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Formation of amyloid-β oligomers in brain vascular smooth muscle cells transiently exposed to iron-induced oxidative stress

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Abstract

Vascular smooth muscle cells are involved in deposition of amyloid in brain blood vessels. Accumulation of amyloid-β peptide (Aβ) in cultured brain vascular smooth muscle cells that overexpress human amyloid-β precursor protein (APP) Swedish, is strongly enhanced by exposure to iron ions. We studied cellular accumulation of Aβ and APP processing in vascular smooth muscle cells during recovery after exposure to ferrous ions using cells cultured from Tg2576 mice. The treatment with ferrous ions for 24 and 48 h significantly increased the intracellular levels of ferric, but not ferrous iron. The treatment led to cellular accumulation of C-terminal fragments of APP and to a decreased secretion of APP, Aβ1–40, and Aβ1–42, all of which were quickly normalized in iron-free culture conditions. These effects of iron were neutralized by α-tocopherol, suggesting the role of oxygen reactive species in altered APP processing. Formation of abundant Aβ oligomers, mainly Aβ1–40 tetramers and pentamers, were detected in iron-treated cells, particularly during subsequent culture in iron-free media for up to 72 h. The data suggest that transient increases in local availability of iron in brain blood vessel walls in vivo, e.g., after microhemorhages, may trigger Aβ oligomerization.

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Acknowledgments

We thank Dr. Pankaj Mehta (IBRDD, Staten Island, NY) for antibody R57, and Dr. Thomas August and Developmental Studies Hybridoma Bank (University of Iowa, IA) for mAb LAMP-1, developed under the auspices of the NICHD and maintained by the University of Iowa, Department of Biological Sciences (Iowa City, IA 52242). This study was supported with funds from the New York State Office of Mental Retardation and Developmental Disabilities.

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    Janusz Frackowiak, Anna Potempska & Bozena Mazur-Kolecka

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Frackowiak, J., Potempska, A. & Mazur-Kolecka, B. Formation of amyloid-β oligomers in brain vascular smooth muscle cells transiently exposed to iron-induced oxidative stress. Acta Neuropathol 117, 557–567 (2009). https://doi.org/10.1007/s00401-009-0497-0

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