title: Oxidative stress induces apoptosis in C6 glioma cells: involvement of mitogen-activated protein kinases and nuclear factor kappa B.
abstract: Excessive oxidative stress has been implicated in the induction of cell death in a variety of neurodegenerative diseases. In the present study, hydrogen peroxide (H2O2)-induced cell death in rat C6 glioma cells was used as a model system for studying the molecular events associated with oxidative stress-induced cell death in glial cells. We demonstrate that exposure of C6 glioma cells to H2O2 results in apoptotic cell death in a concentration-dependent manner, and caused activation of a member of the caspase-3-like family of proteases resulting in cleavage of the DNA repair enzyme poly(ADP-ribose)polymerase, PARP. Furthermore, H2O2 induced a transient activation of the transcription factor, nuclear factor kappa B (NF(Kappa)B). Pre-treatment of cells with the antioxidant N-acetylcysteine, (NAC), prevented both the activation of NF(Kappa)B and the induction of apoptosis by H2O2, suggesting a possible role for this transcription factor in oxidant-induced apoptosis in glial cells. Exposure of the cells to H2O2 led to transient activation of both c-Jun N-terminal kinase (JNK) and p38 kinase but has no effect on extracellular regulated kinase (ERK) activity. Inhibition of p38 by SB203580 did not protect the cells against H2O2-induced apoptosis suggesting that activation of p38 is not essential for H2O2-mediated cell death in C6 glioma cells.
authors.affiliation: Department of Biochemistry, Trinity College Dublin, Ireland.
authors.forename: M
authors.initials: M
authors.lastname: Marangolo
authors.forename: M M
authors.initials: MM
authors.lastname: McGee
authors.forename: K F
authors.initials: KF
authors.lastname: Tipton
authors.forename: D C
authors.initials: DC
authors.lastname: Williams
authors.forename: D M
authors.initials: DM
authors.lastname: Zisterer