Abstract
As a typical traditional Chinese medicine, Bu-Yin-Qian-Zheng Formula (BYQZF) has been shown to have neuroprotective effects in patients with Parkinson’s disease (PD), particularly by ameliorating mitochondrial dysfunction and regulating expression of the parkin protein. However, the underlying mechanisms by which BYQZF affects mitochondrial function through parkin are unclear. Accordingly, in this study, we evaluated the mechanisms by which BYQZF ameliorates mitochondrial dysfunction through parkin in PD. We constructed a parkin-knockdown cell model and performed fluorescence microscopy to observe transfected SH-SY5Y cells. Quantitative real-time reverse transcription polymerase chain reaction and western blotting were conducted to detect the mRNA and protein expression levels of parkin. Additionally, we evaluated the cell survival rates, ATP levels, mitochondrial membrane potential (ΔΨm), mitochondrial morphology, parkin protein expression, PINK1 protein expression, and mitochondrial fusion and fission protein expression after treatment with MPP+ and BYQZF. Our results showed that cell survival rates, ATP levels, ΔΨm, mitochondrial morphology, parkin protein levels, PINK1 protein levels, and mitochondrial fusion protein levels were reduced after MPP+ treatment. In contrast, mitochondrial fission protein levels were increased after MPP+ treatment. Moreover, after transient transfection with a negative control plasmid, the above indices were significantly increased by BYQZF. However, there were no obvious differences in these indices after transient transfection with a parkin-knockdown plasmid. Our findings suggest that BYQZF has protective effects on mitochondrial function in MPP+-induced SH-SY5Y cells via parkin-dependent regulation of mitochondrial dynamics.
Highlights
Parkinson’s disease (PD) is a common progressive neurodegenerative disease manifested by motor and nonmotor symptoms (Kalia and Lang, 2015) with degeneration of dopaminergic neurons in the substantia nigra pars compacta (Song et al, 2010; Ham et al, 2020)
We found that the mitochondrial form factor, mean length and number of mitochondrial network branches, mitochondrial activity, and expression of MFN2 protein were decreased, whereas dynamin-related protein 1 (DRP1) and fission mitochondrial 1 (FIS1) expression levels were increased in the parkin-knockdown control group
We evaluated the potential mechanisms by which Bu-Yin-Qian-Zheng Formula (BYQZF) ameliorated mitochondrial dysfunction by regulating mitochondrial dynamics via parkin in PD
Summary
Parkinson’s disease (PD) is a common progressive neurodegenerative disease manifested by motor and nonmotor symptoms (Kalia and Lang, 2015) with degeneration of dopaminergic neurons in the substantia nigra pars compacta (Song et al, 2010; Ham et al, 2020). Mitochondrial dysfunction has been shown to play a central role in the pathogenesis of PD (Exner et al, 2012). Mutation or deletion of the gene encoding parkin can trigger accumulation of dysfunctional mitochondria (Bankapalli et al, 2020) and cause the death of dopaminergic neurons in PD (Zhu et al, 2018). Because of the substantial role of mitochondrial dysfunction in PD, mitochondrion-targeted therapeutics may facilitate the development of novel drugs for treating PD (Camilleri and Vassallo, 2014; Park et al, 2018; Grünewald et al, 2019; Bai et al, 2020), and parkin may be an important mitochondrial target for expanding our understanding of the molecular mechanisms of mitochondrial dysfunction in PD therapy
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