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

Authors
Jae-Hoon BaeByeong-Churl JangSeong-Il SuhEunyoung HaHyung Hwan BaikSung-Soo KimMi-young LeeDong-Hoon Shin
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)
Issue Date
2006
Citation
Neuroscience Letters, Vol.398(Issues 1-2) : 151-154, 2006
ISSN
0304-3940
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
Keywords
ManganeseiNOSPI 3-kinaseMAPKBV2 microglial cellsLuciferase assay
URI
http://kumel.medlib.dsmc.or.kr/handle/2015.oak/33537
Appears in Collections:
1. Journal Papers (연구논문) > 1. School of Medicine (의과대학) > Dept. of Biochemistry (생화학)
1. Journal Papers (연구논문) > 1. School of Medicine (의과대학) > Dept. of Microbiology (미생물학)
1. Journal Papers (연구논문) > 1. School of Medicine (의과대학) > Dept. of Molecular Medicine (분자의학)
1. Journal Papers (연구논문) > 1. School of Medicine (의과대학) > Dept. of Physiology (생리학)
1. Journal Papers (연구논문) > 1. School of Medicine (의과대학) > Dept. of Preventive Medicine (예방의학)
1. Journal Papers (연구논문) > 3. Research Institutues (연구소) > Institute for Medical Science (의과학연구소)
Keimyung Author(s)
배재훈; 장병철; 서성일; 하은영; 이미영; 신동훈
Full Text
http://lps3.www.sciencedirect.com.proxy.dsmc.or.kr/science/article/pii/S0304394005014758?via%3Dihub
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