Carvedilol, a third-generation β-blocker prevents oxidative stress-induced neuronal death and activates Nrf2/ARE pathway in HT22 cells.
Carvedilol, a nonselective β-adrenoreceptor blocker with pleiotropic activities has been shown to exert neuroprotective effect due to its antioxidant property. However, the neuroprotective mechanism of carvedilol is still not fully uncovered. Nuclear factor E2-related factor 2 (Nrf2)/antioxidant response element (ARE) pathway is an important cellular stress response pathway involved in neuroprotection. Here we investigated the effect of carvedilol on oxidative stress-induced cell death (glutamate 2mM and H2O2 600 μM) and the activity of Nrf2/ARE pathway in HT22 hippocampal cells. Carvedilol significantly increased cell viability and decreased ROS in HT22 cells exposed to glutamate or H2O2. Furthermore, carvedilol activated the Nrf2/ARE pathway 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. Collectively, our results indicate that carvedilol protects neuronal cell against glutamate- and H2O2-induced neurotoxicity possibly through activating the Nrf2/ARE signaling pathway.
Department of Pediatrics, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China.
Ying
Y
Ouyang
Ziwei
Z
Chen
Min
M
Tan
Anmin
A
Liu
Meihui
M
Chen
Jun
J
Liu
Rongbiao
R
Pi
Jianpei
J
Fang
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D061745:Antioxidant Response Elements; D002227:Carbazoles / Q000494:pharmacology*; D000077261:Carvedilol; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D018698:Glutamic Acid / Q000494:pharmacology; D051547:Heme Oxygenase-1 / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000494:pharmacology; D051379:Mice; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects* / Q000235:genetics; D011412:Propanolamines / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction
D000319:Adrenergic beta-Antagonists; D002227:Carbazoles; D051267:NF-E2-Related Factor 2; D018696:Neuroprotective Agents; C495636:Nfe2l2 protein, mouse; D011412:Propanolamines; D017382:Reactive Oxygen Species; D000077261:Carvedilol; D018698:Glutamic Acid; D006861:Hydrogen Peroxide; D051547:Heme Oxygenase-1
Carvedilol; Cell death; Heme oxygenase-1; Nuclear factor E2-related factor 2; Oxidative stress