Please use this identifier to cite or link to this item: http://hdl.handle.net/11455/70805
標題: Induction of cyclooxygenase-2 expression by manganese in cultured astrocytes
作者: Liao, S.L.
Ou, Y.C.
Chen, S.Y.
Chiang, A.N.
Chen, C.J.
關鍵字: astrocytes
cyclooxygenase
inflammation
manganese
neurodegeneration
oxidative stress
protein-kinase-c
nf-kappa-b
cytosolic phospholipase a(2)
central-nervous-system
nitric-oxide
parkinsons-disease
alzheimers-disease
gene-expression
prostaglandin synthase
immune-responses
期刊/報告no:: Neurochemistry International, Volume 50, Issue 7-8, Page(s) 905-915.
摘要: Inflammatory and oxidative events are present in neurodegenerative disorders and appear to contribute to initiation and/or progression of the disease. Within the brain, redox-active metals, such as manganese, play an important role as components of proteins essential for neural function. However, increasing evidence implies its participation in neurodegenerative diseases involving immune modulation. Prostaglandins (PGs) are lipid mediators that participate in the regulation of physiological and pathophysiological processes, particularly during brain inflammation. In this study, we investigated whether the immune modulating action of manganese involved regulation of PGE2 production in cortical astrocytes. Within nontoxic concentrations, manganese caused an elevation in the expression of cyclooxygenase-2 (COX-2) mRNA and protein and increased PGE2 release. Manganese potentiated COX-2 expression and PGE2 generation by lipopolysaccharide/interferon-gamma-activated astrocytes. The inductive action of manganese was accompanied by generation of oxidative stress, activation of mitogen-activated protein kinases (MAPKs), AKT, and protein kinase C-a (PKC-a), and increased NF-KB and AP-1 DNA binding activities. The generation of reactive oxygen species (ROS) was critical to manganese-induced changes in astrocytes, including MAPKs, PKC-a, NF-KB, AP-1, and COX-2 expression but not AKT. Collectively, these data indicate that manganese might cause changes in neural activity through the modulation of oxidative and inflammatory events in astrocytes. (C) 2006 Elsevier Ltd. All rights reserved.
URI: http://hdl.handle.net/11455/70805
ISSN: 0197-0186
文章連結: http://dx.doi.org/10.1016/j.neuint.2006.09.016
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