Linked Life Data

19320465

Source:http://linkedlifedata.com/resource/pubmed/id/19320465

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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
20
pubmed:dateCreated
2009-5-19
pubmed:abstractText
The brains of individuals diagnosed with Alzheimer's disease (AD) are characterized by amyloid plaques, of which the major component is Abeta peptide. Excessive Cu and Fe ions binding to Abeta were suggested to have a deleterious effect on promoting both the aggregation of Abeta and the generation of reactive oxygen species (ROS). Other studies suggested that Abeta plays a protective role by acting as an antioxidant at nanomolar concentrations. The apparent confusion regarding the antioxidant and pro-oxidant properties of Abeta(40) encouraged us to explore the modulatory role of Abeta(40) at the molecular level under oxidative stress conditions. Here, we focused on Abeta(40) in the simplest oxidative system, namely, Cu(I)/Cu(II)/Fe(II)-H(2)O(2). Using ESR, we monitored the production of OH radicals in the above-mentioned systems in the presence of Abeta(40). We found that Abeta(40), either in its soluble or in its aggregated form, functioned as a remarkably potent antioxidant in Cu(I)/Fe(II)-catalyzed radical-producing systems and slightly less potently in the presence of Cu(II) with IC(50) values of 13-62 muM. Abeta(40) proved to be 3.8-6.5 and 15-42 times more potent than the soluble Abeta(28) and the potent antioxidant Trolox, respectively, in the Cu(I)/Fe(II)-H(2)O(2) systems. Time-dependent enhancement of ROS production by Abeta(40) occurs only at low concentrations of aggregated Abeta(40) and in the presence of Cu(II). On the basis of the extremely low IC(50) values of Abeta(40) and the extensive oxidative damage caused to Abeta(40) in Cu(I)/Fe(II)-H(2)O(2) systems, we propose that radical scavenging is the major mechanism of antioxidant activity of Abeta(40) in addition to metal ion chelation. In summary, Abeta(40), either soluble or aggregated, at either nanomolar or micromolar concentrations is a highly potent antioxidant in cell-free oxidative systems, acting mainly as a radical scavenger. Therefore, we propose that it is not the Abeta(40)-Cu(I)/Fe(II) complex per se that is responsible for the oxidative damage in AD.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
1520-4995
pubmed:author
pubmed:issnType
Electronic
pubmed:day
26
pubmed:volume
48
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4354-70
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
Abeta40, either soluble or aggregated, is a remarkably potent antioxidant in cell-free oxidative systems.
pubmed:affiliation
Department of Chemistry, Gonda-Goldschmied Medical Research Center, Bar-Ilan University, Ramat-Gan 52900, Israel.
pubmed:publicationType
Journal Article