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Self‐protective transcriptional alterations in ZF4 cells exposed to Pb(NO 3 ) 2 and AgNO 3
Author(s) -
Liu Guangxing,
Tian Jingjing,
Yin Huancai,
Yin Jian,
Tang Yuguo
Publication year - 2019
Publication title -
journal of biochemical and molecular toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.526
H-Index - 58
eISSN - 1099-0461
pISSN - 1095-6670
DOI - 10.1002/jbt.22408
Subject(s) - downregulation and upregulation , glutathione , pregnane x receptor , cytochrome p450 , microbiology and biotechnology , chemistry , glutathione s transferase , transcription factor , detoxification (alternative medicine) , gene expression , oxidative stress , toxicity , multidrug resistance associated protein 2 , biology , gene , enzyme , transporter , atp binding cassette transporter , biochemistry , nuclear receptor , medicine , alternative medicine , organic chemistry , pathology
In this study, gene expression alterations of phase I to III enzymes, transcription factors, and microRNA (miRNA) in embryonic zebrafish fibroblasts (ZF4) cells after the treatment of Pb(NO 3 ) 2 and AgNO 3 were investigated, to illustrate the possible detoxification pathway of heavy metal ions. It was observed that both metals caused concentration‐dependent death and moderate elevation of oxidative stress in ZF4 cells. In response to such toxicity, upregulation of multidrug resistance protein ( mdr ) 4 and multiresistance‐associated protein ( mrp ) 1 were found. However, enhanced expression of glutathione S‐transferase ( gst ) and cytochrome P450 ( cyp ) 1a could only be detected during the exposure of Pb 2+ . In addition, both metals induced extensive upregulation of pregnane X receptor ( pxr ), but only moderate elevation of E2‐related factor ( nrf2) , while they suppressed the expression of miR‐122 and miR‐126 . In conclusion, Pb 2+ and Ag + shared the same detoxification mechanism including ABC transporters, Pxr, and miRNA in ZF4 cells, which needs further investigation.