Astragaloside-IV regulates endoplasmic reticulum stress-mediated neuronal apoptosis in a murine model of Parkinson's disease via the lincRNA-p21/CHOP pathway

Abstract

ObjectivesAstragaloside-IV (AS-IV) protects the nerve cells of Parkinson's disease (PD) from damage. Long non-coding RNA (lincRNA) has been found to be important for many diseases. Lincnra-p21 is abnormally expressed in PD. The purpose of this study was to investigate whether Astragaloside-IV (AS-IV) affects endoplasmic reticulum stress (ERS)-induced neuronal apoptosis in PD, and its possible mechanisms. MethodsThe PD mouse model was established via injecting 1-methyl-4-phenyl-1, 2, 3, 6- tetrahydropyridine (MPTP) and the PD cell model was established via inducing the MN9D cell line with 1-methyl-4-pehnyl-pyridine (MPP+). The behavioral testing of PD model mice was tested after AS-IV treatment and PD-related lincRNAs expression were detected by qRT-PCR. After treatment of PD model cells with AS-IV, lincRNA-p21 expression was detected by qRT-PCR, and cell viability and apoptosis were detected by MTT assay and flow cytometry, respectively. The binding of lincRNA-p21 to C/EBP-homologous (CHOP) protein was investigated by RNA immunoprecipitation and RNA pull-down, and the effect of lincRNA-p21 on the ubiquitination of CHOP protein was examined by ubiquitination assay. The role of lincRNA-p21 in PD model was studied by cell transfection. ResultsIn PD mice, AS-IV can improve the behavior of mice and significantly inhibit expression of lincRNA-p21. Similarly, AS-IV can obviously restrain the expression of lincRNA-p21 in PD cells, and obviously elevated cell viability and restrained apoptosis. LincRNA-p21 is able to bind to CHOP protein. Further studies showed that restraint of lincRNA-p21 expression can facilitate ubiquitination of CHOP and accelerate its protein degradation. In AS-IV-treated PD model cells, overexpression of lincRNA-p21 lessened cell viability and facilitated apoptosis, whereas low expression of CHOP reversed this result. ConclusionIn this study, we found that AS-IV can lessen the expression of CHOP protein by restraining the expression of lincRNA-p21 in the PD model, thereby inhibiting neuronal apoptosis.