Wnt2 overexpression protects against PINK1 mutant‑induced mitochondrial dysfunction and oxidative stress

Xia,Sui‑Rui; Wen,Xue‑Yi; Fan,Xiao‑Li; Chen,Xiao‑Rong; Wei,Zai‑Wa; Li,Qing‑Hua; Sun,Li

doi:10.3892/mmr.2020.11066

Wnt2 overexpression protects against PINK1 mutant‑induced mitochondrial dysfunction and oxidative stress

Authors:
- Sui‑Rui Xia
- Xue‑Yi Wen
- Xiao‑Li Fan
- Xiao‑Rong Chen
- Zai‑Wa Wei
- Qing‑Hua Li
- Li Sun
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Affiliations: Department of Hospital Infection‑Control, Nanxishan Hospital of Guangxi Zhuang Autonomous Region, Guilin, Guangxi 541002, P.R. China, Guangxi Key Laboratory of Brain and Cognitive Neuroscience, Guilin Medical University, Guilin, Guangxi 541004, P.R. China, Faculty of Basic Medical Sciences, Guilin Medical University, Guilin, Guangxi 541004, P.R. China
Published online on: April 8, 2020 https://doi.org/10.3892/mmr.2020.11066
Pages: 2633-2641

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Abstract

The PTEN induced putative kinase 1 (PINK1) mutation is the second most common cause of autosomal recessive adolescent Parkinson's disease (PD). Furthermore, mitochondrial disorders and oxidative stress are important mechanisms in the pathogenesis of PD. Numerous members of the Wnt family have been found to be associated with neurodegenerative diseases. Therefore, the present study investigated the role of the Wnt2 gene in PINK1B9 transgenic flies, which is a PD model, and its underlying mechanism. It was identified that overexpression of Wnt2 reduced the abnormality rate of PD transgenic Drosophila and improved their flight ability, while other intervention groups had no significant effect. Furthermore, an increase in ATP concentration normalized mitochondrial morphology, and increased the mRNA expression levels of NADH‑ubiquinone oxidoreductase chain 1 (ND1), ND42, ND75, succinate dehydrogenase complex subunits B, Cytochrome b and Cyclooxygenase 1, which are associated with Wnt2 overexpression. Moreover, overexpression of Wnt2 in PD transgenic Drosophila resulted in the downregulation of reactive oxygen species and malondialdehyde production, and increased manganese superoxide dismutase (MnSOD), while glutathione was not significantly affected. It was found that overexpression of Wnt2 did not alter the protein expression of β‑catenin in PINK1B9 transgenic Drosophila, but did increase the expression levels of PPARG coactivator 1α (PGC‑1α) and forkhead box sub‑group O (FOXO). Collectively, the present results indicated that the Wnt2 gene may have a protective effect on PD PINK1B9 transgenic Drosophila. Thus, it was speculated that the reduction of oxidative stress and the restoration of mitochondrial function via Wnt2 overexpression may be related to the PGC‑1α/FOXO/MnSOD signaling pathway in PINK1 mutant transgenic Drosophila.

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