AMPK activation by Tanshinone IIA protects neuronal cells from oxygen-glucose deprivation
| Autor: | Hui Liu, Jing Zhao, Zhimin Yan, Jixian Lin, Hui Wu, Yingfeng Weng |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
chemistry.chemical_classification Reactive oxygen species Gene knockdown Chemistry AMPK Depolarization Tanshinone IIA Neuroprotection Cell biology 03 medical and health sciences 030104 developmental biology Ppm1e Oncology Downregulation and upregulation Apoptosis AMP-activated protein kinase (AMPK) OGDR neuroprotection Protein kinase A Research Paper |
| Zdroj: | Oncotarget |
| ISSN: | 1949-2553 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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