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Carvedilol Attenuates 6-Hydroxydopamine-Induced Cell Death in PC12 Cells: Involvement of Akt and Nrf2/ARE Pathways

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Abstract

Oxidative stress is closely related to the pathogenesis of neurodegenerative disorders such as Parkinson’s disease. Carvedilol, a nonselective β-adrenergic receptor blocker with pleiotropic activity has been shown to exert neuroprotective effect due to its antioxidant property. However, the neuroprotective mechanism of carvedilol is still not fully uncovered. The phosphotidylinositol 3-kinase (PI3K)/Akt signaling pathway plays key role in cell survival and the nuclear factor erythroid 2–related factor 2 (Nrf2)/antioxidant response element (ARE) signaling pathway is the major cellular defense mechanism against oxidative stress. Here we investigated the effects of carvedilol on 6-hydroxydopamine (6-OHDA)-induced cell death as well as the Akt and Nrf2/ARE pathways in PC12 cells. We found that carvedilol significantly increased cell viability and decreased reactive oxygen species in PC12 cells exposed to 6-OHDA. Furthermore, carvedilol activated the Akt and Nrf2/ARE pathways in a concentration-dependent manner, and increased the protein levels of heme oxygenase-1(HO-1) and NAD(P)H quinone oxidoreductase-1(NQO-1), two downstream factors of the Nrf2/ARE pathway. In summary, our results indicate that carvedilol protects PC12 cells against 6-OHDA-induced neurotoxicity possibly through activating the Akt and Nrf2/ARE signaling pathways.

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Acknowledgments

This study was supported by National Natural Science Foundation of China/RGC Hong Kong Joint Research Scheme (No. 30731160617), Guangdong Provincial International Cooperation Project of Science & Technology (No. 2012B050300015) to R. Pi and The Program for Science and Technology of Wuhan (No. 2013062301010816) to L. Wang.

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Authors and Affiliations

  1. Department of Neurology, Puai Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430033, China

    Lan Wang & Wei Shen

  2. Department of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, China

    Rikang Wang, Meihui Chen, Shijun Wen & Rongbiao Pi

  3. Department of Traditional Chinese Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China

    Minghua Jin, Yingjuan Huang & Jian Qin

  4. Department of Neurosurgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, China

    Anmin Liu

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  1. Lan Wang
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  2. Rikang Wang
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  3. Minghua Jin
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Corresponding authors

Correspondence to Rongbiao Pi or Wei Shen.

Additional information

Lan Wang and Rikang Wang have contributed equally to this work.

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Wang, L., Wang, R., Jin, M. et al. Carvedilol Attenuates 6-Hydroxydopamine-Induced Cell Death in PC12 Cells: Involvement of Akt and Nrf2/ARE Pathways. Neurochem Res 39, 1733–1740 (2014). https://doi.org/10.1007/s11064-014-1367-2

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  • DOI: https://doi.org/10.1007/s11064-014-1367-2

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