کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
8322470 1539875 2015 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Ischemic conditions and β-secretase activation: The impact of membrane cholesterol enrichment as triggering factor in rat brain endothelial cells
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
Ischemic conditions and β-secretase activation: The impact of membrane cholesterol enrichment as triggering factor in rat brain endothelial cells
چکیده انگلیسی
Using brain microvascular endothelial cells, here we demonstrate how oxygen and glucose deprivation followed by normal conditions restoration, mimicking ischemic environment, increases cell cholesterol amount (+20%), reduces membrane fluidity and results in strong activation (+40%) of β-secretase 1 enzymatic activity. Moreover, we observed an increase of amyloid precursor protein and β-secretase 1 protein levels with altered localization in non-discrete (Triton X-100 soluble) membrane domains, leading to an enhanced production of amyloid precursor protein β-carboxyl-terminal fragment. Therefore, lipid alterations induced by oxygen and glucose deprivation enhance β-secretase 1 activity, favor its proximity to amyloid precursor protein and may concur to increased amyloidogenic cleavage. The latter, represents a detrimental event that may contribute to β-amyloid homeostasis impairment in the brain and to Alzheimer's disease-related BBB dysfunctions.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: The International Journal of Biochemistry & Cell Biology - Volume 69, December 2015, Pages 95-104
نویسندگان
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