Aspirin-induced blockade of NF-kappaB activity restrains up-regulation of glial fibrillary acidic protein in human astroglial cells

Biochimica Et Biophysica Acta
Moon-Kyoung BaeSoo-Kyung Bae

Abstract

The marked induction of glial fibrillary acidic protein (GFAP) has been observed in astrocytes during neuropathological processes accompanying reactive gliosis; however, the precise molecular mechanism(s) underlying this GFAP induction remains poorly resolved. Therefore, in this study, we examined whether the change of nuclear factor-kappa B (NF-kappaB) activity can influence GFAP expression levels. Aspirin, widely used to prevent NF-kappaB activity, reduced the levels of GFAP mRNA and protein in human astroglial cells including human glioblastoma A172 cells and primary human brain astrocyte cells (HBAs). Furthermore, aspirin inhibited the effects of hypoxic injury on the up-regulation of GFAP expression in HBAs. We confirmed the repressive effect of aspirin on GFAP transcription by GFAP promoter-driven reporter assay and found that one NF-kappaB binding site conserved in the mouse and human GFAP gene promoters is critical for this effect. To further delineate whether NF-kappaB is directly involved in the regulation of GFAP gene expression, we transfected A172 cells with an expression vector encoding a super-repressor IkappaBalpha protein (IkappaBalpha-SR) to specifically inhibit NF-kappaB activity and found the marked reductio...Continue Reading

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Citations

Oct 1, 2010·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Mary E Hamby, Michael V Sofroniew
Feb 4, 2014·Cell Death and Differentiation·A TchoghandjianS Fulda
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Jul 26, 2015·Progress in Retinal and Eye Research·J Carlos PastorSantiago Delgado-Tirado
Jul 18, 2016·Neuroscience·Amita Daverey, Sandeep K Agrawal
Jan 25, 2014·Neuroscience Letters·Anna Maria ColangeloMichele Papa
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Mar 13, 2014·Neuropathology and Applied Neurobiology·Anna-Eva BlankMichel Mittelbronn
Feb 20, 2021·ASN Neuro·Michael Brenner, Albee Messing
May 15, 2007·Experimental Cell Research·Roy A QuinlanAlbee Messing

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