Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8322470 | The International Journal of Biochemistry & Cell Biology | 2015 | 10 Pages |
Abstract
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.
Keywords
HIF1post nuclear supernatantRFUPSEN1DPHGangliosidesRBE4Presenilin-1BSSMEFsFBSOGDECLPMSFBACE1Aβ(AD)sphingomyelinenhanced chemiluminescenceAlzheimer's diseaseCNSfetal bovine serumbrain endothelial cellscentral nervous systemAqueous phaseOrganic phasephosphatidylinositolphosphatidylcholinephosphatidylethanolaminePhosphatidylserinePhospholipidsphenylmethylsulphonyl fluorideOxygen and glucose deprivationbalanced salt solutionRelative Fluorescence UnitsAmyloid precursor protein (APP)amyloid peptidePNScholesterol
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Authors
Anna Brambilla, Elena Lonati, Chiara Milani, Angela Maria Rizzo, Francesca Farina, Laura Botto, Massimo Masserini, Paola Palestini, Alessandra Bulbarelli,