کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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330618 | 1433670 | 2006 | 11 صفحه PDF | دانلود رایگان |
The reduced antioxidant defense in apolipoprotein E ɛ4/ɛ4 carriers may contribute to β-amyloidosis. Previously we found that Fe2+-induced oxidative stress caused greater protein oxidation in ɛ4/ɛ4 than in ɛ3/ɛ3 human brain vascular smooth muscle cells. Moreover, Fe2+ induced lysosomal accumulation of endogenous Aβ and APOE in cultured cells, and Aβ deposition in vascular tunica media in organotypic cultures of brain vessels.Here we demonstrated that Fe2+ enhanced an uptake of exogenous Aβ 1–40 and its deposition together with APOE in lysosomes in myocytes. Aβ deposits were associated with lipid-peroxidation and protein ubiquitination, and were more abundant and stable in ɛ4/ɛ4 than in ɛ3/ɛ3 cells. In organotypic cultures of brain vessels Fe2+ induced deposition of non-fibrillar and fibrillar Aβ 1–40 in vascular tunica media.We hypothesize that locally increased concentrations of iron induce accumulation of exogenous and endogenous Aβ in SMCs, triggering β-amyloid angiopathy. The greater susceptibility of ɛ4 carriers to Fe2+ ions may result in an increased risk of β-amyloidosis.
Journal: Neurobiology of Aging - Volume 27, Issue 6, June 2006, Pages 804–814