Abstract Title:

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

Abstract Source:

Cardiovasc Res. 2010 Dec 17. Epub 2010 Dec 17. PMID: 21071431

Abstract Author(s):

Cornelia E Schreiner, Mario Kumerz, Julia Gesslbauer, Daniel Schachner, Helge Joa, Thomas Erker, Atanas G Atanasov, Elke H Heiss, Verena M Dirsch

Article Affiliation:

Department of Pharmacognosy, University of Vienna, Althanstraße 14, 1090 Vienna, Austria.

Abstract:

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 H(2)O(2) 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.

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