Resveratrol blocks Akt activation in angiotensin II- or EGF-stimulated vascular smooth muscle cells in a redox-independent manner

Autor: Cornelia E. Schreiner, Elke H. Heiss, Verena M. Dirsch, Mario Kumerz, Atanas G. Atanasov, Julia Gesslbauer, Thomas Erker, Helge Joa, Daniel Schachner
Rok vydání: 2010
Předmět:
Male
Time Factors
Vascular smooth muscle
Physiology
030204 cardiovascular system & hematology
Antioxidants
Muscle
Smooth
Vascular
Rats
Sprague-Dawley
0302 clinical medicine
Stilbenes
NADH
NADPH Oxidoreductases
Phosphorylation
Cells
Cultured
0303 health sciences
NADPH oxidase
Angiotensin II
NOX4
Cell biology
NADPH Oxidase 4
NOX1
NADPH Oxidase 1
cardiovascular system
RNA Interference
Signal transduction
Cardiology and Cardiovascular Medicine
Oxidation-Reduction
hormones
hormone substitutes
and hormone antagonists
Signal Transduction
medicine.medical_specialty
Myocytes
Smooth Muscle
Biology
Transfection
03 medical and health sciences
Physiology (medical)
Internal medicine
Vascular smooth muscle cells
medicine
Animals
Cell Shape
Protein kinase B
030304 developmental biology
Analysis of Variance
Epidermal Growth Factor
NADPH Oxidases
Original Articles
Hydrogen Peroxide
Redox-regulation
Rats
Enzyme Activation
Endocrinology
Resveratrol
biology.protein
Proto-Oncogene Proteins c-akt
Zdroj: Cardiovascular Research
ISSN: 1755-3245
0008-6363
DOI: 10.1093/cvr/cvq355
Popis: Aims Resveratrol (RV), an antioxidant, inhibits angiotensin II (Ang II)-induced hypertrophy and Ang II- or epidermal growth factor (EGF)-induced Akt phosphorylation in rat vascular smooth muscle cells (VSMCs). Both signalling pathways are reported to utilize reactive oxygen species (ROS). The aim of this study was to show whether RV reduces the ROS level in Ang II- or EGF-activated VSMCs and whether reduction of ROS causes the impeded signalling towards Akt in the presence of RV. Methods and results We show here that RV reduces intracellular ROS and extracellular H2O2 release from VSMCs as measured using 2′,7′-dichlorodihydrofluorescein-diacetate and Amplex Red™. Since NADPH oxidases (Nox) 1 and 4 are major ROS sources in VSMCs, we examined their need for Akt phosphorylation in response to Ang II or EGF. Experiments using the blocking peptide gp91ds-tat verified a role for Nox1 in Ang II signalling towards Akt, but excluded a role for Nox1 in the respective EGF signalling. A small interfering RNA-mediated knock-down of Nox4 showed that Nox4 was not required for Ang II- or EGF-induced Akt phosphorylation. Use of the flavoprotein inhibitor diphenyleneiodonium, N -acetyl-cysteine, and non-antioxidant RV derivatives revealed that the antioxidant capacity of RV is not required for the inhibition of Akt phosphorylation, in both rat and human VSMCs. Conclusion Thus, although RV acts as an antioxidant, the antihypertrophic response of RV in VSMCs and the signalling downstream of the EGF receptor towards Akt seem to be largely redox independent.
Databáze: OpenAIRE
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