Amyloid β-mediated oxidative and metabolic stress in rat cortical neurons: No direct evidence for a role for H2O2 generation

Zhiyuan Zhang, Russell E. Rydel, Gary J. Drzewiecki, Kimberly Fuson, Sarah Wright, Mark Wogulis, James E. Audia, Patrick C. May, Paul A. Hyslop

Research output: Contribution to journalArticle

64 Scopus citations

Abstract

H2O2 and free radical-mediated oxidative stresses have been implicated in mediating amyloid β(140) [Aβ(1-40)] neurotoxicity to cultured neurons. In this study, we confirm that addition of the H2O2-scavenging enzyme catalase protects neurons in culture against Aβ-mediated toxicity; however, it does so by a mechanism that does not involve its ability to scavenge H2O2. Aβ-mediated elevation in intracellular H2O2 production is suppressed by addition of a potent H2O2 scavenger without any significant neuroprotection. Three intracellular biochemical markers of H2O2-mediated oxidative stress were unchanged by Aβ treatment: (a) glyceraldehyde-3- phosphate dehydrogenase activity, (b) hexose monophosphate shunt activity, and (c) glucose oxidation via the tricarboxylic acid cycle. Ionspray mass spectra of Aβ in the incubation medium indicated that Aβ itself is an unlikely source of reactive oxygen species. In this study we demonstrate that intracellular ATP concentration is compromised during the first 24-h exposure of neurons to Aβ. Our results challenge a pivotal role for H2O2 generation in mediating Aβ toxicity, and we suggest that impairment of energy homeostasis may be a more significant early factor in the neurodegenerative process.

Original languageEnglish (US)
Pages (from-to)1595-1606
Number of pages12
JournalJournal of Neurochemistry
Volume67
Issue number4
StatePublished - Oct 1996
Externally publishedYes

Keywords

  • Alzheimer's disease
  • Amyloid β
  • ATP
  • Cortical neurons
  • Oxidative injury

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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    Zhang, Z., Rydel, R. E., Drzewiecki, G. J., Fuson, K., Wright, S., Wogulis, M., Audia, J. E., May, P. C., & Hyslop, P. A. (1996). Amyloid β-mediated oxidative and metabolic stress in rat cortical neurons: No direct evidence for a role for H2O2 generation. Journal of Neurochemistry, 67(4), 1595-1606.