Abbreviations used : GA, geldanamycin ; GSH, glutathione ; hsp70, heat shock protein 70 ; hsp90, heat shock protein 90 ; 12-LOX, 12-lipoxygenase ; MTT, 3-(4,5-dimethyldiazol-2-yl)-2,5-diphenyltetrazolium bromide ; ROS, reactive oxygen species.
Geldanamycin Provides Posttreatment Protection Against Glutamate-Induced Oxidative Toxicity in a Mouse Hippocampal Cell Line
Article first published online: 18 JAN 2002
Journal of Neurochemistry
Volume 72, Issue 1, pages 95–101, January 1999
How to Cite
Xiao, N., Callaway, C. W., Lipinski, C. A., Hicks, S. D. and DeFranco, D. B. (1999), Geldanamycin Provides Posttreatment Protection Against Glutamate-Induced Oxidative Toxicity in a Mouse Hippocampal Cell Line. Journal of Neurochemistry, 72: 95–101. doi: 10.1046/j.1471-4159.1999.0720095.x
- Issue published online: 18 JAN 2002
- Article first published online: 18 JAN 2002
- Heat shock proteins;
- Oxidative toxicity
Abstract : The benzoquinoid ansamycin geldanamycin interferes with many cell signaling pathways and is currently being evaluated as an anticancer agent. The main intracellular target of geldanamycin is the 90-kDa heat shock protein, hsp90. In this report we demonstrate that geldanamycin is effective at preventing glutamate-induced oxidative toxicity in the HT22 mouse hippocampal cell line, even if given 4 h after glutamate treatment. Geldanamycin prevents glutamate-induced internucleosomal DNA cleavage in the HT22 cells but does not reverse the depletion of glutathione levels brought about by glutamate treatment. Both anabolic and catabolic effects are generated by geldanamycin treatment of HT22 cells, as evidenced by the induction of hsp70 expression and degradation of c-Raf-1 protein, respectively. Thus, geldanamycin may provide an effective strategy for manipulating signaling pathways in neuronal cells that use hsp90 as they proceed through a programmed cell death pathway in response to oxidative stress.