Synergistic depletion of astrocytic glutathione by glucose deprivation and peroxynitrite

Correlation with mitochondrial dysfunction and subsequent cell death

Chung Ju, Keum Na Yoon, Yu Kyoung Oh, Hyoung Chun Kim, Chan Young Shin, Jae Ryun Ryu, Kwang Ho Ko, Won-Ki Kim

Research output: Contribution to journalArticle

47 Citations (Scopus)

Abstract

Previously we reported that immunostimulated astrocytes were highly vulnerable to glucose deprivation. The augmented death was mimicked by the peroxynitrite (ONOO-)-producing reagent 3-morpholinosydnonimine (SIN-1). Here we show that glucose deprivation and ONOO- synergistically deplete intracellular reduced glutathione (GSH) and augment the death of astrocytes via formation of cyclosporin A-sensitive mitochondrial permeability transition (MPT) pore. Astrocytic GSH levels were only slightly decreased by glucose deprivation or SIN-1 (200 μM) alone. In contrast, a rapid and large depletion of GSH was observed in glucose-deprived/SIN-1 -treated astrocytes. The depletion of GSH occurred before a significant release of lactate dehydrogenase (a marker of cell death). Superoxide dismutase and ONOO- scavengers completely blocked the augmented death, indicating that the reaction of nitric oxide with superoxide to form ONOO- was implicated. Furthermore, nitrotyrosine immunoreactivity (a marker Of ONOO-) was markedly enhanced in glucose-deprived/SIN-1-treated astrocytes. Mitochondrial transmembrane potential (MTP) was synergistically decreased in glucose- deprived/SIN-1-treated astrocytes. The glutathione synthase inhibitor L- buthionine-(S,R)-sulfoximine markedly decreased the MTP and increased lactate dehydrogenase (LDH) releases in SIN-1-treated astrocytes. Cyclosporin A, an MPT pore blocker, completely prevented the MTP depolarization as well as the enhanced LDH releases in glucose-deprived/SIN-1-treated astrocytes.

Original languageEnglish
Pages (from-to)1989-1998
Number of pages10
JournalJournal of Neurochemistry
Volume74
Issue number5
DOIs
Publication statusPublished - 2000 May 3
Externally publishedYes

Fingerprint

Peroxynitrous Acid
Cell death
Astrocytes
Glutathione
Cell Death
Glucose
L-Lactate Dehydrogenase
Membrane Potentials
Cyclosporine
Glutathione Synthase
Depolarization
Superoxides
Superoxide Dismutase
Nitric Oxide

Keywords

  • Astrocyte
  • Glucose deprivation
  • Glutathione
  • Mitochondrial transmembrane potential
  • Nitric oxide
  • Peroxynitrite

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

Synergistic depletion of astrocytic glutathione by glucose deprivation and peroxynitrite : Correlation with mitochondrial dysfunction and subsequent cell death. / Ju, Chung; Yoon, Keum Na; Oh, Yu Kyoung; Kim, Hyoung Chun; Shin, Chan Young; Ryu, Jae Ryun; Ko, Kwang Ho; Kim, Won-Ki.

In: Journal of Neurochemistry, Vol. 74, No. 5, 03.05.2000, p. 1989-1998.

Research output: Contribution to journalArticle

Ju, Chung ; Yoon, Keum Na ; Oh, Yu Kyoung ; Kim, Hyoung Chun ; Shin, Chan Young ; Ryu, Jae Ryun ; Ko, Kwang Ho ; Kim, Won-Ki. / Synergistic depletion of astrocytic glutathione by glucose deprivation and peroxynitrite : Correlation with mitochondrial dysfunction and subsequent cell death. In: Journal of Neurochemistry. 2000 ; Vol. 74, No. 5. pp. 1989-1998.
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