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Abstract
Triclosan (TCS) is widely used in personal care products, and its chronic exposure
leads to severely toxic effects in zebrafish (Danio rerio). PKCα, Nrf2 and p53 are
three important signaling pathways concerned with cell development. Herein, we speculated
on and verified a novel TCS regulatory pathway: (1) TCS acted on GPER (G-protein-coupled
estrogen receptor) to activate MAPK/ERK pathway, further resulting in the expression
changes of protein kinase C (PKC) family; (2) PKC participated in Nrf2 phosphorylation;
(3) The expression of miR-125b was regulated by Nrf2; and (4) The expression changes
of related genes in the PKCs-Nrf2-ARE pathway showed the specificity of zebrafish
tissue and organ. TCS exposure led to down-regulation of the Nrf2 and phosphorylated
Nrf2(Ser40) protein in diencephalon nucleus, stratum marginale and stratum centrale
areas in adult zebrafish brain. The phosphorylated Nrf2(Ser40) was mainly expressed
in PGz area, while it was not the case for Nrf2. Both Nrf2 and phosphorylated Nrf2
were activated by TCS exposure; however, the changing trend of PKCs was opposite to
that of Nrf2 in the liver. Both DAPI staining and Merge images demonstrated that TCS
induced oxidative phosphorylation, and phosphorylated Nrf2 is translocated into the
nucleus as the transcription factor to regulate gene transcription in liver and brain.
Nrf2 over-expression increased accumulation of lipid droplets in yolk, brain and liver,
resulting from the upregulation of pri-miR-125b1, pri-miR-125b3, but not pri-miR-125b2.
These findings reveal the upstream regulation mechanism of miR-125b for TCS-induced
fat-metabolism disorder from the regulatory perspective of the pri-miR-125b promoter
region.