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PI3K/Akt/uncoupling protein 2 signaling pathway may be involved in cell senescence and apoptosis induced by angiotensin II in human vascular endothelial cells

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Abstract

Oxidative DNA damage contributes to replicative senescence. We explored the mechanism by which angiotensin II (Ang II) induces senescence in human vascular endothelial cells (HUVECs). Following weeklong incubation with Ang II, cell senescence, apoptosis, reactive oxygen species (ROS) content and mitochondrial membrane potential (MMP) were measured by β-galactosidase, annexin V/propidium iodide, DCFH-DA and rhodamine 123 staining, respectively. The protein levels of telomerase reverse transcriptase (TERT), UCP2, Akt, phosphor (p)-Akt, c-myc, and p53 were assessed by immunoblot. LY294002 was applied to inhibit PI3K/Akt signaling. Ang II induced HUVEC senescence and apoptosis, and increased ROS content and depolarization of MMP in a dose-dependent manner. Ang II further elevated protein levels of TERT from 0.006 ± 0.041 at baseline, to 0.480 ± 00.031 in the presence of 10 µM Ang II, UCP2 from 0.297 ± 0.051 to 2.512 ± 0.024, p-Akt from 0.012 ± 0.024 to 0.874 ± 0.015, c-myc from 0.521 ± 0.015 to 1.064 ± 0.025, and p53 from 0.035 ± 0.047 to 1.195 ± 0.029 (all P < 0.01, vs. baseline). LY294002 pre-treatment significantly alleviated Ang II-induced HUVEC senescence, and partly reversed the elevation of TERT, UCP2, p-Akt, c-myc and p53 protein levels. PI3K/Akt/UCP2 signaling may be involved in cell senescence and apoptosis induced by Ang II in HUVECs.

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Acknowledgments

This study was supported by the National Nature Science Foundation of China (Grant 31140019), Nature Science Foundation of Jiangxi Province (Grant 20122BAB205007) and Science and Technology Support Program of Nanchang city. The authors thank Molecular Center of the Second Affiliated Hospital of Nanchang University for their help in providing the equipment and technical support.

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All authors declare that they have no conflict of interests.

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Authors and Affiliations

  1. Department of Cardiovascular, The Second Affiliated Hospital to Nanchang University, Nanchang, 330006, Jiangxi, China

    Ping Li, Xin Guo, Pingping Lei, Shoujun Shi, Shike Luo & Xiaoshu Cheng

  2. Department of Cardiology, The First Affiliated Hospital to Gannan Medical University, Ganzhou, 341000, Jiangxi, China

    Xin Guo

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  1. Ping Li
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  2. Xin Guo
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Correspondence to Ping Li.

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Ping Li and Xin Guo are the co-first authors.

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Li, P., Guo, X., Lei, P. et al. PI3K/Akt/uncoupling protein 2 signaling pathway may be involved in cell senescence and apoptosis induced by angiotensin II in human vascular endothelial cells. Mol Biol Rep 41, 6931–6937 (2014). https://doi.org/10.1007/s11033-014-3580-0

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