期刊
ENVIRONMENTAL POLLUTION
卷 246, 期 -, 页码 763-771出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.envpol.2018.12.080
关键词
Black carbon; Alzheimer's disease; p-Tau; Amyloid-beta; Autophagy
资金
- Joint NSFC-ISF Research Program - National Natural Science Foundation of China
- Israel Science Foundation [41561144007]
- National Natural Science Foundation of China [91543123, 81771303, 41877371]
- Innovative Research Team in University [IRT13078]
- Shanghai Pujiang Program [17PJ1411000]
Ambient ultrafine black carbon (uBC) can potentially cross blood-brain barrier, however, very little is currently known about the effects they may have on central nervous system. This study aimed to explore the roles of autophagy in Alzheimer-like pathogenic changes promoted by uBC in SH-SY5Y cells. We firstly found uBC could cause cytotoxicity and oxidative stress in SH-SY5Y cells. Additionally we found uBC initiated progressive development of Alzheimer's disease (AD) associated features, mainly including neuro-inflammation and phosphorylation of tau protein (p-Tau) accumulation. Meanwhile, autophagy process was activated by uBC probably through phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) pathway. RNA interference and autophagosome-lysosome fusion inhibitor were applied to block autophagy process at different stages. Autophagy dysfunction at the initial membrane expansion stage could aggravate p-Tau accumulation and other Alzheimer-like changes in SH-SY5Y cells promoted by uBC. However, autophagy inhibition at the final stage could alleviate p-Tau accumulation caused by uBC. This suggested that inhibition of the infusion of autophagosome and lysosome could possibly activate ubiquitination degradation pathway to regulate p-Tau equilibrium in SH-SY5Y cells. Our findings further raise the concerns about the effects of uBC on the risk of AD and indicate potential roles of autophagy in early Alzheimer-like pathogenic changes caused by ambient uBC. (C) 2018 Elsevier Ltd. All rights reserved.
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