AMPK activation by Tanshinone IIA protects neuronal cells from oxygen-glucose deprivation

// Yingfeng Weng 1, * , Jixian Lin 1, * , Hui Liu 1, * , Hui Wu 1 , Zhimin Yan 1 and Jing Zhao 1 1 Department of Neurology, Minhang Branch, Zhongshan Hospital, Fudan University, Shanghai, China * Co-first authors Correspondence to: Jing Zhao, email: zhaojinmhyy7@163.com Zhimin Yan, email: yanzhiminmh@163.com Keywords: OGDR; neuroprotection; Tanshinone IIA; AMP-activated protein kinase (AMPK); Ppm1e Received: October 27, 2017      Accepted: December 01, 2017      Published: December 17, 2017 ABSTRACT 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.