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Molecular and Cellular Biochemistry

, Volume 425, Issue 1–2, pp 125–138 | Cite as

Induction of autophagy by salidroside through the AMPK-mTOR pathway protects vascular endothelial cells from oxidative stress-induced apoptosis

  • Xiang-Tao Zheng
  • Zi-Heng Wu
  • Ye Wei
  • Ju-Ji Dai
  • Guan-Feng Yu
  • FengLai YuanEmail author
  • Le-Chi YeEmail author
Article

Abstract

Vascular endothelial cells are highly sensitive to oxidative stress, and this is one of the mechanisms by which widespread endothelial dysfunction is induced in most cardiovascular diseases and disorders. However, how these cells can survive in oxidative stress environments remains unclear. Salidroside, a traditional Chinese medicine, has been shown to confer vascular protective effects. We aimed to understand the role of autophagy and its regulatory mechanisms by treating human umbilical vein endothelial cells (HUVECs) with salidroside under oxidative stress. HUVECs were treated with salidroside and exposed to hydrogen peroxide (H2O2). The results indicated that salidroside exerted cytoprotective effects in an H2O2-induced HUVEC injury model and suppressed H2O2-induced apoptosis of HUVECs. Pretreatment with 3-methyladenine (3-MA), an autophagy inhibitor, increased oxidative stress-induced HUVEC apoptosis, while the autophagy activator rapamycin induced anti-apoptosis effects in HUVECs. Salidroside increased autophagy and decreased apoptosis of HUVECs in a dose-dependent manner under oxidative stress. Moreover, 3-MA attenuated salidroside-induced HUVEC autophagy and promoted apoptosis, whereas rapamycin had no additional effects compared with salidroside alone. Salidroside upregulated AMPK phosphorylation but downregulated mTOR phosphorylation under oxidative stress; however, administration of compound C, an AMPK inhibitor, abrogated AMPK phosphorylation and increased mTOR phosphorylation and apoptosis compared with salidroside alone. These results suggest that autophagy is a protective mechanism in HUVECs under oxidative stress and that salidroside might promote autophagy through activation of the AMPK pathway and downregulation of mTOR pathway.

Keywords

Autophagy Salidroside Vascular endothelial cells Oxidative stress Signaling pathway 

Notes

Acknowledgements

This work was supported by the Natural Science Foundation of China (81270011; 81472125). Zhejiang Provincial Natural Science Foundation of China under Grant (No. LY15H160058); Zhejiang Provincial Medical technology science project (No. 2015KYB245).

Compliance with ethical standards

Conflict of interest

The authors declare that this research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Supplementary material

11010_2016_2868_MOESM1_ESM.docx (399 kb)
Supplementary material 1 (DOCX 399 kb)

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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  1. 1.Department of Vascular SurgeryThe First Affiliated Hospital of Wenzhou Medical UniversityWenzhouPeople’s Republic of China
  2. 2.Department of Vascular Surgery, The First Affiliated Hospital, School of MedicineZhejiang UniversityHangzhouPeople’s Republic of China
  3. 3.Department of General Surgery, Zhongshan HospitalFudan UniversityShanghaiPeople’s Republic of China
  4. 4.Department of Central LaboratoryThe third Hospital Affiliated to Nantong UniversityWuxiPeople’s Republic of China
  5. 5.Department of Oncological SurgeryThe First Affiliated Hospital of Wenzhou Medical UniversityWenzhouPeople’s Republic of China

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