Involvement of C/EBP β-related signaling pathway in methamphetamine-induced neuronal autophagy and apoptosis.

Involvement of C/EBPβ-related signaling pathway in methamphetamine-induced neuronal autophagy and apoptosis. Toxicol Lett. 2019 May 03;: Authors: Huang E, Huang H, Guan T, Liu C, Qu D, Xu Y, Yang J, Yan L, Xiong Y, Liang T, Wang Q, Chen L Abstract Methamphetamine (METH) is a widely abused illicit psychoactive drug. Our previous study has shown that CCAAT-enhancer binding protein β (C/EBPβ) is an important regulator in METH-induced neuronal autophagy and apoptosis. However, the detailed molecular mechanisms underlying this process remain poorly understood. Previous studies have demonstrated that DNA damage-inducible transcript 4 (DDIT4), Trib3 (tribbles pseudo kinase 3), alpha-synuclein (α-syn) are involved in METH-induced dopaminergic neurotoxicity. We hypothesized that C/EBPβ is involved in METH-induced DDIT4-mediated neuronal autophagy and Trib3-mediated neuronal apoptosis. We tested our hypothesis by examining the effects of silencing C/EBPβ, DDIT4, Trib3 or α-syn with small interfering ribonucleic acid (siRNA) on METH-induced autophagy and apoptosis in the human neuroblastoma SH-SY5Y cells. We also measured the levels of phosphorylated tuberous sclerosis complex 2 (TSC2) protein and Parkin protein level in SH-SY5Y cells. Furthermore, we demonstrated the effect of silencing C/EBPβ on METH-caused neurotoxicity in the striatum of rats by injecting LV-shC/EBPβ lentivirus using a stereotaxic positioning system. The results sh...
Source: Toxicology Letters - Category: Toxicology Authors: Tags: Toxicol Lett Source Type: research