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Manganese induces inducible nitric oxide synthase (iNOS) expression via activation of both MAP kinase and PI3K/Akt pathways in BV2 microglial cells

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Author(s)
Jae-Hoon BaeByeong-Churl JangSeong-Il SuhEunyoung HaHyung Hwan BaikSung-Soo KimMi-young LeeDong-Hoon Shin
Keimyung Author(s)
Bae, Jae HoonJang, Byeong ChurlSuh, Seong IlHa, Eun YoungLee, Mi YoungShin, Dong Hoon
Department
Dept. of Physiology (생리학)
Dept. of Molecular Medicine (분자의학)
Dept. of Microbiology (미생물학)
Dept. of Biochemistry (생화학)
Dept. of Preventive Medicine (예방의학)
Institute for Medical Science (의과학연구소)
Journal Title
Neuroscience Letters
Issued Date
2006
Volume
398
Issue
Issues 1-2
Keyword
ManganeseiNOSPI 3-kinaseMAPKBV2 microglial cellsLuciferase assay
Abstract
It is well documented that manganese neurotoxicity induces clinical symptoms similar to those of idiopathic Parkinson’s disease. Although
microglial cytotoxic mediator-induced neurotoxicity is suggested, the mechanism by which manganese up-regulates cytotoxic mediator, such as
nitric oxide (NO), remains poorly understood. Therefore, in this study, we investigated the mechanism of manganese on induction of iNOS in
microglial cells. iNOS promoter/luciferase assay revealed that manganese (500 (M) regulated the iNOS expression at the transcriptional level.
Immunoblot analysis also revealed that phosphorylation levels of ERK, JNK MAPKs and Akt (PKB, PI 3-kinase downstream effector), were
increased. Both protein and mRNA levels of iNOS expression were abrogated by specific inhibitors, SP600125 (JNK inhibitor, 20 M), PD98059
(ERKs inhibitor, 50 M), or LY294002 (PI 3-kinase inhibitor, 20 M), but not by SB203580 (20 M), a p38 specific inhibitor. These data lead to
the conclusion that manganese regulates the iNOS expression at the transcriptional level in BV2 microglial cells and the increased iNOS protein
expression is mediated via both JNK-ERK MAPK and PI3K/Akt signaling pathways, but not via p38 MAPK pathway. Increased iNOS protein
level was also found in RAW264.7 murine macrophage cells.
© 2006 Elsevier Ireland Ltd. All rights reserved.
Keywords: Manganese; iNOS; PI 3-kinase; MAPK; BV2 microglial cells; Luciferase assay
Keimyung Author(s)(Kor)
배재훈
장병철
서성일
하은영
이미영
신동훈
Publisher
School of Medicine
Citation
Jae-Hoon Bae et al. (2006). Manganese induces inducible nitric oxide synthase (iNOS) expression via activation of both MAP kinase and PI3K/Akt pathways in BV2 microglial cells. Neuroscience Letters, 398(Issues 1-2), 151–154. doi: 10.1016/j.neulet.2005.12.067
Type
Article
ISSN
0304-3940
Source
http://lps3.www.sciencedirect.com.proxy.dsmc.or.kr/science/article/pii/S0304394005014758?via%3Dihub
DOI
10.1016/j.neulet.2005.12.067
URI
https://kumel.medlib.dsmc.or.kr/handle/2015.oak/33537
Appears in Collections:
1. School of Medicine (의과대학) > Dept. of Biochemistry (생화학)
1. School of Medicine (의과대학) > Dept. of Microbiology (미생물학)
1. School of Medicine (의과대학) > Dept. of Molecular Medicine (분자의학)
1. School of Medicine (의과대학) > Dept. of Physiology (생리학)
1. School of Medicine (의과대학) > Dept. of Preventive Medicine (예방의학)
3. Research Institutues (연구소) > Institute for Medical Science (의과학연구소)
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