Carvedilol Attenuates 6-Hydroxydopamine-Induced Cell Death in PC12 Cells: Involvement of Akt and Nrf2/ARE Pathways |
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Authors: | Lan Wang Rikang Wang Minghua Jin Yingjuan Huang Anmin Liu Jian Qin Meihui Chen Shijun Wen Rongbiao Pi Wei Shen |
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Institution: | 1. Department of Neurology, Puai Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430033, China 2. Department of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, China 3. Department of Traditional Chinese Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China 4. Department of Neurosurgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, China
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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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