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Glucose deprivation increases hydrogen peroxide level in immunostimulated rat primary astrocytes
Author(s) -
Choi Ji Woong,
Shin Chan Young,
Yoo Byoung Kwon,
Choi Min Sik,
Lee Woo Jong,
Han Byoung Hee,
Kim WonKi,
Kim HyoungChun,
Ko Kwang Ho
Publication year - 2004
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.20009
Subject(s) - hydrogen peroxide , primary (astronomy) , chemistry , astrocyte , biochemistry , microbiology and biotechnology , endocrinology , medicine , biology , central nervous system , physics , astronomy
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 2 O 2 production was associated with the increased vulnerability. Glucose deprivation for up to 8 hr did not change the intracellular level of H 2 O 2 in astrocytes. Treatment with lipopolysaccharide plus interferon‐γ for 48 hr evoked astroglial H 2 O 2 production; however, no apparent death or injury was observed in immunostimulated astrocytes. Glucose deprivation after 48 hr of immunostimulation markedly increased H 2 O 2 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 H 2 O 2 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 H 2 O 2 level and LDH release in glucose‐deprived immunostimulated astrocytes. H 2 O 2 , 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 H 2 O 2 . © 2004 Wiley‐Liss, Inc.