Protective effects of activated signaling pathways by insulin on C6 glial cell model of MPP⁺-induced Parkinson’s disease

Abstract

Parkinson’s disease (PD) is the second most common neurodegenerative disorder after Alzheimer’s disease (AD) associated with mitochondrial dysfunction mediated by oxidative stress. Astrocytes regulate neuronal function via the modulation of synaptic transmission and plasticity, secretion of growth factors, uptake of neurotransmitters, and regulation of extracellular ion concentrations and metabolic support of neurons. Therefore, this study was undertaken to investigate the mechanism of action of insulin on a 1-methyl-4-phenylpyridinium (MPP⁺)-induced toxicity of events associated in cell viability and toxicity to the expression profile of cell signaling pathway proteins and genes in rat C6 glial cells. The various concentrations of MPP⁺ alone inhibited cell viability in a dose-dependent manner. Pretreatment of insulin prevented the cell death and lowered the intracellular reactive oxygen species and calcium ion influx by MPP⁺. Insulin also suppressed the α-synuclein and elevated the insulin signaling pathway molecules IR, IGF-1R, IRS-1 and IRS-2 in C6 cells through phosphorylation of Akt/ERK survival pathways. Moreover, insulin inhibits MPP⁺-induced Bax to Bcl-2 ratio. These results suggest that insulin has a protective effect on the MPP⁺-toxicity in C6 glial cells.

Keywords:

• Akt
• astrocytes
• Bcl-2
• ERK
• insulin signaling pathways

Disclosure statement

The authors have no conflicts of interest to declare.

Funding information

This study was supported by the Kyung Hee University (KHU-20150703) and Basic Science Research Program through the National Research Foundation of Korea (NRF), which is funded by the Korean Ministry of Education, Science and Technology (2013R1A1A2006613).