Tanshinone IIA Suppresses Hypoxia-induced Apoptosis in Medial Vestibular Nucleus Cells Via a Skp2/BKCa Axis

Author(s): Jing-Jing Zhu, Shu-Hui Wu, Xiang Chen, Ting-Ting Jiang, Xin-Qian Li, Jing-Min Li, Yong Yan, Xue-Jun Wu, Yu-Ying Liu, Pin Dong*

Journal Name: Current Pharmaceutical Design

Volume 26 , Issue 33 , 2020

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Background: The aim of the present study was to investigate the protective effects of Tanshinone IIA (Tan IIA) on hypoxia-induced injury in the medial vestibular nucleus (MVN) cells.

Methods: An in vitro hypoxia model was established using MVN cells exposed to hypoxia. The hypoxia-induced cell damage was confirmed by assessing cell viability, apoptosis and expression of apoptosis-associated proteins. Oxidative stress and related indicators were also measured following hypoxia modeling and Tan IIA treatment, and the genes potentially involved in the response were predicted using multiple GEO datasets.

Results: The results of the present study showed that Tan IIA significantly increased cell viability, decreased cell apoptosis and decreased the ratio of Bax/Bcl-2 in hypoxia treated cells. In addition, hypoxia treatment increased oxidative stress in MVN cells, and treatment with Tan IIA reduced the oxidative stress. The expression of SPhase Kinase Associated Protein 2 (SKP2) was upregulated in hypoxia treated cells, and Tan IIA treatment reduced the expression of SKP2. Mechanistically, SKP2 interacted with large-conductance Ca2+-activated K+ channels (BKCa), regulating its expression, and BKCa knockdown alleviated the protective effects of Tan IIA on hypoxia induced cell apoptosis.

Conclusion: The results of the present study suggested that Tan IIA had a protective effect on hypoxia-induced cell damage through its anti-apoptotic and anti-oxidative activity via an SKP2/BKCa axis. These findings suggest that Tan IIA may be a potential therapeutic for the treatment of hypoxia-induced vertigo.

Keywords: S-Phase Kinase Associated Protein 2, large-conductance Ca2+-activated K+ channels, Tanshinone IIA, medial vestibular nucleus, hypoxia, cell apoptosis.

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Year: 2020
Published on: 23 September, 2020
Page: [4185 - 4194]
Pages: 10
DOI: 10.2174/1381612826666200602144405
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