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Alzheimer’s amyloid beta protein promotes CYP epoxygenase dependent generation of superoxide
Author(s) -
Gebremedhin Debebe,
Riley Desiry,
Narayanan Jaya,
Harder David
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a733-c
Subject(s) - epoxygenase , superoxide , chemistry , oxidative stress , amyloid beta , neuroprotection , alzheimer's disease , amyloid (mycology) , medicine , pharmacology , endocrinology , cytochrome p450 , biochemistry , biology , enzyme , disease , peptide , inorganic chemistry
Alzheimer’s disease, a common cause of dementia, is primarily tied to the formation of senile plaques consisting of deposition of the amyloid beta (Aβ) protein. Aβ has been implicated as a molecular link between oxidative stress and neuronal death in this disease state. Although the mechanism remains unclear, Aβ is known to induce free radical generation. In the present study, we chose to examine the enzyme cytochrome P450 (CYP) epoxygenase as a possible pathway for the generation of superoxide induced by Aβ protein. Using the superoxide detection probe hydroethidine and the recently developed fluorescence HPLC assay, we found that inhibition of CYP epoxygenase activity reduces the production of superoxide stimulated with the Aβ protein in rat brain astrocytes, and that evoked by alpha adrenergic receptor activation in tissues of Alzheimer’s patient brain. Antioxidant pretreatment attenuated the Aβ protein and alpha adrenergic stimulation induced generation of superoxide. These findings suggest that the CYP epoxygenase mediates Aβ and alpha adrenergic receptor activation stimulated superoxide production and could be a possible therapeutic target for lowering free radical level in Alzheimer’s disease.