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Amyloid β‐Mediated Oxidative and Metabolic Stress in Rat Cortical Neurons: No Direct Evidence for a Role for H 2 O 2 Generation
Author(s) -
Zhang Zhiyuan,
Rydel Russell E.,
Drzewiecki Gary J.,
Fuson Kimberly,
Wright Sarah,
Wogulis Mark,
Audia James E.,
May Patrick C.,
Hyslop Paul A.
Publication year - 1996
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1996.67041595.x
Subject(s) - oxidative stress , neuroprotection , neurotoxicity , intracellular , pentose phosphate pathway , biochemistry , chemistry , reactive oxygen species , catalase , free radical scavenger , oxidative phosphorylation , citric acid cycle , superoxide dismutase , toxicity , biology , pharmacology , metabolism , glycolysis , organic chemistry
H 2 O 2 and free radical‐mediated oxidative stresses have been implicated in mediating amyloid β(1–40) [Aβ(1–40)] neurotoxicity to cultured neurons. In this study, we confirm that addition of the H 2 O 2 ‐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 H 2 O 2 . Aβ‐mediated elevation in intracellular H 2 O 2 production is suppressed by addition of a potent H 2 O 2 scavenger without any significant neuroprotection. Three intracellular biochemical markers of H 2 O 2 ‐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 H 2 O 2 generation in mediating Aβ toxicity, and we suggest that impairment of energy homeostasis may be a more significant early factor in the neurodegenerative process.