Regulatory Role and Molecular Mechanism of Mammalian Sterile 20-Like Kinase 1 in 1-Methyl-4-Phenylpyridinium Ion–Induced Parkinson’s Disease Cell Model

Abstract

Parkinson’s disease (PD) is a multifactorial degenerative disease in the elder. Given the involvement of mammalian sterile 20-like kinase 1 (MST1) in PD, this article was to illustrate the mechanism of MST1 in 1-methyl-4-phenylpyridinium ion (MPP⁺)-induced PD cell model. Cells were treated with different concentrations of MPP⁺ to establish a PD cell model. Reverse transcription–quantitative polymerase chain reaction and Western blot revealed that MST1 expression and iron ion concentration increased, but cellular viability decreased with MPP⁺ concentration. Inhibition of MST1 decreased ferroptosis; increased cellular viability, iron ion content, and levels of glutathione peroxidase 4; and decreased reactive oxygen species and lactate dehydrogenase release. Upregulation of ferroptosis levels using ferroptosis agonist Erastin reduced the protective effect of MST1 inhibition on PD cells. Mechanistically, dual-luciferase analysis identified that miR-23b-3p targeted MST1 and inhibited its expression. Overexpression of miR-23b-3p inhibited MST1 levels, thereby reducing cellular ferroptosis and attenuating MPP⁺-induced cell injury. Collectively, MST1 expression increased with increasing MPP⁺ concentration, and miR-23b-3p targeted MST1 to reduce ferroptosis and MPP⁺-induced cell injury.