Glucocorticoids exacerbate peroxynitrite mediated potentiation of glucose deprivation-induced death of rat primary astrocytes

Chan Young Shin, Ji Woong Choi, Eun Sook Jang, Jong Hoon Ryu, Won Ki Kim, Hyoung Chun Kim, Kwang Ho Ko

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Glucocorticoids have been implicated in the exacerbation of several types of neurotoxicity in various neuropathological situations. In this study, we investigated the effect of a glucocorticoid dexamethasone on glucose deprivation induced cell death of immunostimulated rat primary astrocytes, which is dependent on the production of peroxynitrite from the immunostimulated cells [Choi et al. Glia, 31(2001) 155-164; J. Neuroimmunol. 112 (2001) 55-62]. Glucose deprivation in immunostimulated rat primary astrocytes results in the release of lactate dehydrogenase (LDH) after 5 h and co-treatment with dexamethasone (1-1000 nM) dose-dependently increased LDH release. Treatment of the exogenous peroxynitrite generator SIN-1 (20 μM), plus glucose deprivation, also increased LDH release after 6 h and co-treatment with dexamethasone dose-dependently increased LDH release. A glucocorticoid receptor antagonist, RU-486, reversed the potentiation of cell death by dexamethasone. Glucose deprivation in immunostimulated cells decreased the intracellular ATP levels, which preceded LDH release from the cell, and co-treatment with dexamethasone dose-dependently potentiated the depletion of intracellular ATP levels. In addition, dexamethasone further deteriorated SIN-1 plus glucose deprivation-induced decrease in mitochondrial transmembrane potential in rat primary astrocytes, which was reversed by RU-486. The results from the present study suggest that glucocorticoids may be detrimental to astrocytes in situations where activation of glial cells are observed, including ischemia and Alzheimer's disease, by mechanisms involving depletion of intracellular ATP levels and deterioration of mitochondrial transmembrane potentials.

Original languageEnglish
Pages (from-to)163-171
Number of pages9
JournalBrain Research
Volume923
Issue number1-2
DOIs
Publication statusPublished - 2001 Dec 27

Keywords

  • ATP
  • Astrocyte
  • Dexamethasone
  • Glucose-deprivation
  • Mitochondrial transmembrane potential
  • Peroxynitrite

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

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