Waterborne copper exposure up-regulated lipid deposition through the methylation of GRP78 and PGC1α of grass carp Ctenopharyngodon idella.
Ecotoxicol Environ Saf
; 205: 111089, 2020 Dec 01.
Article
em En
| MEDLINE
| ID: mdl-32810645
ABSTRACT
Early molecular events after the exposure of heavy metals, such as aberrant DNA methylation, suggest that DNA methylation was important in regulating physiological processes for animals and accordingly could be used as environmental biomarkers. In the present study, we found that copper (Cu) exposure increased lipid content and induced the DNA hypermethylation at the whole genome level. Especially, Cu induced hypermethylation of glucose-regulated protein 78 (grp78) and peroxisome proliferator-activated receptor gamma coactivator-1α (pgc1α). CCAAT/enhancer binding protein α (C/EBPα) could bind to the methylated sequence of grp78, whereas C/EBPß could not bind to the methylated sequence of grp78. These synergistically influenced grp78 expression and increased lipogenesis. In contrast, DNA methylation of PGC1α blocked the specific protein 1 (SP1) binding and interfered mitochondrial function. Moreover, Cu increased reactive oxygen species (ROS) production, activated endoplasmic reticulum (ER) stress and damaged mitochondrial function, and accordingly increased lipid deposition. Notably, we found a new toxicological mechanism for Cu-induced lipid deposition at DNA methylation level. The measurement of DNA methylation facilitated the use of these epigenetic biomarkers for the evaluation of environmental risk.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Poluentes Químicos da Água
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Carpas
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Cobre
Limite:
Animals
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article