title: Carvedilol attenuates 6-hydroxydopamine-induced cell death in PC12 cells: involvement of Akt and Nrf2/ARE pathways.
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.
authors: Department of Neurology, Puai Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430033, China.
authors: Lan
authors: L
authors: Wang
authors: Rikang
authors: R
authors: Wang
authors: Minghua
authors: M
authors: Jin
authors: Yingjuan
authors: Y
authors: Huang
authors: Anmin
authors: A
authors: Liu
authors: Jian
authors: J
authors: Qin
authors: Meihui
authors: M
authors: Chen
authors: Shijun
authors: S
authors: Wen
authors: Rongbiao
authors: R
authors: Pi
authors: Wei
authors: W
authors: Shen
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D002227:Carbazoles / Q000494:pharmacology*; D000077261:Carvedilol; D016923:Cell Death / Q000187:drug effects*; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D016627:Oxidopamine / Q000633:toxicity; D016716:PC12 Cells; D011412:Propanolamines / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats
chemical_list: D000319:Adrenergic beta-Antagonists; D002227:Carbazoles; D051267:NF-E2-Related Factor 2; C495637:Nfe2l2 protein, rat; D011412:Propanolamines; D000077261:Carvedilol; D016627:Oxidopamine; D051057:Proto-Oncogene Proteins c-akt