title: 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.
authors.affiliation: a Department of Pharmacology and Toxicology, Metabolic Diseases Research Laboratory, School of Dentistry , Kyung Hee University , Seoul , South Korea.
authors.forename: Mahesh
authors.initials: M
authors.lastname: Ramalingam
authors.affiliation: a Department of Pharmacology and Toxicology, Metabolic Diseases Research Laboratory, School of Dentistry , Kyung Hee University , Seoul , South Korea.
authors.forename: Sung-Jin
authors.initials: SJ
authors.lastname: Kim
mesh_terms: D015655:1-Methyl-4-phenylpyridinium / Q000633:toxicity*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D005909:Glioblastoma / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D006540:Herbicides / Q000633:toxicity; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects; D010300:Parkinson Disease / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects*; D014407:Tumor Cells, Cultured
chemical_list: D006540:Herbicides; D007004:Hypoglycemic Agents; D007328:Insulin; D015655:1-Methyl-4-phenylpyridinium
keywords: Akt; Bcl-2; ERK; astrocytes; insulin signaling pathways