Glycogen synthase kinase-3β indirectly facilitates interferon-γ-induced nuclear factor-κB activation and nitric oxide biosynthesis

2010 ◽  
Vol 111 (6) ◽  
pp. 1522-1530 ◽  
Author(s):  
Jui-In Kai ◽  
Wei-Ching Huang ◽  
Cheng-Chieh Tsai ◽  
Wen-Teng Chang ◽  
Chia-Ling Chen ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Glycogen Synthase ◽  
Nuclear Factor Κb ◽  
Interferon Γ ◽  
Glycogen Synthase Kinase ◽  
Nuclear Factor ◽  
Glycogen Synthase Kinase 3Β

scholarly journals Glycogen Synthase Kinase 3β-Mediated Apoptosis of Primary Cortical Astrocytes Involves Inhibition of Nuclear Factor κB Signaling

2003 ◽  
Vol 23 (13) ◽  
pp. 4649-4662 ◽  
Author(s):  
Joseph F. Sanchez ◽  
Lynn F. Sniderhan ◽  
Andrea L. Williamson ◽  
Shongshan Fan ◽  
Shikha Chakraborty-Sett ◽  
...  
Keyword(s):  
Cell Fate ◽  
Glycogen Synthase ◽  
Nuclear Factor Κb ◽  
Glycogen Synthase Kinase ◽  
Nuclear Factor ◽  
Glycogen Synthase Kinase 3Β ◽  
Inhibitory Protein ◽  
Cortical Astrocytes ◽  
Iκb Kinase ◽  
Gsk 3Β

ABSTRACT Recent studies have revealed a positive correlation between astrocyte apoptosis and rapid disease progression in persons with neurodegenerative diseases. Glycogen synthase kinase 3β (GSK-3β) is a molecular regulator of cell fate in the central nervous system and a target of the phosphatidylinositol 3-kinase (PI-3K) pathway. We have therefore examined the role of the PI-3K pathway, and of GSK-3β, in regulating astrocyte survival. Our studies indicate that inhibition of PI-3K leads to apoptosis in primary cortical astrocytes. Furthermore, overexpression of a constitutively active GSK-3β mutant (S9A) is sufficient to cause astrocyte apoptosis, whereas an enzymatically inactive GSK-3β mutant (K85M) has no effect. In light of reports on the interplay between GSK-3β and nuclear factor κB (NF-κB), and because of the antiapoptotic activity of NF-κB, we examined the effect of GSK-3β overexpression on NF-κB activation. These experiments revealed strong inhibition of NF-κB activation in astrocytes upon overexpression of the S9A, but not the K85M, mutant of GSK-3β. This was accompanied by stabilization of the NF-κB-inhibitory protein, IκBα and down-regulation of IκB kinase (IKK) activity. These findings therefore implicate GSK-3β as a regulator of NF-κB activation in astrocytes and suggest that the pro-apoptotic effects of GSK-3β may be mediated at least in part through the inhibition of NF-κB pathway.

scholarly journals Dextromethorphan Attenuates NADPH Oxidase-Regulated Glycogen Synthase Kinase 3β and NF-κB Activation and Reduces Nitric Oxide Production in Group A Streptococcal Infection

2018 ◽  
Vol 62 (6) ◽  
pp. e02045-17 ◽  
Author(s):  
Chia-Ling Chen ◽  
Miao-Huei Cheng ◽  
Chih-Feng Kuo ◽  
Yi-Lin Cheng ◽  
Ming-Han Li ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nadph Oxidase ◽  
Nuclear Translocation ◽  
Glycogen Synthase ◽  
Glycogen Synthase Kinase ◽  
Streptococcal Toxic Shock Syndrome ◽  
Glycogen Synthase Kinase 3Β ◽  
Diphenylene Iodonium ◽  
Group A ◽  
Gsk 3Β

ABSTRACTGroup AStreptococcus(GAS) is an important human pathogen that causes a wide spectrum of diseases, including necrotizing fasciitis and streptococcal toxic shock syndrome. Dextromethorphan (DM), an antitussive drug, has been demonstrated to efficiently reduce inflammatory responses, thereby contributing to an increased survival rate of GAS-infected mice. However, the anti-inflammatory mechanisms underlying DM treatment in GAS infection remain unclear. DM is known to exert neuroprotective effects through an NADPH oxidase-dependent regulated process. In the present study, membrane translocation of NADPH oxidase subunit p47phoxand subsequent reactive oxygen species (ROS) generation induced by GAS infection were significantly inhibited via DM treatment in RAW264.7 murine macrophage cells. Further determination of proinflammatory mediators revealed that DM effectively suppressed inducible nitric oxide synthase (iNOS) expression and NO, tumor necrosis factor alpha, and interleukin-6 generation in GAS-infected RAW264.7 cells as well as in air-pouch-infiltrating cells from GAS/DM-treated mice. GAS infection caused AKT dephosphorylation, glycogen synthase kinase-3β (GSK-3β) activation, and subsequent NF-κB nuclear translocation, which were also markedly inhibited by treatment with DM and an NADPH oxidase inhibitor, diphenylene iodonium. These results suggest that DM attenuates GAS infection-induced overactive inflammation by inhibiting NADPH oxidase-mediated ROS production that leads to downregulation of the GSK-3β/NF-κB/NO signaling pathway.

scholarly journals Nitric oxide induces tau hyperphosphorylation via glycogen synthase kinase-3β activation

FEBS Letters ◽  
2005 ◽  
Vol 579 (27) ◽  
pp. 6230-6236 ◽  
Author(s):  
Yong-Jie Zhang ◽  
Ya-Fei Xu ◽  
Ying-Hua Liu ◽  
Jun Yin ◽  
Jian-Zhi Wang
Keyword(s):  
Nitric Oxide ◽  
Glycogen Synthase ◽  
Glycogen Synthase Kinase ◽  
Tau Hyperphosphorylation ◽  
Glycogen Synthase Kinase 3Β
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