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Antioxid Redox Signal. 2011 Jun 15;14(12):2385-97. doi: 10.1089/ars.2010.3681. Epub 2011 Mar 28.

Astrocytic redox remodeling by amyloid beta peptide.

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1
Department of Biochemistry, University of Michigan Medical School, Ann Arbor, MI 48109, USA.

Abstract

Astrocytes are critical for neuronal redox homeostasis providing them with cysteine needed for glutathione synthesis. In this study, we demonstrate that the astrocytic redox response signature provoked by amyloid beta (Aβ) is distinct from that of a general oxidant (tertiary-butylhydroperoxide [t-BuOOH]). Acute Aβ treatment increased cystathionine β-synthase (CBS) levels and enhanced transsulfuration flux in contrast to repeated Aβ exposure, which decreased CBS and catalase protein levels. Although t-BuOOH also increased transsulfuration flux, CBS levels were unaffected. The net effect of Aβ treatment was an oxidative shift in the intracellular glutathione/glutathione disulfide redox potential in contrast to a reductive shift in response to peroxide. In the extracellular compartment, Aβ, but not t-BuOOH, enhanced cystine uptake and cysteine accumulation, and resulted in remodeling of the extracellular cysteine/cystine redox potential in the reductive direction. The redox changes elicited by Aβ but not peroxide were associated with enhanced DNA synthesis. CBS activity and protein levels tended to be lower in cerebellum from patients with Alzheimer's disease than in age-matched controls. Our study suggests that the alterations in astrocytic redox status could compromise the neuroprotective potential of astrocytes and may be a potential new target for therapeutic intervention in Alzheimer's disease.

PMID:
21235355
PMCID:
PMC3096517
DOI:
10.1089/ars.2010.3681
[Indexed for MEDLINE]
Free PMC Article
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