Age-related miRNAs dysregulation and abnormal BACE1 expression following Pb exposure in adolescent mice

被引:4
|
作者
Wang, Ruike [1 ,2 ]
Wu, Zuntao [1 ]
Liu, Rundong [1 ,2 ]
Bai, Lin [1 ,2 ]
Lin, Yan [3 ]
Ba, Yue [1 ,2 ]
Huang, Hui [1 ,2 ]
机构
[1] Zhengzhou Univ, Coll Publ Hlth, Dept Environm Hlth, 100 Kexue Ave, Zhengzhou 450001, Henan, Peoples R China
[2] Zhengzhou Univ, Coll Publ Hlth, Environm & Hlth Innovat Team, Zhengzhou, Peoples R China
[3] Duke Univ, Nicholas Sch Environm, Durham, NC 27708 USA
基金
中国国家自然科学基金;
关键词
aging mice; Alzheimer's disease; lead; miR-124-3p; beta-Site APP-cleaving enzyme 1; ALZHEIMERS-DISEASE; BETA-SECRETASE; INFANTILE EXPOSURE; LEAD PB; A-BETA; MICRORNA; TARGET; BRAIN;
D O I
10.1002/tox.23536
中图分类号
X [环境科学、安全科学];
学科分类号
08 ; 0830 ;
摘要
Numbers of emerging evidence suggest that lead (Pb) exposure contributes to cognitive decline and might also increase the risk of Alzheimer's disease (AD) dementia in the elderly by increasing the beta-amyloid burden. Here, we aimed to characterize the effects of Pb on the post-transcriptional regulators, microRNAs (miRNAs), which may participate in AD pathogenesis. At first, early chronic Pb exposure on neuronal miRNAs expression with increasing aging was profiled to elucidate the association of three selected miRNAs with beta-site APP-cleaving enzyme 1(BACE1), a rate-limiting enzyme for beta-amyloid (A beta) production. Next, we verified changes in BACE1 were observed by regulating miRNAs expression in vitro. While Pb promoted BACE1 levels, BACE1 levels were reduced in SH-SY5Y cells with miR-124-3p mimic, suggesting for the first time that miR-124-3p/BACE1 pathway modulation is critically involved in Pb-induced AD-like amyloidogenic processing. Findings from this study could provide new insight into the molecular mechanisms of Pb-associated neurodegenerative pathogenesis from an epigenetic perspective.
引用
收藏
页码:1902 / 1913
页数:12
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