AMPK activation by Tanshinone IIA protects neuronal cells from oxygen-glucose deprivation
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Yingfeng Weng1,*, Jixian Lin1,*, Hui Liu1,*, Hui Wu1, Zhimin Yan1 and Jing Zhao1
1Department of Neurology, Minhang Branch, Zhongshan Hospital, Fudan University, Shanghai, China
Jing Zhao, email: email@example.com
Zhimin Yan, email: firstname.lastname@example.org
Keywords: OGDR; neuroprotection; Tanshinone IIA; AMP-activated protein kinase (AMPK); Ppm1e
Received: October 27, 2017 Accepted: December 01, 2017 Published: December 17, 2017
The current study tested the potential neuroprotective function of Tanshinone IIA (ThIIA) in neuronal cells with oxygen-glucose deprivation (ODG) and re-oxygenation (OGDR). In SH-SY5Y neuronal cells and primary murine cortical neurons, ThIIA pre-treatment attenuated OGDR-induced viability reduction and apoptosis. Further, OGDR-induced mitochondrial depolarization, reactive oxygen species production, lipid peroxidation and DNA damages in neuronal cells were significantly attenuated by ThIIA. ThIIA activated AMP-activated protein kinase (AMPK) signaling, which was essential for neuroprotection against OGDR. AMPKα1 knockdown or complete knockout in SH-SY5Y cells abolished ThIIA-induced AMPK activation and neuroprotection against OGDR. Further studies found that ThIIA up-regulated microRNA-135b to downregulate the AMPK phosphatase Ppm1e. Notably, knockdown of Ppm1e by targeted shRNA or forced microRNA-135b expression also activated AMPK and protected SH-SY5Y cells from OGDR. Together, AMPK activation by ThIIA protects neuronal cells from OGDR. microRNA-135b-mediated silence of Ppm1e could be the key mechanism of AMPK activation by ThIIA.
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