Glucose Deprivation Increases Hydrogen Peroxide Level in Immunostimulated Rat Primary Astrocytes

Ji Woong Choi, Chan Young Shin, Byoung Kwon Yoo, Min Sik Choi, Woo Jong Lee, Byoung Hee Han, Won Ki Kim, Hyoung Chun Kim, Kwang Ho Ko

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15 Citations (Scopus)

Abstract

Activated astrocytes produce a large amount of bioactive molecules, including reactive oxygen and nitrogen species. Astrocytes are in general resistant to those reactive species. However, we previously reported that immunostimulated astrocytes became highly vulnerable to metabolic insults, such as glucose deprivation. In this study, we investigated whether H 2O2 production was associated with the increased vulnerability. Glucose deprivation for up to 8 hr did not change the intracellular level of H2O2 in astrocytes. Treatment with lipopolysaccharide plus interferon-γ for 48 hr evoked astroglial H 2O2 production; however, no apparent death or injury was observed in immunostimulated astrocytes. Glucose deprivation after 48 hr of immunostimulation markedly increased H2O2 level, depleted adenosine triphosphate (ATP), and enhanced lactate dehydrogenase (LDH) release. The ATP depletion and LDH release were in part prevented by catalase, mannitol, and N-acetyl-L-cysteine. The enhanced level of H2O2 in glucose-deprived immunostimulated astrocytes appeared to be secondary to the depletion of reduced glutathione. 4-(2-Aminoethyl)bebzenesulfonyl fluoride (AEBSF), an inhibitor of NADPH oxidase, reduced H2O2 level and LDH release in glucose-deprived immunostimulated astrocytes. H 2O2, either endogenously produced or exogenously added, depolarized mitochondrial transmembrane potential in glucose-deprived astrocytes, leading to their ATP depletion and death. The present results strongly indicate that glucose deprivation causes deterioration of immunostimulated astrocytes by increasing the intracellular concentration of H2O2.

Original languageEnglish
Pages (from-to)722-731
Number of pages10
JournalJournal of Neuroscience Research
Volume75
Issue number5
DOIs
Publication statusPublished - 2004 Mar 1
Externally publishedYes

Keywords

  • ATP
  • Glucose deprivation
  • HO
  • Immunostimulation
  • Rat primary astrocyte

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

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    Choi, J. W., Shin, C. Y., Yoo, B. K., Choi, M. S., Lee, W. J., Han, B. H., Kim, W. K., Kim, H. C., & Ko, K. H. (2004). Glucose Deprivation Increases Hydrogen Peroxide Level in Immunostimulated Rat Primary Astrocytes. Journal of Neuroscience Research, 75(5), 722-731. https://doi.org/10.1002/jnr.20009