Celastrol prevents cadmium‐induced neuronal cell death by blocking reactive oxygen species‐mediated mammalian target of rapamycin pathway

• DOI: 10.1111/bph.13655
• Publication Date: 2016-10-20T16:42:40Z
• Authors: Ruijie Zhang; Nana Zhang; Hai Zhang; Chunxiao Liu; Xiaoqing Dong; Xiaoxue Wang; Yu Zhu; Chong Xu; Lei Liu; Sijun Yang; Shile Huang; Long Chen
• Keywords: Celastrol; Viability assay

Background and Purpose Increasing evidence has suggested cadmium (Cd), as an inducer of ROS, is a potential pathogenic factor in human neurodegenerative diseases. Thus, it important to find effective interventions for Cd‐induced oxidative stress the CNS. Here, we have studied effects celastrol, plant‐derived triterpene, on ROS production cell death neuronal cells, induced by Cd. Experimental Approach PC12, SH‐SY5Y cells primary murine neurons were used study celastrol neuroprotection against Cd‐poisoning. changes viability, apoptosis, AMP‐activated protein kinase (AMPK)/mammalian target rapamycin (mTOR) pathway analysed Trypan blue exclusion, DAPI TUNEL staining, imaging, immunofluorescence staining Western blotting. Pharmacological genetic approaches employed investigate mechanisms underlying Cd neurotoxicity. Results Celastrol attenuated apoptosis suppressing activation mTOR, which was attributed preventing inactivation AMPK. Inhibition AMPK with compound C or expression dominant negative AMPKα prevented from hindering dephosphorylation AMPKα, mTOR apoptosis. knockdown potentiated prevention phosphorylation p70 S6 1/eukaryotic initiation 4E binding 1 induction mitochondrial ROS. Conclusions Implications thus attenuating may be promising agent