shRNA silencing of AS3MT expression minimizes arsenic methylation capacity of HepG2 cells

被引：66

作者：

Drobna, Zuzana ^{[1
]}

Xing, Weibing

Thomas, David J.

Styblo, Miroslav

机构：

[1] Univ N Carolina, Curriculum Toxicol, Dept Nutr, Chapel Hill, NC 27599 USA

[2] Univ N Carolina, Ctr Environm Med Asthma & Lung Biol, Chapel Hill, NC 27599 USA

[3] US EPA, Natl Hlth & Environm Effects Res Lab, Pharmacokinet Branch, Expt Toxicol Div,Off Res & Dev, Res Triangle Pk, NC 27711 USA

来源：

CHEMICAL RESEARCH IN TOXICOLOGY | 2006年 / 19卷 / 07期

关键词：

D O I：

10.1021/tx060076u

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Several methyltransferases have been shown to catalyze the oxidative methylation of inorganic arsenic (iAs) in mammalian species. However, the relative contributions of these enzymes to the overall capacity of cells to methylate iAs have not been characterized. Arsenic (+3 oxidation state) methyltransferase (AS3MT) that is expressed in rat and human hepatocytes catalyzes the conversion of iAs, yielding methylated metabolites that contain arsenic in +3 or +5 oxidation states. This study used short hairpin RNA (shRNA) to knock down AS3MT expression in human hepatocellular carcinoma (HepG2) cells. In a stable clonal HepG2/A cell line, AS3MT mRNA and protein levels were reduced by 83 and 88%, respectively. In comparison, the capacity to methylate iAs decreased only by 70%. These data suggest that AS3MT is the major enzyme in this pathway, although an AS3MT-independent process may contribute to iAs methylation in human hepatic cells.

引用

页码：894 / 898

页数：5

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