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Abeta40, either soluble or aggregated, is a remarkably potent antioxidant in cell-free oxidative systems.
Biochemistry. 2009 May 26; 48(20):4354-70.B

Abstract

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.

Authors+Show Affiliations

Department of Chemistry, Gonda-Goldschmied Medical Research Center, Bar-Ilan University, Ramat-Gan 52900, Israel.No affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

19320465

Citation

Baruch-Suchodolsky, Rozena, and Bilha Fischer. "Abeta40, Either Soluble or Aggregated, Is a Remarkably Potent Antioxidant in Cell-free Oxidative Systems." Biochemistry, vol. 48, no. 20, 2009, pp. 4354-70.
Baruch-Suchodolsky R, Fischer B. Abeta40, either soluble or aggregated, is a remarkably potent antioxidant in cell-free oxidative systems. Biochemistry. 2009;48(20):4354-70.
Baruch-Suchodolsky, R., & Fischer, B. (2009). Abeta40, either soluble or aggregated, is a remarkably potent antioxidant in cell-free oxidative systems. Biochemistry, 48(20), 4354-70. https://doi.org/10.1021/bi802361k
Baruch-Suchodolsky R, Fischer B. Abeta40, Either Soluble or Aggregated, Is a Remarkably Potent Antioxidant in Cell-free Oxidative Systems. Biochemistry. 2009 May 26;48(20):4354-70. PubMed PMID: 19320465.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Abeta40, either soluble or aggregated, is a remarkably potent antioxidant in cell-free oxidative systems. AU - Baruch-Suchodolsky,Rozena, AU - Fischer,Bilha, PY - 2009/3/27/entrez PY - 2009/3/27/pubmed PY - 2009/6/20/medline SP - 4354 EP - 70 JF - Biochemistry JO - Biochemistry VL - 48 IS - 20 N2 - 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. SN - 1520-4995 UR - https://www.unboundmedicine.com/medline/citation/19320465/Abeta40_either_soluble_or_aggregated_is_a_remarkably_potent_antioxidant_in_cell_free_oxidative_systems_ L2 - https://dx.doi.org/10.1021/bi802361k DB - PRIME DP - Unbound Medicine ER -