| First Author | Muche A | Year | 2017 |
| Journal | PLoS One | Volume | 12 |
| Issue | 6 | Pages | e0178127 |
| PubMed ID | 28617802 | Mgi Jnum | J:247325 |
| Mgi Id | MGI:5915102 | Doi | 10.1371/journal.pone.0178127 |
| Citation | Muche A, et al. (2017) Oxidative stress affects processing of amyloid precursor protein in vascular endothelial cells. PLoS One 12(6):e0178127 |
| abstractText | BACKGROUND: Oxidative stress is thought to be a key player in the pathogenesis of neurodegenerative dementia, including Alzheimer's disease (AD). It has been assumed that oxidative stress contributes to the ss-amyloid deposition in cerebral blood vessels. METHODS: In order to prove this hypothesis, we examined the effect of oxidative stress on the processing of amyloid precursor protein (APP) in primary endothelial cells (EC) derived from cerebral cortical tissue of transgenic Tg2576 mice. Following exposure of EC by 1 muM hydrogen peroxide for up to 48 hours, formation and secretion of APP cleavage products sAPPalpha and sAPPss into the culture medium as well as the expression of endothelial APP were assessed. RESULTS: Oxidative stress resulted in enhanced secretion of sAPPss into the culture medium as compared to controls (absence of hydrogen peroxide), which was accompanied by an increased APP expression, induction of VEGF synthesis, nitric oxide and oxygen free radicals productions, and differential changes of endothelial phospo-p42/44 MAPK expression. CONCLUSION: The data suggest that oxidative stress may represent a major risk factor in causing Ass deposition in the brain vascular system by initiating the amyloidogenic route of endothelial APP processing. The enhanced beta-secretase activity following oxidative stress exposure, possibly promoted by phosphorylation of p42/44 MAPK. |
