BACKGROUND: The purpose of this study was to investigate the role and mechanism of steroid receptor coactivator-interacting protein (SIP) in an astrocyte model of 1-methyl-4-phenylpyridinium (MPP⁺)-induced Parkinson’s disease.

MATERIAL AND METHODS: To perform our study, a Parkinson’s disease cell model was established by treating the rat glioblastoma cell line C6 with MPP⁺. SIP was overexpressed in C6 cells using SIP-plasmid. Cell viability and apoptosis were analyzed using MTT assay and flow cytometer respectively. Tumor necrosis factor (TNF)-α and interleukin (IL)-1β levels were detected using enzyme linked immunosorbent assay and quantitative reverse transcription PCR. Besides, lactate dehydrogenase (LDH) release, reactive oxygen species (ROS) production, and superoxide dismutase (SOD) enzyme activity were determined in the present study. For protein and mRNA detection, western blot assay, and qRT-PCR were performed respectively.

RESULTS: SIP was decreased in MPP⁺-induced C6 cells. SIP overexpression relieved MPP⁺-induced cytotoxicity of C6 cells, displayed as increased cell viability and reduced cell apoptosis and reduced LDH release. Besides, SIP inhibited MPP⁺-induced inflammatory response and oxidative stress, evidenced by decreased levels of inflammatory factors (TNF-α and IL-1β), reduced ROS generation and enhanced SOD activity. Moreover, MPP⁺-induced nuclear factor-κB activation was inhibited by SIP overexpression.

CONCLUSIONS: SIP was downregulated in Parkinson’s disease and it played a protective role in the development Parkinson’s disease, thus may be a promising target for Parkinson’s disease treatment.

Keywords: Astrocytes, neurogenic inflammation, Intracellular Signaling Peptides and Proteins, Models, Biological, Neuroprotective Agents, Receptors, Steroid