These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Glycogen synthase kinase 3beta-mediated apoptosis of primary cortical astrocytes involves inhibition of nuclear factor kappaB signaling.
    Author: Sanchez JF, Sniderhan LF, Williamson AL, Fan S, Chakraborty-Sett S, Maggirwar SB.
    Journal: Mol Cell Biol; 2003 Jul; 23(13):4649-62. PubMed ID: 12808104.
    Abstract:
    Recent studies have revealed a positive correlation between astrocyte apoptosis and rapid disease progression in persons with neurodegenerative diseases. Glycogen synthase kinase 3beta (GSK-3beta) 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-3beta, 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-3beta mutant (S9A) is sufficient to cause astrocyte apoptosis, whereas an enzymatically inactive GSK-3beta mutant (K85M) has no effect. In light of reports on the interplay between GSK-3beta and nuclear factor kappaB (NF-kappaB), and because of the antiapoptotic activity of NF-kappaB, we examined the effect of GSK-3beta overexpression on NF-kappaB activation. These experiments revealed strong inhibition of NF-kappaB activation in astrocytes upon overexpression of the S9A, but not the K85M, mutant of GSK-3beta. This was accompanied by stabilization of the NF-kappaB-inhibitory protein, IkappaBalpha and down-regulation of IkappaB kinase (IKK) activity. These findings therefore implicate GSK-3beta as a regulator of NF-kappaB activation in astrocytes and suggest that the pro-apoptotic effects of GSK-3beta may be mediated at least in part through the inhibition of NF-kappaB pathway.
    [Abstract] [Full Text] [Related] [New Search]