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PBX1 attenuates 6-OHDA-induced oxidative stress and apoptosis and affects PINK1/PARKIN expression in dopaminergic neurons via FOXA1

Abstract

PBX1 expression has been found to be significantly reduced in nigrostriatal neurons of PD patients, but the effect of PBX1 on ROS and apoptosis in nigrostriatal dopamine neurons is not yet known. This paper aimed to explore whether PBX1 could be involved in the development of PD. The construction of the in vitro PD model was followed by the determination of PBX1 expression. Then, PBX1 was overexpressed to observe the changes in the cell viability, TH expression, oxidative stress and apoptosis of the model. The mitochondrial membrane potential analysis and detection of PINK1/parkin expression were also conducted. To observe whether FOXA1 was involved in the mechanism, its expression was measured, and its association with PBX1 was determined. Subsequently, FOXA1 was silenced to observe whether PBX1 did effects on dopaminergic neuron via FOXA1. PBX1 attenuates 6-OHDA-induced dopaminergic neuronal cell injury and oxidative stress, and apoptosis. Its overexpression ameliorates mitochondrial dysfunction in dopaminergic neurons and upregulates the expression of PINK1/parkin. PBX1 could combine with FOXA1 and affects 6-OHDA-induced dopaminergic neuronal damage and regulates PINK1/PARKIN expression via FOXA1. To conclude, PBX1 attenuates 6-OHDA-induced oxidative stress and apoptosis in dopaminergic neurons, and affected PINK1/PARKIN expression via FOXA1, which indicates the great potential of the PBX1 in prevention against PD.

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Data availability

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Correspondence to Shasha Zhu.

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Li, B., An, D. & Zhu, S. PBX1 attenuates 6-OHDA-induced oxidative stress and apoptosis and affects PINK1/PARKIN expression in dopaminergic neurons via FOXA1. Cytotechnology 74, 217–229 (2022). https://doi.org/10.1007/s10616-021-00518-8

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  • DOI: https://doi.org/10.1007/s10616-021-00518-8

Keywords

  • PBX1
  • FOXA1
  • PINK1/PARKIN
  • Parkinson’s disease (PD)