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Latent role of in vitro Pb exposure in blocking Aβ clearance and triggering epigenetic modifications.

Abstract：

:Both β-amyloid (Aβ) catabolism and epigenetic regulation play critical roles in the onset of neurodegeneration. The latter also contribute to Pb neurotoxicity. The present study explored the role of epigenetic modifiers and Aβ degradation enzymes in Pb-induced latent effects on Aβ overproduction in vitro. Our results indicated that in SH-SY5Y cells exposed to Pb, the expression of NEP and IDE remained declined during the recovery period, accompanied with abnormal increase of Aβ1-42 and amyloid oligomer. A disruption of selective global post-translational histone modifiers including the decrease of H3K9ac and H4K12ac and the induction of H3K9me2 and H3K27me2 dose dependently was also showed in recovery cells. Moreover, histone deacetylase inhibitor VPA could attenuate latent Aβ accumulation and HDAC activity induced by Pb, which might be by regulating the expression of NEP and IDE epigenetically. Overall, our results suggest sustained reduction of NEP and IDE expression in response to Pb sensitizes recovery SH-SY5Y cells to Aβ accumulation; however, administration of VPA is demonstrated to be beneficial in modulating Aβ clearance.

journal_name

Environ Toxicol Pharmacol

journal_title

Environmental toxicology and pharmacology

authors

Wang Y,Hu Y,Wu Z,Su Y,Ba Y,Zhang H,Li X,Cheng X,Li W,Huang H

doi

10.1016/j.etap.2018.12.015

subject

Has Abstract

pub_date

2019-02-01 00:00:00

pages

14-23

eissn

1382-6689

issn

1872-7077

pii

S1382-6689(18)30578-7

journal_volume

66

pub_type

杂志文章

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