期刊
NEUROCHEMISTRY INTERNATIONAL
卷 63, 期 5, 页码 345-353出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neuint.2013.07.003
关键词
Glycogen synthase kinase-3 beta; Lithium chloride; Nuclear factor kappa B; Parkinson's disease; Proinflammatory molecules
资金
- National Natural Science Foundation of China [81100953, 31100783, 31171014]
An increasing amount of evidence has emerged to suggest that neuroinflammatory process is involved in the pathogenesis of Parkinson's disease (PD). Activated microglia and astrocytes are found in the substantia nigra (SN) of Parkinson's disease brains as well as in animal models of Parkinson's disease. Although reactive astrocytes are involved in the progression of PD, the role of reactive astrocytes in neuroinflammation of PD has received limited attention to date. Recently, Glycogen synthase kinase-3 beta (GSK-3 beta) was identified as a crucial regulator of the inflammatory response. The purpose of this study was to explore the mechanism by which 6-hydroxydopamine (6-OHDA) induces inflammatory response in astrocytes and observe the anti-inflammatory effect of lithium chloride (LiCl) on 6-OHDA-treated astrocytes. In the present study, we found that glial fibrillary acidic protein (GFAP) was markedly upregulated in the presence of 6-OHDA. Moreover, our results revealed that proinflammatory molecules including inducible nitric oxide synthase (iNOS), nitric oxide (NO), cyclooxygenase-2(COX-2), prostaglandins E2 (PGE2), and tumor necrosis factor-alpha (TNF-alpha) were obviously increased in astrocytes exposed to 6-OHDA. Western blot analysis revealed that 6-OHDA significantly increased dephosphorylation/activation of GSK-3 beta as well as the nuclear translocation of nuclear factor-kappa B (NF-kappa B) p65. Besides, GSK-3 beta inhibitor LiCl and SB415286 inhibited the GSK-3 beta/NF-kappa B signaling pathway, leading to the reduction of proinflammatory molecules in 6-OHDA-activated astrocytes. These results confirmed that GSK-3 beta inhibitor LiCl and SB415286 provide protection against neuroinflammation in 6-OHDA-treated astrocytes. Therefore, GSK-3 beta may be a potential therapeutic target for the treatment of PD. (C) 2013 Published by Elsevier Ltd.
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