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Homocysteine potentiates β‐amyloid neurotoxicity: role of oxidative stress
Author(s) -
Ho Pei I.,
Collins Scott C.,
Dhitavat Sirikarnt,
Ortiz Daniela,
Ashline David,
Rogers Eugene,
Shea Thomas B.
Publication year - 2001
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.1471-4159.2001.00384.x
Subject(s) - oxidative stress , neurotoxicity , excitotoxicity , neurodegeneration , reactive oxygen species , chemistry , apoptosis , glutathione , neuroprotection , calcium , endocrinology , biochemistry , medicine , biology , programmed cell death , pharmacology , toxicity , disease , organic chemistry , enzyme
The cause of neuronal degeneration in Alzheimer's disease (AD) has not been completely clarified, but has been variously attributed to increases in cytosolic calcium and increased generation of reactive oxygen species (ROS). The β‐amyloid fragment (Aβ) of the amyloid precursor protein induces calcium influx, ROS and apoptosis. Homocysteine (HC), a neurotoxic amino acid that accumulates in neurological disorders including AD, also induces calcium influx and oxidative stress, which has been shown to enhance neuronal excitotoxicity, leading to apoptosis. We examined the possibility that HC may augment Aβ neurotoxicity. HC potentiated the Aβ‐induced increase in cytosolic calcium and apoptosis in differentiated SH‐SY‐5Y human neuroblastoma cells. The antioxidant vitamin E and the glutathione precursor N ‐acetyl‐ l ‐cysteine blocked apoptosis following cotreatment with HC and Aβ, indicating that apoptosis is associated with oxidative stress. These findings underscore that moderate accumulation of excitotoxins at concentrations that alone do not appear to initiate adverse events may enhance the effects of other factors known to cause neurodegeneration such as Aβ.