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Inhibition of glycogen synthase kinase-3β by lithium chloride suppresses 6-hydroxydopamine-induced inflammatory response in primary cultured astrocytes.
Neurochem Int. 2013 Nov; 63(5):345-53.NI

Abstract

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-3β (GSK-3β) 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-α (TNF-α) were obviously increased in astrocytes exposed to 6-OHDA. Western blot analysis revealed that 6-OHDA significantly increased dephosphorylation/activation of GSK-3β as well as the nuclear translocation of nuclear factor-κB (NF-κB) p65. Besides, GSK-3β inhibitor LiCl and SB415286 inhibited the GSK-3β/NF-κB signaling pathway, leading to the reduction of proinflammatory molecules in 6-OHDA-activated astrocytes. These results confirmed that GSK-3β inhibitor LiCl and SB415286 provide protection against neuroinflammation in 6-OHDA-treated astrocytes. Therefore, GSK-3β may be a potential therapeutic target for the treatment of PD.

Authors+Show Affiliations

Department of Neurology, Shanghai Jiaotong University Affiliated Sixth People's Hospital, No. 600 Yishan Road, Shanghai 200233, China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23871716

Citation

Wang, Hong-Mei, et al. "Inhibition of Glycogen Synthase Kinase-3β By Lithium Chloride Suppresses 6-hydroxydopamine-induced Inflammatory Response in Primary Cultured Astrocytes." Neurochemistry International, vol. 63, no. 5, 2013, pp. 345-53.
Wang HM, Zhang T, Li Q, et al. Inhibition of glycogen synthase kinase-3β by lithium chloride suppresses 6-hydroxydopamine-induced inflammatory response in primary cultured astrocytes. Neurochem Int. 2013;63(5):345-53.
Wang, H. M., Zhang, T., Li, Q., Huang, J. K., Chen, R. F., & Sun, X. J. (2013). Inhibition of glycogen synthase kinase-3β by lithium chloride suppresses 6-hydroxydopamine-induced inflammatory response in primary cultured astrocytes. Neurochemistry International, 63(5), 345-53. https://doi.org/10.1016/j.neuint.2013.07.003
Wang HM, et al. Inhibition of Glycogen Synthase Kinase-3β By Lithium Chloride Suppresses 6-hydroxydopamine-induced Inflammatory Response in Primary Cultured Astrocytes. Neurochem Int. 2013;63(5):345-53. PubMed PMID: 23871716.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Inhibition of glycogen synthase kinase-3β by lithium chloride suppresses 6-hydroxydopamine-induced inflammatory response in primary cultured astrocytes. AU - Wang,Hong-Mei, AU - Zhang,Ting, AU - Li,Qiang, AU - Huang,Jian-Kang, AU - Chen,Rong-Fu, AU - Sun,Xiao-Jiang, Y1 - 2013/07/16/ PY - 2013/03/26/received PY - 2013/06/29/revised PY - 2013/07/07/accepted PY - 2013/7/23/entrez PY - 2013/7/23/pubmed PY - 2014/6/3/medline KW - 4′,6-diamidino-2-phenylindole, dihydrochloride KW - 6-OHDA KW - 6-hydroxydopamine KW - COX-2 KW - DAPI KW - GFAP KW - GSK KW - Glycogen synthase kinase-3β KW - IL-6 KW - LPS KW - LiCl KW - Lithium chloride KW - NF-κB KW - NO KW - Nuclear factor kappa B KW - PD KW - PGE2 KW - Parkinson’s disease KW - Proinflammatory molecules KW - SN KW - SNpc KW - TNF-α KW - cyclooxygenase-2 KW - glial fibrillary acidic protein KW - glycogen synthase kinase KW - iNOS KW - inducible nitric oxide synthase KW - interleukin-6 KW - lipopolysaccharide KW - lithium chloride KW - nitric oxide KW - nuclear factor kappa B KW - prostaglandins E2 KW - substantia nigra KW - substantia nigra pars compacta KW - tumor necrosis factor-α SP - 345 EP - 53 JF - Neurochemistry international JO - Neurochem Int VL - 63 IS - 5 N2 - 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-3β (GSK-3β) 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-α (TNF-α) were obviously increased in astrocytes exposed to 6-OHDA. Western blot analysis revealed that 6-OHDA significantly increased dephosphorylation/activation of GSK-3β as well as the nuclear translocation of nuclear factor-κB (NF-κB) p65. Besides, GSK-3β inhibitor LiCl and SB415286 inhibited the GSK-3β/NF-κB signaling pathway, leading to the reduction of proinflammatory molecules in 6-OHDA-activated astrocytes. These results confirmed that GSK-3β inhibitor LiCl and SB415286 provide protection against neuroinflammation in 6-OHDA-treated astrocytes. Therefore, GSK-3β may be a potential therapeutic target for the treatment of PD. SN - 1872-9754 UR - https://www.unboundmedicine.com/medline/citation/23871716/Inhibition_of_glycogen_synthase_kinase_3β_by_lithium_chloride_suppresses_6_hydroxydopamine_induced_inflammatory_response_in_primary_cultured_astrocytes_ DB - PRIME DP - Unbound Medicine ER -