当前位置： SCI文献检索 > TOXICOLOGY AND APPLIED PHARMACOLOGY期刊下所有文献 > Involvement of DNA hypermethylation in down-regulation of the zinc transporter ZIP8 in cadmium-resistant metallothionein-null cells.

Involvement of DNA hypermethylation in down-regulation of the zinc transporter ZIP8 in cadmium-resistant metallothionein-null cells.

Abstract：

:The Zrt/Irt-related protein 8 (ZIP8) encoded by slc39a8 is now emerging as an important zinc transporter involved in cellular cadmium incorporation. We have previously shown that mRNA and protein levels of ZIP8 were decreased in cadmium-resistant metallothionein-null (A7) cells, leading to a decrease in cadmium accumulation. However, the mechanism by which ZIP8 expression is suppressed in these cells remains to be elucidated. In the present study, we investigated the possibility that epigenetic silencing of the slc39a8 gene by DNA hypermethylation is involved in the down-regulation of ZIP8 expression. A7 cells showed a higher mRNA level of DNA methyltransferase 3b than parental cells. Hypermethylation of the CpG island of the slc39a8 gene was detected in A7 cells. Treatment of A7 cells with 5-aza-deoxycytidine, an inhibitor of DNA methyltransferase, caused demethylation of the CpG island of the slc39a8 gene and enhancement of mRNA and protein levels of ZIP8. In response to the recovery of ZIP8 expression, A7 cells treated with 5-aza-deoxycytidine showed an increase in cadmium accumulation and consequently an increase in sensitivity to cadmium. These results suggest that epigenetic silencing of the slc39a8 gene by DNA hypermethylation plays an important role in the down-regulation of ZIP8 in cadmium-resistant metallothionein-null cells.

journal_name

Toxicol Appl Pharmacol

journal_title

Toxicology and applied pharmacology

authors

Fujishiro H,Okugaki S,Yasumitsu S,Enomoto S,Himeno S

doi

10.1016/j.taap.2009.08.015

subject

Has Abstract

pub_date

2009-12-01 00:00:00

pages

195-201

issue

2

eissn

0041-008X

issn

1096-0333

pii

S0041-008X(09)00351-2

journal_volume

241

pub_type

杂志文章

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