grapes and is the major constituent of wine thought to have a cardioprotective effect. The aims of this study were to examine whether resveratrol alters angiotenisn II-induced cell proliferation and endothelin-1 gene expression and to identify the putative underlying signaling pathways in rat aortic smooth muscle cells. Cultured rat aortic smooth muscle cells were preincubated with resveratrol then stimulated with angiotensin II, after which [ 3 H]thymidine incorporation and endothelin-1 gene expression were examined. The intracellular mechanism of resveratrol in cellular proliferation and endothelin-1 gene expression was elucidated by examining the phosphorylation level of angiotensin II-induced extracellular signal-regulated kinase (ERK). The inhibitory effects of resveratrol (1–100 μM) on angiotensin II-induced DNA synthesis and endothelin-1 gene expression were demonstrated with Northern blot and promoter activity assays. Measurements of 2′7′-dichlorofluorescin diacetate, a redox-senstive fluorescent dye, showed a resveratrol-mediated inhibition of intracellular reactive oxygen species generated by the effects of angiotensin II. The inductive properties of angiotensin II and H 2 O 2 on ERK phosphorylation and activator protein-1-mediated reporter activity were found reversed with resveratrol and antioxidants such as N -acetyl-cysteine. In summary, we speculate that resveratrol inhibits angiotensin II-induced cell proliferation and endothelin-1 gene expression, and does so in a manner which involves the disruption of the ERK pathway via attenuation of reactive oxygen species generation. Thus, this study provides important insight into the molecular pathways that may contribute to the proposed beneficial effects of resveratrol on the cardiovascular system.
- Subjects :
- MAPK/ERK pathway
Male
Angiotensin receptor
Blotting, Western
Gene Expression
Resveratrol
Biology
Transfection
Muscle, Smooth, Vascular
Rats, Sprague-Dawley
chemistry.chemical_compound
Gene expression
Stilbenes
Animals
Northern blot
RNA, Messenger
Phosphorylation
Extracellular Signal-Regulated MAP Kinases
Luciferases
Aorta
Cells, Cultured
Cell Proliferation
Pharmacology
Binding Sites
Dose-Response Relationship, Drug
Endothelin-1
Activator (genetics)
Angiotensin II
food and beverages
Hydrogen Peroxide
Blotting, Northern
Cell biology
Rats
Transcription Factor AP-1
chemistry
Biochemistry
Signal transduction
Reactive Oxygen Species
Subjects
Details
- ISSN :
- 00142999
- Volume :
- 515
- Issue :
- 1-3
- Database :
- OpenAIRE
- Journal :
- European journal of pharmacology
- Accession number :
- edsair.doi.dedup.....96819ef3872206a560e60847fbc6dda6