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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