Yin Yang 1 suppresses apoptosis and oxidative stress injury in SH-SY5Y cells by facilitating NR4A1 expression

Abstract

Oxidative stress plays a significant role in the development of Parkinson’s disease (PD). Previous studies implicate nuclear receptor subfamily 4 group A member 1 (NR4A1) in oxidative stress associated with PD. However, the molecular mechanism underlying the regulation of NR4A1 expression remains incompletely understood. In the present study, a PD cell model was established by using 1-methyl-4-phenylpyridinium (MPP⁺) in SH-SY5Y cells. Cell viability and apoptosis were assessed by using CCK-8 assay and flow cytometry, respectively. The activities of LDH and SOD, and ROS generation were used as an indicators of oxidative stress. ChIP-PCR was performed to detect the interaction between Yin Yang 1 (YY1) and the NR4A1 promoter. MPP⁺ treatment inhibited SH-SY5Y cell viability in a dose- and time-dependent manner. NR4A1 and YY1 expression were decreased in MPP⁺-treated SH-SY5Y cells. Increasing NR4A1 or YY1 alleviated MPP⁺-induced apoptosis and oxidative stress in SH-SY5Y cells, whereas reduction of NR4A1 aggravated MPP⁺-induced cell injury. Transcription factor YY1 facilitated NR4A1 expression by binding with NR4A1 promoter. In addition, in MPP⁺-treated SH-SY5Y cells, the inhibition of NR4A1 to apoptosis and oxidative stress was further enhanced by overexpression of YY1. The reduction of NR4A1 led to an elevation of apoptosis and oxidative stress in MPP⁺-induced SH-SY5Y cells, and this effect was partially reversed by the overexpression of YY1. In conclusion, YY1 suppresses MPP⁺-induced apoptosis and oxidative stress in SH-SY5Y cells by binding with NR4A1 promoter and boosting NR4A1 expression. Our findings suggest that NR4A1 may be a candidate target for PD treatment.

HIGHLIGHTS

1. NR4A1 and YY1 are decreased in MPP⁺-treated SH-SY5Y cells.

2. NR4A1 prevents oxidative stress and apoptosis in MPP⁺-treated SH-SY5Y cells.

3. YY1 binds with NR4A1 promoter and increases NR4A1 expression.

4. YY1 enhances the inhibition of NR4A1 to SH-SY5Y cell apoptosis and oxidative stress.

Keywords:

• Parkinson’s disease
• nuclear receptor subfamily 4 group A member 1
• Yin Yang 1
• oxidative stress
• cell apoptosis

Acknowledgements

We thank members of the laboratory for comments and discussions.

Disclosure statement

No potential conflict of interest was reported by the authors.

Data availability statement

The data underlying this article will be shared on reasonable request to the corresponding author.

Additional information

Funding

The author(s) reported there is no funding associated with the work featured in this article.