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Cellular antioxidant adaptive survival response to 6-hydroxydopamine-induced nitrosative cell death in C6 glioma cells

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Author(s)
Chan LeeGyu Hwan ParkJung-Hee Jang
Keimyung Author(s)
Jang, Jung Hee
Department
Dept. of Pharmacology (약리학)
Journal Title
Toxicology
Issued Date
2011
Volume
283
Issue
2-3
Keyword
ApoptosisC6 glioma cellsHeme oxygenase-1NF-E2-related factor 2Nitrosative stressPeroxynitriteSelf-defense
Abstract
Parkinson’s disease (PD) is a progressive neurodegenerative movement disorder characterized by
selective loss of dopaminergic neurons in the substantia nigra. 6-Hydroxydopamine (6-OHDA) is a cate-
cholaminergic neurotoxin widely used to produce experimental models of PD and has been reported to
cause oxidative and/or nitrosative stress. In this study,we have investigated 6-OHDA-induced nitrosative
cell death and its self-defense mechanism in C6 glioma cells. Treatment of C6 cells with 6-OHDA
increased expression of inducible nitric oxide synthase (iNOS) and subsequent production of nitric
oxide (NO). Furthermore 6-OHDA treatment led to peroxynitrite generation and nitrotyrosine for-
mation. 6-OHDA-induced nitrosative stress ultimately caused apoptotic cell death as determined by
decreased Bcl-2/Bax ratio, activation of c-Jun N-termianl kinase (JNK), and cleavage of caspase-3 and
poly(ADP-ribose)polymerase (PARP), which were attenuated by peroxynitrite decomposition catalyst,
5,10,15,20-tetrakis(4-sulfonatophenyl)prophyrinato iron(III) (FeTPPS). In another experiment, exposure
of C6 glioma cells to 6-OHDA resulted in an increased expression of heme oxygenase-1 (HO-1) and 6-
OHDA-induced cytotoxicity was effectively suppressed by the HO-1 inducer SnCl2 and aggravated by
HO-1 inhibitor zinc protoporphyrin (ZnPP), supporting the cytoprotective role of HO-1. To elucidate the
molecular mechanism underlying 6-OHDA-mediated HO-1 induction, we have examined the possible
involvement of NF-E2-related factor 2 (Nrf2),which plays an important role in the transcriptional regula-
tion of phase II detoxifying and antioxidant enzymes. 6-OHDA treatment increased nuclear translocation
and transcriptional activity ofNrf2,which seemed to be partlymediated by activation of upstreamkinases
such as Akt/protein kinase B (PKB). Taken together these findings suggest that HO-1 up-regulation via
Nrf2 activation may mediate the cellular adaptive survival response to 6-OHDA-induced nitrosative cell
death in C6 glioma cells. Keywords:
Apoptosis
C6 glioma cells
Heme oxygenase-1
NF-E2-related factor 2
Nitrosative stress
Peroxynitrite
Self-defense
Keimyung Author(s)(Kor)
장정희
Publisher
School of Medicine
Citation
Chan Lee et al. (2011). Cellular antioxidant adaptive survival response to 6-hydroxydopamine-induced nitrosative cell death in C6 glioma cells. Toxicology, 283(2–3), 118–128. doi: 10.1016/j.tox.2011.03.004
Type
Article
ISSN
0300-483X
Source
http://lps3.www.sciencedirect.com.proxy.dsmc.or.kr/science/article/pii/S0300483X11000916?via%3Dihub
DOI
10.1016/j.tox.2011.03.004
URI
https://kumel.medlib.dsmc.or.kr/handle/2015.oak/34660
Appears in Collections:
1. School of Medicine (의과대학) > Dept. of Pharmacology (약리학)
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