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 H. 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
Externally publishedYes

Fingerprint

Peroxynitrous Acid
Astrocytes
Dexamethasone
Glucocorticoids
L-Lactate Dehydrogenase
Glucose
Mifepristone
Adenosine Triphosphate
Neuroglia
Membrane Potentials
Cell Death
Glucocorticoid Receptors
Alzheimer Disease
Ischemia

Keywords

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

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Glucocorticoids exacerbate peroxynitrite mediated potentiation of glucose deprivation-induced death of rat primary astrocytes. / Shin, Chan Young; Choi, Ji Woong; Jang, Eun Sook; Ryu, Jong Hoon; Kim, Won-Ki; Kim, Hyoung Chun; Ko, Kwang H.

In: Brain Research, Vol. 923, No. 1-2, 27.12.2001, p. 163-171.

Research output: Contribution to journalArticle

Shin, Chan Young ; Choi, Ji Woong ; Jang, Eun Sook ; Ryu, Jong Hoon ; Kim, Won-Ki ; Kim, Hyoung Chun ; Ko, Kwang H. / Glucocorticoids exacerbate peroxynitrite mediated potentiation of glucose deprivation-induced death of rat primary astrocytes. In: Brain Research. 2001 ; Vol. 923, No. 1-2. pp. 163-171.
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