Manganese induces inducible nitric oxide synthase (iNOS) expression via activation of both MAP kinase and PI3K/Akt pathways in BV2 microglial cells
- Author(s)
- Jae-Hoon Bae; Byeong-Churl Jang; Seong-Il Suh; Eunyoung Ha; Hyung Hwan Baik; Sung-Soo Kim; Mi-young Lee; Dong-Hoon Shin
- Keimyung Author(s)
- Bae, Jae Hoon; Jang, Byeong Churl; Suh, Seong Il; Ha, Eun Young; Lee, Mi Young; Shin, 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
- Manganese; iNOS; PI 3-kinase; MAPK; BV2 microglial cells; Luciferase 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
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