The Neuroprotective Effect of Steroid Receptor Coactivator-Interacting Protein (SIP) in Astrocyte Model of 1-Methyl-4-Phenylpyridinium (MPP⁺)-Induced Parkinson’s Disease

Abstract

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/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.

Steroid Receptor Coactivator-Interacting Protein (SIP) Alleviates Ischemic Cerebral Infarction Damage Through the NF-κB Pathway

“…SIP reduces the inflammatory response by inactivating p65, accordingly suppressing acute pancreatitis-induced myocardial injury [10]. Furthermore, SIP overexpression alleviates 1-methyl-4-phenylpyridinium-induced cytotoxicity, inflammatory response and oxidative stress, and nuclear factor-κB activation ameliorate Parkinson's disease [11]. Injection of steroid receptor coactivator-interacting protein activating plasmid attenuates collagen deposition in myocardial infarct and peri-infarct areas in acute myocardial infarction rats and also reduces myocardial NF-κB p65 expression.…”

Effects of Medicinal Plants and Flavonoids on Parkinson's Disease, a Review on Basic and Clinical Evidences

“… 4 In addition, the contribution of nuclear factor κB (NF-κB), an effective key factor in expression of pro-inflammatory cytokines, to neuronal death in PD has been understood. 5 , 6 The harmful impact of inflammatory mediators including tumor necrosis factors-α, interlukin (IL)-1β and IL-6, oxygen free radicals and inducible nitric oxide synthase on dopaminergic cells in substantia nigra pars compacta has been also ducumented. 7 , 8 The drugs used for the cure of PD such as levodopa (L-dopa) and monoamine oxidase B (MAO B ) inhibitors and dopamine agonists mdulate the brain dopamine content or trigger intracellular signalings through activating the dopamine receptors.…”