Open AccessAzelnidipine Attenuates the Oxidative and NFκB Pathways in Amyloid-β-Stimulated Cerebral Endothelial Cells
Author(s) -
Tao Teng,
Devin M. Ridgley,
Andrey Tsoy,
Grace Y. Sun,
Sholpan Askarova,
James C.-M. Lee
Publication year - 2018
Publication title -
acs chemical neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.158
H-Index - 69
ISSN - 1948-7193
DOI - 10.1021/acschemneuro.8b00368
Subject(s) - oxidative stress , chemistry , calcium channel blocker , calcium channel , calcium , extracellular , voltage dependent calcium channel , l type calcium channel , channel blocker , calcium signaling , pharmacology , cerebral amyloid angiopathy , microbiology and biotechnology , medicine , biochemistry , signal transduction , biology , organic chemistry , dementia , disease
Cerebral amyloid angiopathy (CAA), a condition depicting cerebrovascular accumulation of amyloid β-peptide (Aβ), is a common pathological manifestation in Alzheimer's disease (AD). In this study, we investigated the effects of Azelnidipine (ALP), a dihydropyridine calcium channel blocker known for its treatment of hypertension, on oligomeric Aβ (oAβ)-induced calcium influx and its downstream pathway in immortalized mouse cerebral endothelial cells (bEND3). We found that ALP attenuated oAβ-induced calcium influx, superoxide anion production, and phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2) and calcium-dependent cytosolic phospholipase A 2 (cPLA 2 ). Both ALP and cPLA 2 inhibitor, methylarachidonyl fluorophosphate (MAFP), suppressed oAβ-induced translocation of NFκB p65 subunit to nuclei, suggesting that cPLA 2 activation and calcium influx are essential for oAβ-induced NFκB activation. In sum, our results suggest that calcium channel blocker could be a potential therapeutic strategy for suppressing oxidative stress and inflammatory responses in Aβ-stimulated microvasculature in AD.