MZF1 alleviates oxidative stress and apoptosis induced by rotenone in SH-SY5Y cells by promoting RBM3 transcription

J Toxicol Sci. 2021;46(10):477-486. doi: 10.2131/jts.46.477.

Abstract

Objective: To investigate the protective effect of MZF1/RBM3 on rotenone-induced neuronal injury.

Methods: Rotenone (1 μM) was used to treat SH-SY5Y cells for 24 hr to simulate the cellular model of Parkinson's disease (PD), followed by detection of SH-SY5Y cell activities using MTT assay. MZF1 expression in rotenone-treated SH-SY5Y cells was detected by qRT-PCR and Western blot. MZF1 overexpression plasmid or MZF1 overexpression plasmid and RBM3 siRNA was transfected into SH-SY5Y cells, and then the expressions of MZF1 and RBM3 were detected. Oxidative stress (OS) in SH-SY5Y cells was detected using CMH2DCF-DA probes. Cell apoptosis rate was detected by flow cytometry. CHIP assay and dual-luciferase reporter assay were used to detect the binding between MZF1 and RBM3 promoter.

Results: The expression of MZF1 was significantly lower in the rotenone-induced SH-SY5Y cells. Overexpression of MZF1 significantly reduced OS and apoptosis in rotenone-induced SH-SY5Y cells. MZF1 was a transcription factor of RBM3, which promoted the transcription of RBM3, and knockdown of RBM3 inhibited the protective effect of MZF1 overexpression on SH-SY5Y cells.

Conclusion: MZF1 alleviates OS and apoptosis induced by rotenone in SH-SY5Y cells by promoting RBM3 transcription.

Keywords: Apoptosis; MZF1; Oxidative stress; RBM3; Rotenone.

MeSH terms

  • Apoptosis*
  • Cell Line, Tumor
  • Humans
  • Kruppel-Like Transcription Factors* / metabolism
  • Neurons
  • Oxidative Stress*
  • RNA-Binding Proteins* / genetics
  • Rotenone* / toxicity

Substances

  • Kruppel-Like Transcription Factors
  • MZF1 protein, human
  • RBM3 protein, human
  • RNA-Binding Proteins
  • Rotenone