P90RSK and Nrf2 Activation via MEK12-ERK12 Pathways Mediated by Notoginsenoside R2 to Prevent 6-Hydroxydopamine-Induced Apoptotic Death in SH-SY5Y Cells
Joint Authors
Sun, Xiao-Bo
Sun, Jing
Wang, Min
Sun, Gui-Bo
Meng, Xiang-Bao
Qin, Meng
Source
Evidence-Based Complementary and Alternative Medicine
Issue
Vol. 2013, Issue 2013 (31 Dec. 2013), pp.1-15, 15 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2013-09-18
Country of Publication
Egypt
No. of Pages
15
Main Subjects
Abstract EN
6-Hydroxydopamine (6-OHDA) is known to contribute to neuronal death in Parkinson's disease.
In this study, we found that the preincubation of SH-SY5Y cells for 24 h with 20 μM notoginsenoside R2 (NGR2), which is a newly isolated notoginsenoside from Panax notoginseng, showed neuroprotective effects against 6-OHDA-induced oxidative stress and apoptosis.
NGR2 incubation successively resulted in the activation of P90RSK, inactivation of BAD, and inhibition of 6-OHDA-induced mitochondrial membrane depolarization, thus preventing the mitochondrial apoptosis pathway.
NGR2 incubation also led to the activation of Nrf2 and subsequent activity enhancement of phase II detoxifying enzymes, thus suppressing 6-OHDA-induced oxidative stress, and these effects could be removed by Nrf2 siRNA.
We also found that the upstream activators of P90RSK and Nrf2 were the MEK1/2–ERK1/2 pathways but not the JNK, P38, or PI3K/Akt pathways.
Interestingly, NGR2 incubation could also activate MEK1/2 and ERK1/2.
Most importantly, NGR2-mediated P90RSK and Nrf2 activation, respective downstream target activation, and neuroprotection were reversed by the genetic silencing of MEK1/2 and ERK1/2 by using siRNA and PD98059 application.
These results suggested that the neuroprotection elicited by NGR2 against 6-OHDA-induced neurotoxicity was associated with NGR2-mediated P90RSK and Nrf2 activation through MEK1/2-ERK1/2 pathways.
American Psychological Association (APA)
Meng, Xiang-Bao& Sun, Gui-Bo& Wang, Min& Sun, Jing& Qin, Meng& Sun, Xiao-Bo. 2013. P90RSK and Nrf2 Activation via MEK12-ERK12 Pathways Mediated by Notoginsenoside R2 to Prevent 6-Hydroxydopamine-Induced Apoptotic Death in SH-SY5Y Cells. Evidence-Based Complementary and Alternative Medicine،Vol. 2013, no. 2013, pp.1-15.
https://search.emarefa.net/detail/BIM-512478
Modern Language Association (MLA)
Meng, Xiang-Bao…[et al.]. P90RSK and Nrf2 Activation via MEK12-ERK12 Pathways Mediated by Notoginsenoside R2 to Prevent 6-Hydroxydopamine-Induced Apoptotic Death in SH-SY5Y Cells. Evidence-Based Complementary and Alternative Medicine No. 2013 (2013), pp.1-15.
https://search.emarefa.net/detail/BIM-512478
American Medical Association (AMA)
Meng, Xiang-Bao& Sun, Gui-Bo& Wang, Min& Sun, Jing& Qin, Meng& Sun, Xiao-Bo. P90RSK and Nrf2 Activation via MEK12-ERK12 Pathways Mediated by Notoginsenoside R2 to Prevent 6-Hydroxydopamine-Induced Apoptotic Death in SH-SY5Y Cells. Evidence-Based Complementary and Alternative Medicine. 2013. Vol. 2013, no. 2013, pp.1-15.
https://search.emarefa.net/detail/BIM-512478
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-512478