Amphetamine Neurotoxicity in PC12 Cells through the PP2A/AKT/GSK3 beta Pathway

作者：He, Wenji; Yan, Xinyu; Pan, Sanqiang^*

来源：Neurotoxicity Research, 2018, 34(2): 233-240.

DOI：10.1007/s12640-018-9880-8

• Amphetamine
• Neurotoxicity
• Protein kinase B
• Glycogen synthase kinase 3
• Protein phosphatase 2

Amphetamine (AMPH) abuse can influence neuropsychiatric disorders and cell apoptosis by interfering with the protein kinase B/glycogen synthase kinase 3 beta (AKT/GSK3 beta) pathway. However, the mechanisms underlying this regulation are poorly understood. Using PC12 cells, we found that AMPH inhibited AKT and GSK-3 beta phosphorylation levels and increased total GSK-3 beta levels. Furthermore, AMPH caused an increase in the activity of protein phosphatase 2 (PP2A), a signaling protein upstream of AKT, which in turn inhibited phosphorylated AKT levels. Okadaic acid, a PP2A inhibitor, protected PC12 cells against AMPH-induced apoptosis. Together, our results suggest that the PP2A/AKT/GSK3 beta pathway plays an important role in AMPH-induced neurotoxicity.

• 出版日期2018-8
• 单位赣南医学院; 暨南大学