Geldanamycin provides posttreatment protection against glutamate- induced oxidative toxicity in a mouse hippocampal cell line

Nianqing Xiao, Clifton W. Callaway, Christopher A. Lipinski, Shawn D. Hicks, Donald B. DeFranco

Research output: Contribution to journalArticle

47 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)95-101
Number of pages7
JournalJournal of Neurochemistry
Volume72
Issue number1
DOIs
StatePublished - 1999
Externally publishedYes

Fingerprint

Toxicity
Glutamic Acid
Cells
Cell Line
Proto-Oncogene Proteins c-raf
Rifabutin
Cell signaling
HSP90 Heat-Shock Proteins
Anabolic Agents
DNA Cleavage
Oxidative stress
Cell death
Heat-Shock Proteins
Antineoplastic Agents
Glutathione
geldanamycin
Oxidative Stress
Cell Death
Degradation
DNA

Keywords

  • Geldanamycin
  • Heat shock proteins
  • Oxidative toxicity

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

Geldanamycin provides posttreatment protection against glutamate- induced oxidative toxicity in a mouse hippocampal cell line. / Xiao, Nianqing; Callaway, Clifton W.; Lipinski, Christopher A.; Hicks, Shawn D.; DeFranco, Donald B.

In: Journal of Neurochemistry, Vol. 72, No. 1, 1999, p. 95-101.

Research output: Contribution to journalArticle

Xiao, Nianqing ; Callaway, Clifton W. ; Lipinski, Christopher A. ; Hicks, Shawn D. ; DeFranco, Donald B. / Geldanamycin provides posttreatment protection against glutamate- induced oxidative toxicity in a mouse hippocampal cell line. In: Journal of Neurochemistry. 1999 ; Vol. 72, No. 1. pp. 95-101.
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