Abstract
Resveratrol (RSV), a phytoalexin, has shown to prevent endothelial dysfunction and reduce diabetic vascular complications and the risk of cardiovascular diseases. The aim of this study was to investigate the signaling mechanisms underlying the protecting effects of RSV against endothelial dysfunction during hyperglycemia in vitro and in vivo. Human umbilical vein endothelial cells (HUVECs) were treated with RSV, and then exposed to high glucose (HG, 30 mmol/L). Akt-Ser473 phosphorylation, eNOS-Ser1177 phosphorylation, and PTEN protein levels in the cells were detected using Western blot. For in vivo studies, WT and Akt−/− mice were fed a normal diet containing RSV (400 mg·kg−1·d−1) for 2 weeks, then followed by injection of STZ to induce hyperglycemia (300 mg/dL). Endothelial function was evaluated using aortic rings by assessing ACh-induced vasorelaxation. RSV (5–20 μmol/L) dose-dependently increased Akt-Ser473 phosphorylation, accompanied by increased eNOS-Ser1177 phosphorylation in HUVECs; these effects were more prominent under HG stimulation. Transfection with Akt siRNA abolished RSV-enhanced eNOS phosphorylation and NO release. Furthermore, RSV (5–20 μmol/L) dose-dependently decreased the levels of PTEN, which was significantly increased under HG stimulation, and PTEN overexpression abolished RSV-stimulated Akt phosphorylation in HG-treated HUVECs. Moreover, RSV dramatically increased 26S proteasome activity, which induced degradation of PTEN. In in vivo studies, pretreatment with RSV significantly increased Akt and eNOS phosphorylation in aortic tissues and ACh-induced vasorelaxation, and improved diabetes-induced endothelial dysfunction in wild-type mice but not in Akt−/− mice. RSV attenuates endothelial function during hyperglycemia via activating proteasome-dependent degradation of PTEN, which increases Akt phosphorylation, and consequentially upregulation of eNOS-derived NO production.
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17 January 2020
An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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Acknowledgements
This work was supported by National Natural Science Foundation of China (81260039, 81470591, 81560061, and 81570723) and the First Batch of Senior Medical Personnel Training in Guangxi “139” Plan Funding and Nature Science Foundations of China and GuangXi Province (S201303-06, 2013GXNSFAA278005).
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The Editor has retracted this article [1] because there is significant overlap of figures and text with [2].
Specifically:
• Figure 1a [1] appears to be identical with sub panels in Figures 1b and 1d [2]
• Figure 1d [1] appears to be identical with a sub-panel in Figure 1e [2]
• Figure 2a and 2b [1] appears to be identical with Figure 2a [2]
• Figures 2c, 2d, 4a, 4b and 4c in [1] appear to be identical with Figures 2c, 2d, 4a, 4b and 4c in [2]
• Figure 3a [1] appears to be identical with Figure 3b [2]
• Figure 3b [1] appears to be identical with Figure 3c [2]
• Figures 5a, 5c, 5d and 5f in [1] appear to be identical with Figures 6a, 6b, 6c and 6d in [2], respectively.
• Figure 6b [1] appears to be identical with Figure 8a [2]
The Editor therefore has no confidence in this article.
The authors have told us that all the Western blots in this article were produced by an external experimental company; this was not stated in the article. [All authors agree with this retraction]
1. Li J-y, Huang W-q, Tu R-h, Zhong G-q, Luo B-b & He Y. Resveratrol rescues hyperglycemia-induced endothelial dysfunction via activation of Akt. Acta Pharmacologica Sinica_38.2 (2017): 182.
2. Retracted article: Xu, Bing-Can, Hui-Bao Long, and Ke-Qin Luo. Tert-butylhydroquinone lowers blood pressure in AngII-induced hypertension in mice via proteasome-PTEN-Akt-eNOS pathway. Scientific Reports 6 (2016): 29589.
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Li, Jy., Huang, Wq., Tu, Rh. et al. RETRACTED ARTICLE: Resveratrol rescues hyperglycemia-induced endothelial dysfunction via activation of Akt. Acta Pharmacol Sin 38, 182–191 (2017). https://doi.org/10.1038/aps.2016.109
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DOI: https://doi.org/10.1038/aps.2016.109
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