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Activation of Wnt/β-catenin Pathway by Exogenous Wnt1 Protects SH-SY5Y Cells Against 6-Hydroxydopamine Toxicity

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Abstract

Wnt1, initially described as a modulator of embryonic development, has recently been discovered to exert cytoprotective effects in cellular models of several diseases, including Parkinson's disease (PD). We, therefore, examined the neuroprotective effects of exogenous Wnt1 on dopaminergic SH-SY5Y cells treated with 6-hydroxydopamine (6-OHDA). Here, we show that 10–500 μM 6-OHDA treatment decreased cell viability and increased lactate dehydrogenase (LDH) leakage. SH-SY5Y cells treated with 100 μM 6-OHDA for 24 h showed reduced Wnt/β-catenin activity, decreased mitochondrial transmembrane potential, elevated levels of reactive oxidative species (ROS) and phosphatidylserine (PS) extraversion, increased levels of Chop and Bip/GRP78 and reduced level of p-Akt (Ser473). In contrast, exogenous Wnt1 attenuated 6-OHDA-induced changes. These results suggest that activation of the Wnt/β-catenin pathway by exogenous Wnt1 protects against 6-OHDA-induced changes by restoring mitochondria and endoplasmic reticulum (ER) function.

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Acknowledgments

We thank Dr. D. Walsh (Harvard Medical School) for careful reading and correction of this manuscript. This work was supported by “863” project (2007AA02Z460), “973” project (2010AB973Z531) from the Ministry of Science and Technology of the People's Republic of China, grants from Nature Science Foundation of China (81071032, 81271428), the Guangzhou Foundation for Scientific and Technological Project, China (grant no. 2012J4300061), the Specialized Research Fund for the Doctoral Program of Higher Education of China (grant no. 20100171110056), and a grant supported by a key project (ZDXM080214) from Hainan Provincial Science and Technology Department.

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Authors and Affiliations

  1. Department of Neurology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080, People’s Republic of China

    Lei Wei, Congcong Sun, Ming Lei, Zhuolin Liu & Pingyi Xu

  2. Department of Neurology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510630, People’s Republic of China

    Lei Wei

  3. Department of Neurology, Henan University Hospital of Huaihe, Kaifeng, Henan, 37500, People’s Republic of China

    Guofei Li

  4. Department of Neurology, Shenzhen Hospital of Beijing University, Shenzhen, 518036, People’s Republic of China

    Li Yi

  5. Department of Neurology, The Second Affiliated Hospital of Chengdu, Chongqing Medical University/The Third People’s Hospital of Chengdu, Chengdu, 610031, People’s Republic of China

    Feifei Luo

  6. Department of Neurology, Guangzhou Red Cross Hospital, The Forth Affiliated Hospital of Jinan University, Guangzhou, 510220, People’s Republic of China

    Yi Li

  7. Department of Pathology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080, People’s Republic of China

    Li Ding

  8. Department of Neurology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, 02115, USA

    Shaomin Li

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  1. Lei Wei
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Correspondence to Shaomin Li or Pingyi Xu.

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Lei Wei, Congcong Sun, Guofei Li, and Ming Lei contributed equally to this work.

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Wei, L., Sun, C., Lei, M. et al. Activation of Wnt/β-catenin Pathway by Exogenous Wnt1 Protects SH-SY5Y Cells Against 6-Hydroxydopamine Toxicity. J Mol Neurosci 49, 105–115 (2013). https://doi.org/10.1007/s12031-012-9900-8

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