1. Effects of PM2.5 exposure in utero on heart injury, histone acetylation and GATA4 expression in offspring mice.
- Author
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Li, Ruijin, Zhao, Yufei, Shi, Jing, Zhao, Chao, Xie, Peisi, Huang, Wei, Yong, Ting, and Cai, Zongwei
- Subjects
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HISTONE acetylation , *HEART injuries , *HISTONE acetyltransferase , *HEART disease related mortality , *FETAL heart , *HISTONES , *IRON supplements - Abstract
Atmospheric fine particulate matter exposure (PM 2.5) can increase the incidence and mortality of heart disease, and raise the risk of fetal congenital heart defect, which have recently drawn much attention. In this study, C57BL/6 mice were exposed to PM 2.5 (approximately equivalent to 174 μg/m3) by intratracheal instillation during the gestation. After birth, 10 weeks old offspring mice were divided into four groups: male exposed group (ME), female exposed group (FE), male control group (MC), female control group (FC). The pathological injury, pro-inflammatory cytokines, histone acetylation levels, and expressions of GATA-binding protein 4 (GATA4) and downstream genes were investigated. The results showed that exposure to PM 2.5 in utero increased pathological damage and TNF-α and IL-6 levels in hearts of offspring mice, and effects in ME were more serious than FE. Notably, GATA4 protein levels in hearts in ME were significantly lower than that of MC, accompanied by down-regulation of histone acetyltransferase (HAT)-p300 and up-regulation of histone deacetylase-SIRT3. As GATA4 downstream genes, ratios of β-MHC gene expression to α-MHC significantly raised in ME relative to the MC. Results of chromatin immunoprecipitation (ChIP)-qPCR assay found that binding levels of acetylated histone 3 lysine 9 (H3K9ac) in GATA4 promoter region in the hearts of ME or FE were markedly decreased compared with their corresponding control groups. It suggested that maternal exposure to PM 2.5 may cause cardiac injury in the offspring, heart damage of male mice was worse than female mice, in which process HAT-p300, H3K9ac, transcription factor GATA4 may play an important regulation role. Image 1 • PM 2.5 exposure in utero caused heart injury and inflammation in offspring mice. • GATA4 expression decline along with p300 down-regulation and SIRT3 up-regulation. • Binding levels of H3K9ac in GATA4 promoter region were related to GATA4 expression. • Gender differences of mouse heart damage after PM 2.5 exposure in utero exist. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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